Publications

2022

  • [DOI] E. Rossi, G. Leccese, V. Baldelli, A. Bibi, E. Scalone, C. Camilloni, M. Paroni, and P. Landini, “Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain,” Microorganisms, vol. 10, iss. 3, p. 537, 2022.
    [Bibtex] 
    @article{Rossi.2022,
year = {2022},
title = {{Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain}},
author = {Rossi, Elio and Leccese, Gabriella and Baldelli, Valerio and Bibi, Alessia and Scalone, Emanuele and Camilloni, Carlo and Paroni, Moira and Landini, Paolo},
journal = {Microorganisms},
doi = {10.3390/microorganisms10030537},
abstract = {{In Crohn’s disease (CD) patients, the adherent-invasive Escherichia coli (AIEC) pathovar contributes to the chronic inflammation typical of the disease via its ability to invade gut epithelial cells and to survive in macrophages. We show that, in the AIEC strain LF82, inactivation of the pyrD gene, encoding dihydroorotate dehydrogenase (DHOD), an enzyme of the de novo pyrimidine biosynthetic pathway, completely abolished its ability of to grow in a macrophage environment-mimicking culture medium. In addition, pyrD inactivation reduced flagellar motility and strongly affected biofilm formation by downregulating transcription of both type 1 fimbriae and curli subunit genes. Thus, the pyrD gene appears to be essential for several cellular processes involved in AIEC virulence. Interestingly, vidofludimus (VF), a DHOD inhibitor, has been proposed as an effective drug in CD treatment. Despite displaying a potentially similar binding mode for both human and E. coli DHOD in computational molecular docking experiments, VF showed no activity on either growth or virulence-related processes in LF82. Altogether, our results suggest that the crucial role played by the pyrD gene in AIEC virulence, and the presence of structural differences between E. coli and human DHOD allowing for the design of specific inhibitors, make E. coli DHOD a promising target for therapeutical strategies aiming at counteracting chronic inflammation in CD by acting selectively on its bacterial triggers.}},
pages = {537},
number = {3},
volume = {10},
local-url = {file://localhost/Users/elioros/Downloads/microorganisms-10-00537-v3.pdf}
}
  • [DOI] E. Rossi, M. Ghoul, and R. L. Rosa, “Editorial: Pseudomonas aeruginosa Pathogenesis: Virulence, Antibiotic Tolerance and Resistance, Stress Responses and Host-Pathogen Interactions,” Frontiers in cellular and infection microbiology, vol. 12, p. 860314, 2022.
    [Bibtex] 
    @article{10.3389/fcimb.2022.860314,
year = {2022},
title = {{Editorial: Pseudomonas aeruginosa Pathogenesis: Virulence, Antibiotic Tolerance and Resistance, Stress Responses and Host-Pathogen Interactions}},
author = {Rossi, Elio and Ghoul, Melanie and Rosa, Ruggero La},
journal = {Frontiers in Cellular and Infection Microbiology},
doi = {10.3389/fcimb.2022.860314},
pmid = {35242722},
pmcid = {PMC8886208},
pages = {860314},
volume = {12}
}
  • [DOI] D. Carcione, G. Leccese, G. Conte, E. Rossi, J. Intra, A. Bonomi, S. Sabella, M. Moreo, P. Landini, M. Brilli, and M. Paroni, “Lack of Direct Correlation between Biofilm Formation and Antimicrobial Resistance in Clinical Staphylococcus epidermidis Isolates from an Italian Hospital,” Microorganisms, vol. 10, iss. 6, p. 1163, 2022.
    [Bibtex] 
    @article{10.3390/microorganisms10061163,
year = {2022},
title = {{Lack of Direct Correlation between Biofilm Formation and Antimicrobial Resistance in Clinical Staphylococcus epidermidis Isolates from an Italian Hospital}},
author = {Carcione, Davide and Leccese, Gabriella and Conte, Gianmarco and Rossi, Elio and Intra, Jari and Bonomi, Alice and Sabella, Simona and Moreo, Massimo and Landini, Paolo and Brilli, Matteo and Paroni, Moira},
journal = {Microorganisms},
issn = {2076-2607},
doi = {10.3390/microorganisms10061163},
pmid = {35744681},
pmcid = {PMC9230108},
abstract = {{Staphylococcus epidermidis is an opportunistic pathogen and a frequent cause of nosocomial infections. In this work, we show that, among 51 S. epidermidis isolates from an Italian hospital, only a minority displayed biofilm formation, regardless of their isolation source (peripheral blood, catheter, or skin wounds); however, among the biofilm-producing isolates, those from catheters were the most efficient in biofilm formation. Interestingly, most isolates including strong biofilm producers displayed production levels of PIA (polysaccharide intercellular adhesin), the main S. epidermidis extracellular polysaccharide, similar to reference S. epidermidis strains classified as non-biofilm formers, and much lower than those classified as intermediate or high biofilm formers, possibly suggesting that high levels of PIA production do not confer a particular advantage for clinical isolates. Finally, while for the reference S. epidermidis strains the biofilm production clearly correlated with the decreased sensitivity to antibiotics, in particular, protein synthesis inhibitors, in our clinical isolates, such positive correlation was limited to tetracycline. In contrast, we observed an inverse correlation between biofilm formation and the minimal inhibitory concentrations for levofloxacin and teicoplanin. In addition, in growth conditions favoring PIA production, the biofilm-forming isolates showed increased sensitivity to daptomycin, clindamycin, and erythromycin, with increased tolerance to the trimethoprim/sulfamethoxazole association. The lack of direct correlation between the biofilm production and increased tolerance to antibiotics in S. epidermidis isolates from a clinical setting would suggest, at least for some antimicrobials, the possible existence of a trade-off between the production of biofilm determinants and antibiotic resistance.}},
pages = {1163},
number = {6},
volume = {10}
}

2021

  • [DOI] E. Rossi, R. L. Rosa, J. A. Bartell, R. L. Marvig, J. A. J. Haagensen, L. M. Sommer, S. Molin, and H. K. Johansen, “Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis,” Nature reviews microbiology, vol. 19, iss. 5, p. 331–342, 2021.
    [Bibtex] 
    @article{Rossi.2021,
year = {2021},
title = {{Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis}},
author = {Rossi, Elio and Rosa, Ruggero La and Bartell, Jennifer A. and Marvig, Rasmus L. and Haagensen, Janus A. J. and Sommer, Lea M. and Molin, Søren and Johansen, Helle Krogh},
journal = {Nature Reviews Microbiology},
issn = {1740-1526},
doi = {10.1038/s41579-020-00477-5},
pmid = {33214718},
abstract = {{Intense genome sequencing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) airways has shown inefficient eradication of the infecting bacteria, as well as previously undocumented patient-to-patient transmission of adapted clones. However, genome sequencing has limited potential as a predictor of chronic infection and of the adaptive state during infection, and thus there is increasing interest in linking phenotypic traits to the genome sequences. Phenotypic information ranges from genome-wide transcriptomic analysis of patient samples to determination of more specific traits associated with metabolic changes, stress responses, antibiotic resistance and tolerance, biofilm formation and slow growth. Environmental conditions in the CF lung shape both genetic and phenotypic changes of P. aeruginosa during infection. In this Review, we discuss the adaptive and evolutionary trajectories that lead to early diversification and late convergence, which enable P. aeruginosa to succeed in this niche, and we point out how knowledge of these biological features may be used to guide diagnosis and therapy. Pseudomonas aeruginosa shows high diversity and plasticity, which enables it to succeed in the challenging environment of cystic fibrosis airways. In this Review, Johansen and colleagues highlight genomic and phenotypic adaptation of P. aeruginosa and the implications for infection management.}},
pages = {331--342},
number = {5},
volume = {19},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-Pseudomonas%20aeruginosa%20adaptation%20and%20evolution%20in%20patients%20with%20cystic%20fibrosis-2020-Nature%20Reviews%20Microbiology.pdf}
}
  • [DOI] A. Bertocchi, S. Carloni, P. S. Ravenda, G. Bertalot, I. Spadoni, A. L. Cascio, S. Gandini, M. Lizier, D. Braga, F. Asnicar, N. Segata, C. Klaver, P. Brescia, E. Rossi, A. Anselmo, S. Guglietta, A. Maroli, P. Spaggiari, N. Tarazona, A. Cervantes, S. Marsoni, L. Lazzari, M. G. Jodice, C. Luise, M. Erreni, S. Pece, P. P. D. Fiore, G. Viale, A. Spinelli, C. Pozzi, G. Penna, and M. Rescigno, “Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver,” Cancer cell, vol. 39, iss. 5, p. 708–724.e11, 2021.
    [Bibtex] 
    @article{Bertocchi.2021,
year = {2021},
title = {{Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver}},
author = {Bertocchi, Alice and Carloni, Sara and Ravenda, Paola Simona and Bertalot, Giovanni and Spadoni, Ilaria and Cascio, Antonino Lo and Gandini, Sara and Lizier, Michela and Braga, Daniele and Asnicar, Francesco and Segata, Nicola and Klaver, Chris and Brescia, Paola and Rossi, Elio and Anselmo, Achille and Guglietta, Silvia and Maroli, Annalisa and Spaggiari, Paola and Tarazona, Noelia and Cervantes, Andres and Marsoni, Silvia and Lazzari, Luca and Jodice, Maria Giovanna and Luise, Chiara and Erreni, Marco and Pece, Salvatore and Fiore, Pier Paolo Di and Viale, Giuseppe and Spinelli, Antonino and Pozzi, Chiara and Penna, Giuseppe and Rescigno, Maria},
journal = {Cancer Cell},
issn = {1535-6108},
doi = {10.1016/j.ccell.2021.03.004},
pmid = {33798472},
abstract = {{Metastasis is facilitated by the formation of a “premetastatic niche,” which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases.}},
pages = {708--724.e11},
number = {5},
volume = {39},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/pdf.sciencedirectassets.com%2001042021,%20184553.pdf}
}
  • [DOI] R. L. Rosa, E. Rossi, A. M. Feist, H. K. Johansen, and S. Molin, “Compensatory evolution of Pseudomonas aeruginosa’s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis,” Nature communications, vol. 12, iss. 1, p. 3186, 2021.
    [Bibtex] 
    @article{Rosa.2021,
year = {2021},
rating = {4},
title = {{Compensatory evolution of Pseudomonas aeruginosa’s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis}},
author = {Rosa, Ruggero La and Rossi, Elio and Feist, Adam M. and Johansen, Helle Krogh and Molin, Søren},
journal = {Nature Communications},
doi = {10.1038/s41467-021-23451-y},
abstract = {{Long-term infection of the airways of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. This reduction has been hypothesised to increase within-patient fitness and overall persistence of the pathogen. Here, we apply adaptive laboratory evolution to revert the slow growth phenotype of P. aeruginosa clinical strains back to a high growth rate. We identify several evolutionary trajectories and mechanisms leading to fast growth caused by transcriptional and mutational changes, which depend on the stage of adaptation of the strain. Return to high growth rate increases antibiotic susceptibility, which is only partially dependent on reversion of mutations or changes in the transcriptional profile of genes known to be linked to antibiotic resistance. We propose that similar mechanisms and evolutionary trajectories, in reverse direction, may be involved in pathogen adaptation and the establishment of chronic infections in the antibiotic-treated airways of cystic fibrosis patients. Long-term infection of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. Here, La Rosa et al. use adaptive laboratory evolution to increase the growth rate of clinical isolates, and identify mechanisms and evolutionary trajectories that, in reverse direction, may help the pathogen to adapt to the patients’ airways.}},
pages = {3186},
number = {1},
volume = {12},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rosa-Compensatory%20evolution%20of%20Pseudomonas%20aeruginosa’s%20slow%20growth%20phenotype%20suggests%20mechanisms%20of%20adaptation%20in%20cystic%20fibrosis-2021-Nature%20Communications.pdf}
}

2019

  • [DOI] E. B. Burgener, J. M. Sweere, M. S. Bach, P. R. Secor, N. Haddock, L. K. Jennings, R. L. Marvig, H. K. Johansen, E. Rossi, X. Cao, L. Tian, L. Nedelec, S. Molin, P. L. Bollyky, and C. E. Milla, “Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis,” Science translational medicine, vol. 11, iss. 488, p. eaau9748, 2019.
    [Bibtex] 
    @article{Burgener.2019,
year = {2019},
title = {{Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis}},
author = {Burgener, Elizabeth B. and Sweere, Johanna M. and Bach, Michelle S. and Secor, Patrick R. and Haddock, Naomi and Jennings, Laura K. and Marvig, Rasmus L. and Johansen, Helle Krogh and Rossi, Elio and Cao, Xiou and Tian, Lu and Nedelec, Laurence and Molin, Søren and Bollyky, Paul L. and Milla, Carlos E.},
journal = {Science Translational Medicine},
issn = {1946-6234},
doi = {10.1126/scitranslmed.aau9748},
pmid = {30996083},
abstract = {{Filamentous bacteriophage (Pf phage) contribute to the virulence of Pseudomonas aeruginosa infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.5\% (n = 9) were consistently Pf phage positive. In the second cohort, a prospective cross-sectional cohort of 58 patients with CF at Stanford, sputum qPCR analysis showed that 36.2\% (n = 21) of patients were Pf phage positive. In both cohorts, patients positive for Pf phage were older, and in the Stanford CF cohort, patients positive for Pf phage were more likely to have chronic P. aeruginosa infection and had greater declines in pulmonary function during exacerbations than patients negative for Pf phage presence in the sputum. Last, P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics. Mechanistically, in vitro analysis showed that Pf phage sequesters these same antibiotics, suggesting that this mechanism may thereby contribute to the selection of antibiotic resistance over time. These data provide evidence that Pf phage may contribute to clinical outcomes in P. aeruginosa infection in CF.}},
pages = {eaau9748},
number = {488},
volume = {11},
keywords = {},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Burgener-Filamentous%20bacteriophages%20are%20associated%20with%20chronic%20Pseudomonas%20lung%20infections%20and%20antibiotic%20resistance%20in%20cystic%20fibrosis-2019-Science%20Translational%20Medicine.pdf}
}

2018

  • [DOI] M. Falcone, S. Ferrara, E. Rossi, H. K. Johansen, S. Molin, and G. Bertoni, “The Small RNA ErsA of Pseudomonas aeruginosa Contributes to Biofilm Development and Motility through Post-transcriptional Modulation of AmrZ,” Frontiers in microbiology, vol. 9, p. 238, 2018.
    [Bibtex] 
    @article{Falcone.2018,
year = {2018},
rating = {0},
title = {{The Small RNA ErsA of Pseudomonas aeruginosa Contributes to Biofilm Development and Motility through Post-transcriptional Modulation of AmrZ}},
author = {Falcone, Marilena and Ferrara, Silvia and Rossi, Elio and Johansen, Helle K. and Molin, Søren and Bertoni, Giovanni},
journal = {Frontiers in Microbiology},
doi = {10.3389/fmicb.2018.00238},
pmid = {29497413},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2018.00238/full},
abstract = {{The small RNA ErsA of Pseudomonas aeruginosa was previously suggested to be involved in biofilm formation via negative post-transcriptional regulation of the algC gene that encodes the virulence-associated enzyme AlgC, which provides sugar precursors for the synthesis of several polysaccharides. In this study, we show that a knock-out ersA mutant strain forms a flat and uniform biofilm, not characterized by mushroom-multicellular structures typical of a mature biofilm. Conversely, the knock-out mutant strain showed enhanced swarming and twitching motilities. To assess the influence of ErsA on the P. aeruginosa transcriptome, we performed RNA-seq experiments comparing the knock-out mutant with the wild-type. More than 160 genes were found differentially expressed in the knock-out mutant. Parts of these genes, important for biofilm formation and motility regulation, are known to belong also to the AmrZ transcriptional regulator regulon. Here, we show that ErsA binds in vitro and positively regulates amrZ mRNA at post-transcriptional level in vivo suggesting an interesting contribution of the ErsA-amrZ mRNA interaction in biofilm development at several regulatory levels.}},
pages = {238},
volume = {9},
language = {English},
keywords = {},
month = {02},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Falcone-2018-Frontiers%20Microbiol.pdf}
}
  • [DOI] E. Rossi, M. Falcone, S. Molin, and H. K. Johansen, “High-resolution in situ transcriptomics of Pseudomonas aeruginosa unveils genotype independent patho-phenotypes in cystic fibrosis lungs,” Nature communications, vol. 9, iss. 1, p. 3459, 2018.
    [Bibtex] 
    @article{Rossi.2018wcti,
year = {2018},
title = {{High-resolution in situ transcriptomics of Pseudomonas aeruginosa unveils genotype independent patho-phenotypes in cystic fibrosis lungs}},
author = {Rossi, Elio and Falcone, Marilena and Molin, Søren and Johansen, Helle Krogh},
journal = {Nature Communications},
doi = {10.1038/s41467-018-05944-5},
pmid = {30150613},
abstract = {{Life-long bacterial infections in cystic fibrosis (CF) airways constitute an excellent model both for persistent infections and for microbial adaptive evolution in complex dynamic environments. Using high-resolution transcriptomics applied on CF sputum, we profile transcriptional phenotypes of Pseudomonas aeruginosa populations in patho-physiological conditions. Here we show that the soft-core genome of genetically distinct populations, while maintaining transcriptional flexibility, shares a common expression program tied to the lungs environment. We identify genetically independent traits defining P. aeruginosa physiology in vivo, documenting the connection between several previously identified mutations in CF isolates and some of the convergent phenotypes known to develop in later stages of the infection. In addition, our data highlight to what extent this organism can exploit its extensive repertoire of physiological pathways to acclimate to a new niche and suggest how alternative nutrients produced in the lungs may be utilized in unexpected metabolic contexts. How genetic adaptation and phenotypic acclimation are interrelated and allow Pseudomonas aeruginosa to persist in cystic fibrosis lungs is poorly understood. Here, Rossi et al. use high-resolution transcriptomics on expectorates to link phenotypic conservation to ecological flexibility and persistence.}},
pages = {3459},
number = {1},
volume = {9},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-2018-Nat%20Commun.pdf}
}
  • [DOI] J. Frimodt-Møller, E. Rossi, J. A. J. Haagensen, M. Falcone, S. Molin, and H. K. Johansen, “Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts,” Scientific reports, vol. 8, iss. 1, p. 12512, 2018.
    [Bibtex] 
    @article{Frimodt-Møller.2018,
year = {2018},
title = {{Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts}},
author = {Frimodt-Møller, Jakob and Rossi, Elio and Haagensen, Janus Anders Juul and Falcone, Marilena and Molin, Søren and Johansen, Helle Krogh},
journal = {Scientific Reports},
doi = {10.1038/s41598-018-30972-y},
pmid = {30131514},
abstract = {{In 474 genome sequenced Pseudomonas aeruginosa isolates from 34 cystic fibrosis (CF) patients, 40\% of these harbor mutations in the mexZ gene encoding a negative regulator of the MexXY-OprM efflux pump associated with aminoglycoside and fluoroquinolone resistance. Surprisingly, resistance to aminoglycosides and fluoroquinolones of mexZ mutants was far below the breakpoint of clinical resistance. However, the fitness increase of the mutant bacteria in presence of the relevant antibiotics, as demonstrated in competition experiments between mutant and ancestor bacteria, showed that 1) very small phenotypic changes cause significant fitness increase with severe adaptive consequences, and 2) standardized phenotypic tests fail to detect such low-level variations. The frequent appearance of P. aeruginosa mexZ mutants in CF patients is directly connected to the intense use of the target antibiotics, and low-level antibiotic resistance, if left unnoticed, can result in accumulation of additional genetic changes leading to high-level resistance.}},
pages = {12512},
number = {1},
volume = {8},
keywords = {},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Frimodt-Møller-2018-Sci%20Rep-uk.pdf}
}
  • [DOI] E. Rossi, M. Paroni, and P. Landini, “Biofilm and motility in response to environmental and host‐related signals in Gram negative opportunistic pathogens,” Journal of applied microbiology, vol. 125, iss. 6, p. 1587–1602, 2018.
    [Bibtex] 
    @article{Rossi.2018,
year = {2018},
title = {{Biofilm and motility in response to environmental and host‐related signals in Gram negative opportunistic pathogens}},
author = {Rossi, E. and Paroni, M. and Landini, P.},
journal = {Journal of Applied Microbiology},
issn = {1364-5072},
doi = {10.1111/jam.14089},
pmid = {30153375},
abstract = {{Most bacteria can switch between a planktonic, sometimes motile, form and a biofilm mode, in which bacterial cells can aggregate and attach to a solid surface. The transition between these two forms represents an example of bacterial adaptation to environmental signals and stresses. In ‘environmental pathogens’, namely, environmental bacteria that are also able to cause disease in animals and humans, signals associated either with the host or with the external environment, such as temperature, oxygen availability, nutrient concentrations etc., play a major role in triggering the switch between the motile and the biofilm mode, via complex regulatory mechanisms that control flagellar synthesis and motility, and production of adhesion factors. In this review article, we present examples of how environmental signals can impact biofilm formation and cell motility in the Gram negative bacteria Pseudomonas aeruginosa, Escherichia coli and in the Burkholderia genus, and how the switch between motile and biofilm mode can be an essential part of a more general process of adaptation either to the host or to the external environment.}},
pages = {1587--1602},
number = {6},
volume = {125},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-Biofilm%20and%20motility%20in%20response%20to%20environmental%20and%20host‐related%20signals%20in%20Gram%20negative%20opportunistic%20pathogens-2018-Journal%20of%20Applied%20Microbiology.pdf}
}

2017

  • [DOI] E. Rossi, S. Motta, A. Aliverti, F. Cossu, L. Gourlay, P. Mauri, and P. Landini, “Cellulose production is coupled to sensing of the pyrimidine biosynthetic pathway via c‐di‐GMP production by the DgcQ protein of Escherichia coli,” Environmental microbiology, vol. 19, iss. 11, p. 4551–4563, 2017.
    [Bibtex] 
    @article{Rossi.2017x1l,
year = {2017},
title = {{Cellulose production is coupled to sensing of the pyrimidine biosynthetic pathway via c‐di‐GMP production by the DgcQ protein of Escherichia coli}},
author = {Rossi, Elio and Motta, Sara and Aliverti, Alessandro and Cossu, Federica and Gourlay, Louise and Mauri, Pierluigi and Landini, Paolo},
journal = {Environmental Microbiology},
issn = {1462-2920},
doi = {10.1111/1462-2920.13918},
pmid = {28892259},
abstract = {{Production of cellulose, a stress response-mediated process in enterobacteria, is modulated in Escherichia coli by the activity of the two pyrimidine nucleotide biosynthetic pathways, namely, the de novo biosynthetic pathway and the salvage pathway, which relies on the environmental availability of pyrimidine nitrogenous bases. We had previously reported that prevalence of the salvage over the de novo pathway triggers cellulose production via synthesis of the second messenger c-di-GMP by the DgcQ (YedQ) diguanylate cyclase. In this work, we show that DgcQ enzymatic activity is enhanced by UTP, whilst being inhibited by N-carbamoyl-aspartate, an intermediate of the de novo pathway. Thus, direct allosteric control by these ligands allows full DgcQ activity exclusively in cells actively synthesizing pyrimidine nucleotides via the salvage pathway. Inhibition of DgcQ activity by N-carbamoyl-aspartate appears to be favoured by protein-protein interaction between DgcQ and PyrB, a subunit of aspartate transcarbamylase, which synthesizes N-carbamoyl-aspartate. Our results suggest that availability of pyrimidine bases might be sensed, somehow paradoxically, as an environmental stress by E. coli. We hypothesize that this link might have evolved since stress events, leading to extensive DNA/RNA degradation or lysis of neighbouring cells, can result in increased pyrimidine concentrations and activation of the salvage pathway.}},
pages = {4551--4563},
number = {11},
volume = {19},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-Cellulose%20production%20is%20coupled%20to%20sensing%20of%20the%20pyrimidine%20biosynthetic%20pathway%20via%20c‐di‐GMP%20production%20by%20the%20DgcQ%20protein%20of%20Escherichia%20coli-2017-Environmental%20Microbiology_1.pdf}
}
  • [DOI] E. Rossi, A. Cimdins, P. Lüthje, A. Brauner, Å. Sjöling, P. Landini, and U. Römling, ““It’s a gut feeling” – Escherichia coli biofilm formation in the gastrointestinal tract environment,” Critical reviews in microbiology, vol. 44, iss. 1, p. 1–30, 2017.
    [Bibtex] 
    @article{Rossi.2017,
year = {2017},
title = {{“It’s a gut feeling” – Escherichia coli biofilm formation in the gastrointestinal tract environment}},
author = {Rossi, Elio and Cimdins, Annika and Lüthje, Petra and Brauner, Annelie and Sjöling, Åsa and Landini, Paolo and Römling, Ute},
journal = {Critical Reviews in Microbiology},
issn = {1040-841X},
doi = {10.1080/1040841x.2017.1303660},
pmid = {28485690},
abstract = {{Escherichia coli can commonly be found, either as a commensal, probiotic or a pathogen, in the human gastrointestinal (GI) tract. Biofilm formation and its regulation is surprisingly variable, although distinct regulatory pattern of red, dry and rough (rdar) biofilm formation arise in certain pathovars and even clones. In the GI tract, environmental conditions, signals from the host and from commensal bacteria contribute to shape E. coli biofilm formation within the multi-faceted multicellular communities in a complex and integrated fashion. Although some major regulatory networks, adhesion factors and extracellular matrix components constituting E. coli biofilms have been recognized, these processes have mainly been characterized in vitro and in the context of interaction of E. coli strains with intestinal epithelial cells. However, direct observation of E. coli cells in situ, and the vast number of genes encoding surface appendages on the core or accessory genome of E. coli suggests the complexity of the biofilm process to be far from being fully understood. In this review, we summarize biofilm formation mechanisms of commensal, probiotic and pathogenic E. coli in the context of the gastrointestinal tract.}},
pages = {1--30},
number = {1},
volume = {44},
keywords = {},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-2017-Critical%20Reviews%20in%20Microbiology.pdf}
}

2016

  • [DOI] E. Rossi, F. Longo, M. Barbagallo, C. Peano, C. Consolandi, A. Pietrelli, S. Jaillon, C. Garlanda, and P. Landini, “Glucose availability enhances lipopolysaccharide production and immunogenicity in the opportunistic pathogenAcinetobacter baumannii,” Future microbiology, vol. 11, iss. 3, p. 335–349, 2016.
    [Bibtex] 
    @article{Rossi.2016,
year = {2016},
rating = {0},
title = {{Glucose availability enhances lipopolysaccharide production and immunogenicity in the opportunistic pathogenAcinetobacter baumannii}},
author = {Rossi, Elio and Longo, Francesca and Barbagallo, Marialuisa and Peano, Clelia and Consolandi, Clarissa and Pietrelli, Alessandro and Jaillon, Sebastian and Garlanda, Cecilia and Landini, Paolo},
journal = {Future Microbiology},
issn = {1746-0913},
doi = {10.2217/fmb.15.153},
pmid = {26934424},
abstract = {{Aim: Acinetobacter baumannii can cause sepsis with high mortality rates. We investigated whether glucose sensing might play a role in A. baumannii pathogenesis. Materials \& methods: We carried out transcriptome analysis and extracellular polysaccharide determination in an A. baumannii clinical isolate grown on complex medium with or without glucose supplementation, and assessed its ability to induce production of inflammatory cytokines in human macrophages. Results: Growth in glucose-supplemented medium strongly enhanced A. baumannii sugar anabolism, resulting in increasing lipopolysaccharide biosynthesis. In addition, glucose induced active shedding of lipopolysaccharide, in turn triggering a strong induction of inflammatory cytokines in human macrophages. Finally, hemolytic activity was strongly enhanced by growth in glucose-supplemented medium. Conclusion: We propose that sensing of exogenous glucose might trigger A. baumannii pathogenesis during sepsis.}},
pages = {335--349},
number = {3},
volume = {11},
language = {English},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-Glucose%20availability%20enhances%20lipopolysaccharide%20production%20and%20immunogenicity%20in%20the%20opportunistic%20pathogenAcinetobacter%20baumannii-2016-Future%20Microbiology.pdf}
}
  • [DOI] F. Longo, S. Motta, P. Mauri, P. Landini, and E. Rossi, “Interplay of the modified nucleotide phosphoadenosine 5′-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein,” Chemico-biological interactions, vol. 259, iss. Pt A, p. 39–47, 2016.
    [Bibtex] 
    @article{Longo.2016,
year = {2016},
rating = {0},
title = {{Interplay of the modified nucleotide phosphoadenosine 5′-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein}},
author = {Longo, Francesca and Motta, Sara and Mauri, Pierluigi and Landini, Paolo and Rossi, Elio},
journal = {Chemico-Biological Interactions},
issn = {0009-2797},
doi = {10.1016/j.cbi.2016.04.016},
pmid = {27091548},
abstract = {{In the bacterium Escherichia coli, some intermediates of the sulfate assimilation and cysteine biosynthesis pathway can act as signal molecules and modulate gene expression. In addition to sensing and utilization of sulphur sources, these signaling mechanisms also impact more global cell processes, such as resistance to antimicrobial agents and biofilm formation. In a recent work, we have shown that inactivation of the cysH gene, encoding phosphoadenosine-phosphosulfate (PAPS) reductase, and the consequent increase in intracellular PAPS concentration, strongly affect production of several cell surface-associated structures, enhancing surface adhesion and cell aggregation. In order to identify the molecular mechanism relaying intracellular PAPS concentration to regulation of cell surface-associated structures, we looked for mutations able to suppress the effects of cysH inactivation. We found that mutations in the adenylate cyclase-encoding cyaA gene abolished the effects of PAPS accumulation; consistent with this result, cyclic AMP (cAMP)-dependent gene expression appears to be increased in the cysH mutant. Experiments aimed at the direct identification of proteins interacting with either CysC or CysH, i.e. the PAPS-related proteins APS kinase and PAPS reductase, allowed us to identify several regulators, namely, CspC, CspE, HNS and HupA. Protein-protein interaction between HupA and CysH was confirmed by a bacterial two hybrid system, and inactivation of the hupA gene enhanced the effects of the cysH mutation in terms of production of cell surface-associated factors. Our results indicate that PAPS can modulate different regulatory systems, providing evidence that this molecule acts as a global signal molecule in E. coli.}},
pages = {39--47},
number = {Pt A},
volume = {259},
language = {English},
month = {11},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Longo-Interplay%20of%20the%20modified%20nucleotide%20phosphoadenosine%205′-phosphosulfate%20(PAPS)%20with%20global%20regulatory%20proteins%20in%20Escherichia%20coli-%20modulation%20of%20cyclic%20AMP%20(cAMP)-dependent%20gene%20expression%20and%20interaction%20with%20the%20HupA%20regulatory%20protein-2.pdf}
}
  • [DOI] P. D. Pasquale, M. Caterino, A. D. Somma, M. Squillace, E. Rossi, P. Landini, V. Iebba, S. Schippa, R. Papa, L. Selan, M. Artini, A. Palamara, and A. Duilio, “Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA,” Frontiers in microbiology, vol. 7, p. 147, 2016.
    [Bibtex] 
    @article{Pasquale.2016,
year = {2016},
rating = {0},
title = {{Exposure of E. coli to DNA-Methylating Agents Impairs Biofilm Formation and Invasion of Eukaryotic Cells via Down Regulation of the N-Acetylneuraminate Lyase NanA}},
author = {Pasquale, Pamela Di and Caterino, Marianna and Somma, Angela Di and Squillace, Marta and Rossi, Elio and Landini, Paolo and Iebba, Valerio and Schippa, Serena and Papa, Rosanna and Selan, Laura and Artini, Marco and Palamara, Annateresa and Duilio, Angela},
journal = {Frontiers in Microbiology},
doi = {10.3389/fmicb.2016.00147},
pmid = {26904018},
abstract = {{DNA methylation damage can be induced by endogenous and exogenous chemical agents, which has led every living organism to develop suitable response strategies. We investigated protein expression profiles of Escherichia coli upon exposure to the alkylating agent methyl-methane sulfonate (MMS) by differential proteomics. Quantitative proteomic data showed a massive downregulation of enzymes belonging to the glycolytic pathway and fatty acids degradation, strongly suggesting a decrease of energy production. A strong reduction in the expression of the N-acetylneuraminate lyases (NanA) involved in the sialic acid metabolism was also observed. Using a null NanA mutant and DANA, a substrate analog acting as competitive inhibitor, we demonstrated that down regulation of NanA affects biofilm formation and adhesion properties of E. coli MV1161. Exposure to alkylating agents also decreased biofilm formation and bacterial adhesion to Caco-2 eukaryotic cell line by the adherent invasive E. coli (AIEC) strain LF82. Our data showed that methylation stress impairs E. coli adhesion properties and suggest a possible role of NanA in biofilm formation and bacteria host interactions.}},
pages = {147},
volume = {7},
language = {English}
}

2015

  • [DOI] C. Peano, J. Wolf, J. Demol, E. Rossi, L. Petiti, G. D. Bellis, J. Geiselmann, T. Egli, S. Lacour, and P. Landini, “Characterization of the Escherichia coli σS core regulon by Chromatin Immunoprecipitation-sequencing (ChIP-seq) analysis,” Scientific reports, vol. 5, iss. 1, p. 10469, 2015.
    [Bibtex] 
    @article{Peano.2015,
year = {2015},
rating = {0},
title = {{Characterization of the Escherichia coli σS core regulon by Chromatin Immunoprecipitation-sequencing (ChIP-seq) analysis}},
author = {Peano, Clelia and Wolf, Johannes and Demol, Julien and Rossi, Elio and Petiti, Luca and Bellis, Gianluca De and Geiselmann, Johannes and Egli, Thomas and Lacour, Stephan and Landini, Paolo},
journal = {Scientific Reports},
doi = {10.1038/srep10469},
pmid = {26020590},
pmcid = {PMC4447067},
abstract = {{In bacteria, selective promoter recognition by RNA polymerase is achieved by its association with σ factors, accessory subunits able to direct RNA polymerase “core enzyme” (E) to different promoter sequences. Using Chromatin Immunoprecipitation-sequencing (ChIP-seq), we searched for promoters bound by the σS-associated RNA polymerase form (EσS) during transition from exponential to stationary phase. We identified 63 binding sites for EσS overlapping known or putative promoters, often located upstream of genes (encoding either ORFs or non-coding RNAs) showing at least some degree of dependence on the σS-encoding rpoS gene. EσS binding did not always correlate with an increase in transcription level, suggesting that, at some σS-dependent promoters, EσS might remain poised in a pre-initiation state upon binding. A large fraction of EσS-binding sites corresponded to promoters recognized by RNA polymerase associated with σ70 or other σ factors, suggesting a considerable overlap in promoter recognition between different forms of RNA polymerase. In particular, EσS appears to contribute significantly to transcription of genes encoding proteins involved in LPS biosynthesis and in cell surface composition. Finally, our results highlight a direct role of EσS in the regulation of non coding RNAs, such as OmrA/B, RyeA/B and SibC.}},
pages = {10469},
number = {1},
volume = {5},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Peano-Characterization%20of%20the%20Escherichia%20coli%20σS%20core%20regulon%20by%20Chromatin%20Immunoprecipitation-sequencing%20(ChIP-seq)%20analysis-2015-Scientific%20Reports.pdf}
}

2014

  • [DOI] E. Rossi, S. Motta, P. Mauri, and P. Landini, “Sulfate assimilation pathway intermediate phosphoadenosine 5′-phosphosulfate acts as a signal molecule affecting production of curli fibres in Escherichia coli,” Microbiology, vol. 160, iss. Pt_9, p. 1832–1844, 2014.
    [Bibtex] 
    @article{Rossi.2014,
year = {2014},
rating = {0},
title = {{Sulfate assimilation pathway intermediate phosphoadenosine 5′-phosphosulfate acts as a signal molecule affecting production of curli fibres in Escherichia coli}},
author = {Rossi, Elio and Motta, Sara and Mauri, Pierluigi and Landini, Paolo},
journal = {Microbiology},
issn = {1350-0872},
doi = {10.1099/mic.0.079699-0},
pmid = {24934621},
abstract = {{The enterobacterium Escherichia coli can utilize a variety of molecules as sulfur sources, including cysteine, sulfate, thiosulfate and organosulfonates. An intermediate of the sulfate assimilation pathway, adenosine 5′-phosphosulfate (APS), also acts as a signal molecule regulating the utilization of different sulfur sources. In this work, we show that inactivation of the cysH gene, leading to accumulation of phosphoadenosine 5′-phosphosulfate (PAPS), also an intermediate of the sulfate assimilation pathway, results in increased surface adhesion and cell aggregation by activating the expression of the curli-encoding csgBAC operon. In contrast, curli production was unaffected by the inactivation of any other gene belonging to the sulfate assimilation pathway. Overexpression of the cysH gene downregulated csgBAC transcription, further suggesting a link between intracellular PAPS levels and curli gene expression. In addition to curli components, the Flu, OmpX and Slp proteins were also found in increased amounts in the outer membrane compartment of the cysH mutant; deletion of the corresponding genes suggested that these proteins also contribute to surface adhesion and cell surface properties in this strain. Our results indicate that, similar to APS, PAPS also acts as a signal molecule, albeit with a distinct mechanism and role: whilst APS regulates organosulfonate utilization, PAPS would couple availability of sulfur sources to remodulation of the cell surface, as part of a more global effect on cell physiology.}},
pages = {1832--1844},
number = {Pt\_9},
volume = {160},
language = {English},
keywords = {},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Rossi-Sulfate%20assimilation%20pathway%20intermediate%20phosphoadenosine%205′-phosphosulfate%20acts%20as%20a%20signal%20molecule%20affecting%20production%20of%20curli%20fibres%20in%20Escherichia%20coli-2014-Microbiology.pdf}
}
  • [DOI] C. Peano, F. Chiaramonte, S. Motta, A. Pietrelli, S. Jaillon, E. Rossi, C. Consolandi, O. L. Champion, S. L. Michell, L. Freddi, L. Falciola, F. Basilico, C. Garlanda, P. Mauri, G. D. Bellis, and P. Landini, “Gene and Protein Expression in Response to Different Growth Temperatures and Oxygen Availability in Burkholderia thailandensis,” Plos one, vol. 9, iss. 3, p. e93009, 2014.
    [Bibtex] 
    @article{Peano.2014,
year = {2014},
rating = {0},
title = {{Gene and Protein Expression in Response to Different Growth Temperatures and Oxygen Availability in Burkholderia thailandensis}},
author = {Peano, Clelia and Chiaramonte, Fabrizio and Motta, Sara and Pietrelli, Alessandro and Jaillon, Sebastien and Rossi, Elio and Consolandi, Clarissa and Champion, Olivia L. and Michell, Stephen L. and Freddi, Luca and Falciola, Luigi and Basilico, Fabrizio and Garlanda, Cecilia and Mauri, Pierluigi and Bellis, Gianluca De and Landini, Paolo},
journal = {PLoS ONE},
doi = {10.1371/journal.pone.0093009},
pmid = {24671187},
abstract = {{Burkholderia thailandensis, although normally avirulent for mammals, can infect macrophages in vitro and has occasionally been reported to cause pneumonia in humans. It is therefore used as a model organism for the human pathogen B. pseudomallei, to which it is closely related phylogenetically. We characterized the B. thailandensis clinical isolate CDC2721121 (BtCDC272) at the genome level and studied its response to environmental cues associated with human host colonization, namely, temperature and oxygen limitation. Effects of the different growth conditions on BtCDC272 were studied through whole genome transcription studies and analysis of proteins associated with the bacterial cell surface. We found that growth at 37°C, compared to 28°C, negatively affected cell motility and flagella production through a mechanism involving regulation of the flagellin-encoding fliC gene at the mRNA stability level. Growth in oxygen-limiting conditions, in contrast, stimulated various processes linked to virulence, such as lipopolysaccharide production and expression of genes encoding protein secretion systems. Consistent with these observations, BtCDC272 grown in oxygen limitation was more resistant to phagocytosis and strongly induced the production of inflammatory cytokines from murine macrophages. Our results suggest that, while temperature sensing is important for regulation of B. thailandensis cell motility, oxygen limitation has a deeper impact on its physiology and constitutes a crucial environmental signal for the production of virulence factors.}},
editor = {Morici, Lisa A},
pages = {e93009},
number = {3},
volume = {9},
language = {English},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Peano-Gene%20and%20Protein%20Expression%20in%20Response%20to%20Different%20Growth%20Temperatures%20and%20Oxygen%20Availability%20in%20Burkholderia%20thailandensis-2014-PLoS%20ONE.pdf}
}

2013

  • [DOI] C. Peano, A. Pietrelli, C. Consolandi, E. Rossi, L. Petiti, L. Tagliabue, G. D. Bellis, and P. Landini, “An efficient rRNA removal method for RNA sequencing in GC-rich bacteria,” Microbial informatics and experimentation, vol. 3, iss. 1, p. 1–11, 2013.
    [Bibtex] 
    @article{Peano.2012,
year = {2013},
rating = {0},
title = {{An efficient rRNA removal method for RNA sequencing in GC-rich bacteria}},
author = {Peano, Clelia and Pietrelli, Alessandro and Consolandi, Clarissa and Rossi, Elio and Petiti, Luca and Tagliabue, Letizia and Bellis, Gianluca De and Landini, Paolo},
journal = {Microbial Informatics and Experimentation},
issn = {2042-5783},
doi = {10.1186/2042-5783-3-1},
pmid = {23294941},
abstract = {{Background Next generation sequencing (NGS) technologies have revolutionized gene expression studies and functional genomics analysis. However, further improvement of RNA sequencing protocols is still desirable, in order to reduce NGS costs and to increase its accuracy. In bacteria, a major problem in RNA sequencing is the abundance of ribosomal RNA (rRNA), which accounts for 95-98\% of total RNA and can therefore hinder sufficient coverage of mRNA, the main focus of transcriptomic studies. Thus, efficient removal of rRNA is necessary to achieve optimal coverage, good detection sensitivity and reliable results. An additional challenge is presented by microorganisms with GC-rich genomes, in which rRNA removal is less efficient. Results In this work, we tested two commercial kits for rRNA removal, either alone or in combination, on Burkholderia thailandensis. This bacterium, chosen as representative of the important Burkholderia genus, which includes both pathogenic and environmental bacteria, has a rather large (6.72 Mb) and GC-rich (67.7\%) genome. Each enriched mRNA sample was sequenced through paired-end Illumina GAIIx run in duplicate, yielding between 10 and 40 million reads. We show that combined treatment with both kits allows an mRNA enrichment of more than 238-fold, enabling the sequencing of almost all (more than 90\%) B. thailandensis transcripts from less than 10 million reads, without introducing any bias in mRNA relative abundance, thus preserving differential expression profile. Conclusions The mRNA enrichment protocol presented in this work leads to an increase in detection sensitivity up to 770\% compared to total RNA; such increased sensitivity allows for a corresponding reduction in the number of sequencing reads necessary for the complete analysis of whole transcriptome expression profiling. Thus we can conclude that the MICROBExpress/Ovation combined rRNA removal method could be suitable for RNA sequencing of whole transcriptomes of microorganisms with high GC content and complex genomes enabling at the same time an important scaling down of sequencing costs.}},
pages = {1--11},
number = {1},
volume = {3},
language = {English},
month = {01},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Peano-An%20efficient%20rRNA%20removal%20method%20for%20RNA%20sequencing%20in%20GC-rich%20bacteria-2012-Microbial%20Informatics%20and%20Experimentation.pdf}
}
  • [DOI] D. Antoniani, E. Rossi, S. Rinaldo, P. Bocci, M. Lolicato, A. Paiardini, N. Raffaelli, F. Cutruzzolà, and P. Landini, “The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability,” Applied microbiology and biotechnology, vol. 97, iss. 16, p. 7325–7336, 2013.
    [Bibtex] 
    @article{Antoniani.2013,
year = {2013},
rating = {0},
title = {{The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability}},
author = {Antoniani, Davide and Rossi, Elio and Rinaldo, Serena and Bocci, Paola and Lolicato, Marco and Paiardini, Alessandro and Raffaelli, Nadia and Cutruzzolà, Francesca and Landini, Paolo},
journal = {Applied Microbiology and Biotechnology},
issn = {0175-7598},
doi = {10.1007/s00253-013-4875-0},
pmid = {23584245},
abstract = {{In Gram-negative bacteria, production of the signal molecule c-di-GMP by diguanylate cyclases (DGCs) is a key trigger for biofilm formation, which, in turn, is often required for the development of chronic bacterial infections. Thus, DGCs represent interesting targets for new chemotherapeutic drugs with anti-biofilm activity. We searched for inhibitors of the WspR protein, a Pseudomonas aeruginosa DGC involved in biofilm formation and production of virulence factors, using a set of microbiological assays developed in an Escherichia coli strain expressing the wspR gene. We found that azathioprine, an immunosuppressive drug used in the treatment of Crohn’s disease, was able to inhibit WspR-dependent c-di-GMP biosynthesis in bacterial cells. However, in vitro enzymatic assays ruled out direct inhibition of WspR DGC activity either by azathioprine or by its metabolic derivative 2-amino-6-mercapto-purine riboside. Azathioprine is an inhibitor of 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase, an enzyme involved in purine biosynthesis, which suggests that inhibition of c-di-GMP biosynthesis by azathioprine may be due to perturbation of intracellular nucleotide pools. Consistent with this hypothesis, WspR activity is abolished in an E. coli purH mutant strain, unable to produce AICAR transformylase. Despite its effect on WspR, azathioprine failed to prevent biofilm formation by P. aeruginosa; however, it affected production of extracellular structures in E. coli clinical isolates, suggesting efficient inhibition of c-di-GMP biosynthesis in this bacterium. Our results indicate that azathioprine can prevent biofilm formation in E. coli through inhibition of c-di-GMP biosynthesis and suggest that such inhibition might contribute to its anti-inflammatory activity in Crohn’s disease.}},
pages = {7325--7336},
number = {16},
volume = {97},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Antoniani-2013-Applied%20Microbiology%20and%20Biotechnology.pdf}
}

2012

  • [DOI] M. Garavaglia, E. Rossi, and P. Landini, “The Pyrimidine Nucleotide Biosynthetic Pathway Modulates Production of Biofilm Determinants in Escherichia coli,” Plos one, vol. 7, iss. 2, p. e31252, 2012.
    [Bibtex] 
    @article{Garavaglia.2012,
year = {2012},
rating = {0},
title = {{The Pyrimidine Nucleotide Biosynthetic Pathway Modulates Production of Biofilm Determinants in Escherichia coli}},
author = {Garavaglia, Marco and Rossi, Elio and Landini, Paolo},
journal = {PLoS ONE},
doi = {10.1371/journal.pone.0031252},
pmid = {22359582},
abstract = {{Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions.}},
editor = {Marinus, Martin G},
pages = {e31252},
number = {2},
volume = {7},
language = {English},
keywords = {},
local-url = {file://localhost/Users/elioros/Documents/Papers%20Library/Garavaglia-The%20Pyrimidine%20Nucleotide%20Biosynthetic%20Pathway%20Modulates%20Production%20of%20Biofilm%20Determinants%20in%20Escherichia%20coli-2012-PLoS%20ONE.pdf}
}