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. 1995 Apr;39(4):830–833. doi: 10.1128/aac.39.4.830

Inducible and constitutive expression of resistance to glycopeptides and vancomycin dependence in glycopeptide-resistant Enterococcus avium.

A Rosato 1, J Pierre 1, D Billot-Klein 1, A Buu-Hoi 1, L Gutmann 1
PMCID: PMC162637  PMID: 7785979

Abstract

A clinical isolate of Enterococcus avium, Ea1, which exhibited inducible, low-level resistance to vancomycin and teicoplanin, and two mutants selected from this strain, Ea3 and Ea31, were studied. Ea3 was vancomycin dependent and derived from Ea1, while Ea31 was not vancomycin dependent, was constitutively resistant, and was derived from Ea3. Hybridization studies revealed that vanA was present in Ea1 and suggested that it was located on a high-molecular-weight plasmid. In the absence of induction, Ea1 synthesized only the natural UDP-MurNAc-pentapeptide precursor, and after induction it synthesized an additional precursor identified as UDP-MurNAc-tetrapeptide-D-lactate. The latter was the only precursor found in Ea3 and Ea31, even after precursor accumulation. From these results, we infer that (i) the low level of resistance to glycopeptides in strain Ea1 may be in part due to the residual synthesis of the normal precursor and (ii) the vancomycin dependence of mutant Ea3 could be due to the fact that this strain does not produce any peptidoglycan precursor in the absence of induction.

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Selected References

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  1. Adam M., Damblon C., Plaitin B., Christiaens L., Frère J. M. Chromogenic depsipeptide substrates for beta-lactamases and penicillin-sensitive DD-peptidases. Biochem J. 1990 Sep 1;270(2):525–529. doi: 10.1042/bj2700525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen N. E., Hobbs J. N., Jr, Richardson J. M., Riggin R. M. Biosynthesis of modified peptidoglycan precursors by vancomycin-resistant Enterococcus faecium. FEMS Microbiol Lett. 1992 Nov 1;77(1-3):109–115. doi: 10.1016/0378-1097(92)90140-j. [DOI] [PubMed] [Google Scholar]
  3. Arthur M., Courvalin P. Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1563–1571. doi: 10.1128/aac.37.8.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arthur M., Molinas C., Depardieu F., Courvalin P. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol. 1993 Jan;175(1):117–127. doi: 10.1128/jb.175.1.117-127.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Billot-Klein D., Gutmann L., Collatz E., van Heijenoort J. Analysis of peptidoglycan precursors in vancomycin-resistant enterococci. Antimicrob Agents Chemother. 1992 Jul;36(7):1487–1490. doi: 10.1128/aac.36.7.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Billot-Klein D., Gutmann L., Sablé S., Guittet E., van Heijenoort J. Modification of peptidoglycan precursors is a common feature of the low-level vancomycin-resistant VANB-type Enterococcus D366 and of the naturally glycopeptide-resistant species Lactobacillus casei, Pediococcus pentosaceus, Leuconostoc mesenteroides, and Enterococcus gallinarum. J Bacteriol. 1994 Apr;176(8):2398–2405. doi: 10.1128/jb.176.8.2398-2405.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bochner B. R., Ames B. N. Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography. J Biol Chem. 1982 Aug 25;257(16):9759–9769. [PubMed] [Google Scholar]
  8. Dutka-Malen S., Molinas C., Arthur M., Courvalin P. The VANA glycopeptide resistance protein is related to D-alanyl-D-alanine ligase cell wall biosynthesis enzymes. Mol Gen Genet. 1990 Dec;224(3):364–372. doi: 10.1007/BF00262430. [DOI] [PubMed] [Google Scholar]
  9. Flouret B., Mengin-Lecreulx D., van Heijenoort J. Reverse-phase high-pressure liquid chromatography of uridine diphosphate N-acetylmuramyl peptide precursors of bacterial cell wall peptidoglycan. Anal Biochem. 1981 Jun;114(1):59–63. doi: 10.1016/0003-2697(81)90451-6. [DOI] [PubMed] [Google Scholar]
  10. Fraimow H. S., Jungkind D. L., Lander D. W., Delso D. R., Dean J. L. Urinary tract infection with an Enterococcus faecalis isolate that requires vancomycin for growth. Ann Intern Med. 1994 Jul 1;121(1):22–26. doi: 10.7326/0003-4819-121-1-199407010-00004. [DOI] [PubMed] [Google Scholar]
  11. Gold H. S., Unal S., Cercenado E., Thauvin-Eliopoulos C., Eliopoulos G. M., Wennersten C. B., Moellering R. C., Jr A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1604–1609. doi: 10.1128/aac.37.8.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gutmann L., Billot-Klein D., al-Obeid S., Klare I., Francoual S., Collatz E., van Heijenoort J. Inducible carboxypeptidase activity in vancomycin-resistant enterococci. Antimicrob Agents Chemother. 1992 Jan;36(1):77–80. doi: 10.1128/aac.36.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gutmann L., al-Obeid S., Billot-Klein D., Guerrier M. L., Collatz E. Synergy and resistance to synergy between beta-lactam antibiotics and glycopeptides against glycopeptide-resistant strains of Enterococcus faecium. Antimicrob Agents Chemother. 1994 Apr;38(4):824–829. doi: 10.1128/aac.38.4.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Handwerger S., Pucci M. J., Volk K. J., Liu J., Lee M. S. The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate. J Bacteriol. 1992 Sep;174(18):5982–5984. doi: 10.1128/jb.174.18.5982-5984.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Le Bouguénec C., de Cespédès G., Horaud T. Molecular analysis of a composite chromosomal conjugative element (Tn3701) of Streptococcus pyogenes. J Bacteriol. 1988 Sep;170(9):3930–3936. doi: 10.1128/jb.170.9.3930-3936.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leclercq R., Derlot E., Weber M., Duval J., Courvalin P. Transferable vancomycin and teicoplanin resistance in Enterococcus faecium. Antimicrob Agents Chemother. 1989 Jan;33(1):10–15. doi: 10.1128/aac.33.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Messer J., Reynolds P. E. Modified peptidoglycan precursors produced by glycopeptide-resistant enterococci. FEMS Microbiol Lett. 1992 Jul 1;73(1-2):195–200. doi: 10.1016/0378-1097(92)90608-q. [DOI] [PubMed] [Google Scholar]
  18. Nicas T. I., Wu C. Y., Hobbs J. N., Jr, Preston D. A., Allen N. E. Characterization of vancomycin resistance in Enterococcus faecium and Enterococcus faecalis. Antimicrob Agents Chemother. 1989 Jul;33(7):1121–1124. doi: 10.1128/aac.33.7.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reynolds P. E., Depardieu F., Dutka-Malen S., Arthur M., Courvalin P. Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine. Mol Microbiol. 1994 Sep;13(6):1065–1070. doi: 10.1111/j.1365-2958.1994.tb00497.x. [DOI] [PubMed] [Google Scholar]
  20. Shlaes D. M., Bouvet A., Devine C., Shlaes J. H., al-Obeid S., Williamson R. Inducible, transferable resistance to vancomycin in Enterococcus faecalis A256. Antimicrob Agents Chemother. 1989 Feb;33(2):198–203. doi: 10.1128/aac.33.2.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Uttley A. H., Collins C. H., Naidoo J., George R. C. Vancomycin-resistant enterococci. Lancet. 1988 Jan 2;1(8575-6):57–58. doi: 10.1016/s0140-6736(88)91037-9. [DOI] [PubMed] [Google Scholar]
  22. Williamson R., Gutmann L., Horaud T., Delbos F., Acar J. F. Use of penicillin-binding proteins for the identification of enterococci. J Gen Microbiol. 1986 Jul;132(7):1929–1937. doi: 10.1099/00221287-132-7-1929. [DOI] [PubMed] [Google Scholar]
  23. al-Obeid S., Billot-Klein D., van Heijenoort J., Collatz E., Gutmann L. Replacement of the essential penicillin-binding protein 5 by high-molecular mass PBPs may explain vancomycin-beta-lactam synergy in low-level vancomycin-resistant Enterococcus faecium D366. FEMS Microbiol Lett. 1992 Feb 1;70(1):79–84. doi: 10.1016/0378-1097(92)90566-7. [DOI] [PubMed] [Google Scholar]
  24. al-Obeid S., Collatz E., Gutmann L. Mechanism of resistance to vancomycin in Enterococcus faecium D366 and Enterococcus faecalis A256. Antimicrob Agents Chemother. 1990 Feb;34(2):252–256. doi: 10.1128/aac.34.2.252. [DOI] [PMC free article] [PubMed] [Google Scholar]

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