Role of Mobile DNA in the Evolution of Vancomycin-Resistant
            <i>Enterococcus faecalis</i>

Paulsen, Ian T.; Banerjei, Linda; Myers, Garry; Nelson, Karen E.; Seshadri, Rekha; Read, Timothy D.; Fouts, Derrick E.; Eisen, Jonathan A.; Gill, Steven R.; Heidelberg, John F.; Tettelin, Hervé; Dodson, Robert J.; Umayam, Lowell; Brinkac, Lauren; Beanan, Mauren; Daugherty, Sean C.; DeBoy, Robert T.; Durkin, Scott; Kolonay, James F.; Madupu, Ramana; Nelson, Will; Vamathevan, Jessica; Tran, Benjamin; Upton, Julia; Hansen, Thomas Arn; Shetty, Jyoti; Khouri, Hoda; Utterback, Terry; Radune, Diana; Ketchum, Karen A.; Dougherty, Brian; Fraser, Claire M.

doi:10.1126/science.1080613

Cited by 841 publications

(857 citation statements)

References 17 publications

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“…Parental E. coli K12 strains were DJ624Dara, 60 MG1655D10, 61 and DH5a (Invitrogen), and E. faecalis strains were V583, and OG1RF. 44,62 Plasmid pCRII-TOPO (Invitrogen) was used for direct cloning of amplicons. Clones were screened with oligos FR.T7 and FR.SP6 (Table S1).…”

Section: Methodsmentioning

confidence: 99%

Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis

et al. 2015

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We discovered a chromosomal locus containing 2 toxin-antitoxin modules (TAs) with an antisense transcriptional organization in the E. faecalis clinical isolate V583. These TAs are homologous to the type I txpA-ratA system and the type II mazEF, respectively. We have shown that the putative MazF is toxic for E. coli and triggers RNA degradation, and its cognate antitoxin MazE counteracts toxicity. The second module, adjacent to mazEF, expresses a toxin predicted to belong to the TxpA type I family found in Firmicutes, and the antisense RNA antidote, RatA. Genomic analysis indicates that the cis-association of mazEF and txpA-ratA modules has been favored during evolution, suggesting a selective advantage for this TA organization in the E. faecalis species. We showed regulatory interplays between the 2 modules, involving transcription control and RNA stability. Remarkably, our data reveal that MazE and MazEF have a dual transcriptional activity: they act as autorepressors and activate ratA transcription, most likely in a direct manner. RatA controls txpA RNA levels through stability. Our data suggest a pivotal role of MazEF in the coordinated expression of mazEF and txpA-ratA modules in V583. To our knowledge, this is the first report describing a crosstalk between type I and II TAs.

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Section: Methodsmentioning

confidence: 99%

Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis

et al. 2015

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“…E. faecalis is normally a benign resident of the gut flora. However, the first vancomycinresistant enterococcal strain had a number of DNA elements, apparently of foreign origin, which comprised a quarter of the genome of that strain (186). These elements included a variety of resistance determinants as well as a pathogenicity island carrying a number of virulence-associated genes.…”

Section: Transition: From Commensal To Pathogenmentioning

confidence: 99%

Bacteroides: the Good, the Bad, and the Nitty-Gritty

2007

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SUMMARY Summary: Bacteroides species are significant clinical pathogens and are found in most anaerobic infections, with an associated mortality of more than 19%. The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites. Genomic and proteomic analyses have vastly added to our understanding of the manner in which Bacteroides species adapt to, and thrive in, the human gut. A few examples are (i) complex systems to sense and adapt to nutrient availability, (ii) multiple pump systems to expel toxic substances, and (iii) the ability to influence the host immune system so that it controls other (competing) pathogens. B. fragilis, which accounts for only 0.5% of the human colonic flora, is the most commonly isolated anaerobic pathogen due, in part, to its potent virulence factors. Species of the genus Bacteroides have the most antibiotic resistance mechanisms and the highest resistance rates of all anaerobic pathogens. Clinically, Bacteroides species have exhibited increasing resistance to many antibiotics, including cefoxitin, clindamycin, metronidazole, carbapenems, and fluoroquinolones (e.g., gatifloxacin, levofloxacin, and moxifloxacin).

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“…In E. faecalis, transport of lipoproteins across the membrane uses the Sec system, as no Tat mechanism is present and none of the 90 lipoproteins predicted in E. faecalis V583 harbours a Tat signal peptide (Reffuveille et al, 2011). Analysis in silico has revealed that prolipoprotein diacylglyceryl transferase (Lgt) and the signal peptidase II (Lsp) would be encoded by genes ef1748 and ef1723, respectively (Paulsen et al, 2003;Reffuveille et al, 2011). However, no description of the involvement of these genes in the processing of lipoproteins has been reported.…”

Section: Introductionmentioning

confidence: 99%

The prolipoprotein diacylglyceryl transferase (Lgt) of Enterococcus faecalis contributes to virulence

et al. 2012

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Enterococcus faecalis is an opportunistic pathogen responsible for nosocomial infections. Lipoproteins in Gram-positive bacteria are translocated across the plasma membrane and anchored by the fatty acid group. They perform critical roles, with some described as virulence determinants. The aim of this study was to explore the roles of E. faecalis lipoproteins in the stress response and virulence. We constructed a mutant affected in the predicted prolipoprotein diacylglyceryl transferase gene lgt, and examined the role of Lgt in membrane anchoring, growth, the stress response and virulence. Inactivation of lgt enhanced growth in a high concentration of Mn2+ or under oxidative stress in vitro, and significantly decreased virulence

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Role of Mobile DNA in the Evolution of Vancomycin-Resistant Enterococcus faecalis

Cited by 841 publications

References 17 publications

Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis

Regulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis

Bacteroides: the Good, the Bad, and the Nitty-Gritty

The prolipoprotein diacylglyceryl transferase (Lgt) of Enterococcus faecalis contributes to virulence

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