ef1097 and ypkK encode enterococcin V583 and corynicin JK, members of a new family of antimicrobial proteins (bacteriocins) with modular structure from Gram-positive bacteria

Swe, Pearl M.; Heng, Nicholas C. K.; Ting, Yi Tian; Baird, Hayley; Carne, Alan; Tauch, Andreas; Tagg, John; Jack, Ralph W.

doi:10.1099/mic.0.2007/010777-0

Cited by 19 publications

(30 citation statements)

References 44 publications

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“…The Fsr system regulates multiple virulence-related traits, including the secreted proteases GelE and SprE and a bacteriocin produced from the ef1097 gene (24)(25)(26). ef1097 encodes a 170-aa prepeptide, and cleavage of the secretion leader sequences results in the export of a 136-residue propeptide (EntV 136 ) that has bactericidal activity against Gram-positive bacteria and has been referred to as enterococcin V583 and enterocin O16 (25,27). The ef1097 gene is present in all E. faecalis strains sequenced to date (25), and we propose to name the gene product EntV, for Enterocin originally found in V583.…”

Section: Resultsmentioning

confidence: 99%

Enterococcus faecalisbacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence ofCandida albicans

Graham¹,

Cruz²,

Garsin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

189

184

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Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species also are among the most important and problematic, opportunistic nosocomial pathogens. Surprisingly, these two species antagonize each other's virulence in both nematode infection and in vitro biofilm models. We report here the identification of the E. faecalis bacteriocin, EntV, produced from the entV (ef1097) locus, as both necessary and sufficient for the reduction of C. albicans virulence and biofilm formation through the inhibition of hyphal formation, a critical virulence trait. A synthetic version of the mature 68-aa peptide potently blocks biofilm development on solid substrates in multiple media conditions and disrupts preformed biofilms, which are resistant to current antifungal agents. EntV 68 is protective in three fungal infection models at nanomolar or lower concentrations. First, nematodes treated with the peptide at 0.1 nM are completely resistant to killing by C. albicans. The peptide also protects macrophages and augments their antifungal activity. Finally, EntV 68 reduces epithelial invasion, inflammation, and fungal burden in a murine model of oropharyngeal candidiasis. In all three models, the peptide greatly reduces the number of fungal cells present in the hyphal form. Despite these profound effects, EntV 68 has no effect on C. albicans viability, even in the presence of significant host-mimicking stresses. These findings demonstrate that EntV has potential as an antifungal agent that targets virulence rather than viability.Candida albicans | Enterococcus faecalis | biofilms | bacteriocins

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Section: Resultsmentioning

confidence: 99%

Enterococcus faecalisbacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence ofCandida albicans

Graham¹,

Cruz²,

Garsin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

189

184

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“…EF_1097 is member of a family of antimicrobial proteins (10), and it has been demonstrated that the 12.8 kDa corresponding to EF_1097 residues 130 to 170 displays potent antimicrobial activity against E. faecalis (26). On the basis of our finding that GelE processed the enterocin O16 proprotein, we reasoned that in the V583⌬gelE strain, the native secreted EF_1097 proprotein should be intact.…”

Section: Resultsmentioning

confidence: 98%

“…To test this hypothesis, we assessed whether V583 with fsrB mutated (i.e., E. faecalis that tolerance to enterocin O16 is not related to the fsr regulatory system. It has previously been reported that a collection of E. faecalis strains were highly sensitive to a 12-kDa EF_1097-derived protein (136 amino acid residues) obtained by heterologous expression in E. coli (26). We therefore tested the sensitivity of 22 E. faecalis strains whose genomes have been sequenced to enterocin O16 but saw no growth inhibition (Table 4).…”

Section: Resultsmentioning

confidence: 99%

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ThefsrQuorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

et al. 2015

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A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. IMPORTANCEThe fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelEsprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons constitutes the elements necessary for the production of a bacteriocin-type peptide and that antimicrobial antagonism is an intrinsic function of fsr. The bacteriocin enterocin O16 consists of the 68 most C-terminal residues of the EF_1097 secreted proprotein. The GelE protease processes the EF_1097 proprotein into enterocin O16. In this manner, fsr signaling enables E. faecalis populations to express antimicrobial activity in a cell density-dependent manner. E nterococci are among the most common commensal lactic acid bacteria (LAB) in the gastrointestinal (GI) tracts of humans and animals. Throughout our lives, we receive frequent supplies of enterococci, especially from fermented foods (dairy, meat, and vegetable based). While some enterococci seem to establish themselves as part of the GI microbiota, most enterococcal strains only transiently inhabit the GI system. Enterococci are also prominent etiological agents of nosocomial infections (1). The increasing incidence of multiple-antibiotic-resistant nosocomial isolates makes the treatment of infection...

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“…Several protein bacteriocins from Gram-positive species are in fact cell-wall hydrolyzing (murolytic) enzymes, such as lysostaphin (24). Others, with largely unknown mechanisms, include the 37-kDa helveticin J (25), the 17-kDa streptococcin A-M57 (26), the 21.5-kDa dysgalacticin (27), and the similar 17-kDa proteins SA-M57, enterococcin V583, and corynicin JK (28). The three latter proteins have been studied in some detail, and it has been shown that the basic C-terminal regions of these otherwise acidic proteins are responsible for their killing activity.…”

Section: Discussionmentioning

confidence: 99%

New Type of Antimicrobial Protein Produced by the Plant Pathogen Clavibacter michiganensis subsp. michiganensis

Liu

Holtsmark

et al. 2013

Appl Environ Microbiol

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It has previously been shown that the tomato pathogen Clavibacter michiganensis subsp. michiganensis secretes a 14-kDa protein, C. michiganensis subsp. michiganensis AMP-I (CmmAMP-I), that inhibits growth of Clavibacter michiganensis subsp. sepedonicus, the causal agent of bacterial ring rot of potato. Using sequences obtained from tryptic fragments, we have identified the gene encoding CmmAMP-I and we have recombinantly produced the protein with an N-terminal intein tag. The gene sequence showed that CmmAMP-I contains a typical N-terminal signal peptide for Sec-dependent secretion. The recombinant protein was highly active, with 50% growth inhibition (IC 50 ) of approximately 10 pmol, but was not toxic to potato leaves or tubers. CmmAMP-I does not resemble any known protein and thus represents a completely new type of bacteriocin. Due to its high antimicrobial activity and its very narrow inhibitory spectrum, CmmAMP-1 may be of interest in combating potato ring rot disease.

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ef1097 and ypkK encode enterococcin V583 and corynicin JK, members of a new family of antimicrobial proteins (bacteriocins) with modular structure from Gram-positive bacteria

Cited by 19 publications

References 44 publications

Enterococcus faecalisbacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence ofCandida albicans

Enterococcus faecalisbacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence ofCandida albicans

ThefsrQuorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

New Type of Antimicrobial Protein Produced by the Plant Pathogen Clavibacter michiganensis subsp. michiganensis

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