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J Bacteriol. Dec 1994; 176(23): 7335–7344.
PMCID: PMC197123

Genetic structure of the Enterococcus faecalis plasmid pAD1-encoded cytolytic toxin system and its relationship to lantibiotic determinants.

Abstract

Pheromone-responsive conjugative plasmids are unique to the species Enterococcus faecalis. Many pheromone-responsive plasmids, including those frequently isolated from sites of infection, express a novel cytolysin that possesses both hemolytic and bacteriocin activities. Further, this cytolysin has been shown to be a toxin in several disease models. In the present study, nucleotide sequence determination, mutagenesis, and complementation analysis were used to determine the organization of the E. faecalis plasmid pAD1 cytolysin determinant. Four open reading frames are required for expression of the cytolysin precursor (cylLL, cylLS, cylM, and cylB). The inferred products of two of these open reading frames, CyILL and CyILS, constitute the cytolysin precursor and bear structural resemblance to posttranslationally modified bacteriocins termed lantibiotics. Similarities between the organization of the E. faecalis cytolysin determinant and expression units for lantibiotics exist, indicating that the E. faecalis cytolysin represents a new branch of this class and is the first known to possess toxin activity.

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  • Banerjee S, Hansen JN. Structure and expression of a gene encoding the precursor of subtilin, a small protein antibiotic. J Biol Chem. 1988 Jul 5;263(19):9508–9514. [PubMed]
  • Benson SA, Hall MN, Silhavy TJ. Genetic analysis of protein export in Escherichia coli K12. Annu Rev Biochem. 1985;54:101–134. [PubMed]
  • Berry AM, Yother J, Briles DE, Hansman D, Paton JC. Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae. Infect Immun. 1989 Jul;57(7):2037–2042. [PMC free article] [PubMed]
  • BROCK TD, DAVIE JM. PROBABLE IDENTITY OF A GROUP D HEMOLYSIN WITH A BACTERIOCINE. J Bacteriol. 1963 Oct;86:708–712. [PMC free article] [PubMed]
  • BROCK TD, PEACHER B, PIERSON D. SURVEY OF THE BACTERIOCINES OF ENTEROCOCCI. J Bacteriol. 1963 Oct;86:702–707. [PMC free article] [PubMed]
  • Chow JW, Thal LA, Perri MB, Vazquez JA, Donabedian SM, Clewell DB, Zervos MJ. Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis. Antimicrob Agents Chemother. 1993 Nov;37(11):2474–2477. [PMC free article] [PubMed]
  • Chung YJ, Steen MT, Hansen JN. The subtilin gene of Bacillus subtilis ATCC 6633 is encoded in an operon that contains a homolog of the hemolysin B transport protein. J Bacteriol. 1992 Feb;174(4):1417–1422. [PMC free article] [PubMed]
  • Clewell DB. Bacterial sex pheromone-induced plasmid transfer. Cell. 1993 Apr 9;73(1):9–12. [PubMed]
  • Clewell DB, Tomich PK, Gawron-Burke MC, Franke AE, Yagi Y, An FY. Mapping of Streptococcus faecalis plasmids pAD1 and pAD2 and studies relating to transposition of Tn917. J Bacteriol. 1982 Dec;152(3):1220–1230. [PMC free article] [PubMed]
  • Cruz-Rodz AL, Gilmore MS. High efficiency introduction of plasmid DNA into glycine treated Enterococcus faecalis by electroporation. Mol Gen Genet. 1990 Oct;224(1):152–154. [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Dower WJ, Miller JF, Ragsdale CW. High efficiency transformation of E. coli by high voltage electroporation. Nucleic Acids Res. 1988 Jul 11;16(13):6127–6145. [PMC free article] [PubMed]
  • Fath MJ, Kolter R. ABC transporters: bacterial exporters. Microbiol Rev. 1993 Dec;57(4):995–1017. [PMC free article] [PubMed]
  • Gilmore MS, Segarra RA, Booth MC. An HlyB-type function is required for expression of the Enterococcus faecalis hemolysin/bacteriocin. Infect Immun. 1990 Dec;58(12):3914–3923. [PMC free article] [PubMed]
  • Granato PA, Jackson RW. Bicomponent nature of lysin from Streptococcus zymogenes. J Bacteriol. 1969 Nov;100(2):865–868. [PMC free article] [PubMed]
  • Hansen JN. Antibiotics synthesized by posttranslational modification. Annu Rev Microbiol. 1993;47:535–564. [PubMed]
  • Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. [PubMed]
  • Hershfield V. Plasmids mediating multiple drug resistance in group B streptococcus: transferability and molecular properties. Plasmid. 1979 Jan;2(1):137–149. [PubMed]
  • Huycke MM, Spiegel CA, Gilmore MS. Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. Antimicrob Agents Chemother. 1991 Aug;35(8):1626–1634. [PMC free article] [PubMed]
  • Ike Y, Clewell DB. Evidence that the hemolysin/bacteriocin phenotype of Enterococcus faecalis subsp. zymogenes can be determined by plasmids in different incompatibility groups as well as by the chromosome. J Bacteriol. 1992 Dec;174(24):8172–8177. [PMC free article] [PubMed]
  • Ike Y, Clewell DB, Segarra RA, Gilmore MS. Genetic analysis of the pAD1 hemolysin/bacteriocin determinant in Enterococcus faecalis: Tn917 insertional mutagenesis and cloning. J Bacteriol. 1990 Jan;172(1):155–163. [PMC free article] [PubMed]
  • Ike Y, Hashimoto H, Clewell DB. Hemolysin of Streptococcus faecalis subspecies zymogenes contributes to virulence in mice. Infect Immun. 1984 Aug;45(2):528–530. [PMC free article] [PubMed]
  • Ike Y, Hashimoto H, Clewell DB. High incidence of hemolysin production by Enterococcus (Streptococcus) faecalis strains associated with human parenteral infections. J Clin Microbiol. 1987 Aug;25(8):1524–1528. [PMC free article] [PubMed]
  • Jett BD, Gilmore MS. The growth-inhibitory effect of the Enterococcus faecalis bacteriocin encoded by pAD1 extends to the oral streptococci. J Dent Res. 1990 Oct;69(10):1640–1645. [PubMed]
  • Jett BD, Huycke MM, Gilmore MS. Virulence of enterococci. Clin Microbiol Rev. 1994 Oct;7(4):462–478. [PMC free article] [PubMed]
  • Jett BD, Jensen HG, Nordquist RE, Gilmore MS. Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmitis. Infect Immun. 1992 Jun;60(6):2445–2452. [PMC free article] [PubMed]
  • Kaletta C, Entian KD. Nisin, a peptide antibiotic: cloning and sequencing of the nisA gene and posttranslational processing of its peptide product. J Bacteriol. 1989 Mar;171(3):1597–1601. [PMC free article] [PubMed]
  • Kaletta C, Entian KD, Kellner R, Jung G, Reis M, Sahl HG. Pep5, a new lantibiotic: structural gene isolation and prepeptide sequence. Arch Microbiol. 1989;152(1):16–19. [PubMed]
  • Klein C, Kaletta C, Schnell N, Entian KD. Analysis of genes involved in biosynthesis of the lantibiotic subtilin. Appl Environ Microbiol. 1992 Jan;58(1):132–142. [PMC free article] [PubMed]
  • Kolter R, Moreno F. Genetics of ribosomally synthesized peptide antibiotics. Annu Rev Microbiol. 1992;46:141–163. [PubMed]
  • König W, Faltin Y, Scheffer J, Schöffler H, Braun V. Role of cell-bound hemolysin as a pathogenicity factor for Serratia infections. Infect Immun. 1987 Nov;55(11):2554–2561. [PMC free article] [PubMed]
  • Kuipers OP, Beerthuyzen MM, Siezen RJ, De Vos WM. Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis. Requirement of expression of the nisA and nisI genes for development of immunity. Eur J Biochem. 1993 Aug 15;216(1):281–291. [PubMed]
  • Schnell N, Engelke G, Augustin J, Rosenstein R, Ungermann V, Götz F, Entian KD. Analysis of genes involved in the biosynthesis of lantibiotic epidermin. Eur J Biochem. 1992 Feb 15;204(1):57–68. [PubMed]
  • Schnell N, Entian KD, Schneider U, Götz F, Zähner H, Kellner R, Jung G. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature. 1988 May 19;333(6170):276–278. [PubMed]
  • Segarra RA, Booth MC, Morales DA, Huycke MM, Gilmore MS. Molecular characterization of the Enterococcus faecalis cytolysin activator. Infect Immun. 1991 Apr;59(4):1239–1246. [PMC free article] [PubMed]
  • Shaw JH, Clewell DB. Complete nucleotide sequence of macrolide-lincosamide-streptogramin B-resistance transposon Tn917 in Streptococcus faecalis. J Bacteriol. 1985 Nov;164(2):782–796. [PMC free article] [PubMed]
  • Trieu-Cuot P, Carlier C, Poyart-Salmeron C, Courvalin P. A pair of mobilizable shuttle vectors conferring resistance to spectinomycin for molecular cloning in Escherichia coli and in gram-positive bacteria. Nucleic Acids Res. 1990 Jul 25;18(14):4296–4296. [PMC free article] [PubMed]
  • van der Meer JR, Polman J, Beerthuyzen MM, Siezen RJ, Kuipers OP, De Vos WM. Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. J Bacteriol. 1993 May;175(9):2578–2588. [PMC free article] [PubMed]
  • Welch RA, Dellinger EP, Minshew B, Falkow S. Haemolysin contributes to virulence of extra-intestinal E. coli infections. Nature. 1981 Dec 17;294(5842):665–667. [PubMed]
  • Welch RA, Falkow S. Characterization of Escherichia coli hemolysins conferring quantitative differences in virulence. Infect Immun. 1984 Jan;43(1):156–160. [PMC free article] [PubMed]
  • WILLIAMS NB, FORBES MA, BLAU E, EICKENBERG CF. A study of the simultaneous occurrence of Enterococci, Lactobacilli, and yeasts in saliva from human beings. J Dent Res. 1950 Oct;29(5):563–570. [PubMed]
  • Yagi Y, Clewell DB. Recombination-deficient mutant of Streptococcus faecalis. J Bacteriol. 1980 Aug;143(2):966–970. [PMC free article] [PubMed]

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