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. 1996 Apr;40(4):992–998. doi: 10.1128/aac.40.4.992

Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides.

L Wondrack 1, M Massa 1, B V Yang 1, J Sutcliffe 1
PMCID: PMC163245  PMID: 8849266

Abstract

Searching through a collection of 124 Staphylococcus aureus clinical strains, we found one isolate, strain 01A1032, that inactivates 14- and 16-membered macrolides. The products of inactivation were purified from supernatant fluids of cultures exposed to erythromycin for 3 h and were found to be identical to products of inactivation from Escherichia coli strains that encode either an EreA or EreB esterase. Further, strain 01A1032 was shown to be resistant to azithromycin, a 15-membered macrolide, by an alternate mechanism, efflux. Thus, strain 01A1032 harbors determinants encoding an esterase activity that hydrolyzes 14- and 16-membered macrolides and a macrolide efflux system.

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Selected References

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  1. Andremont A., Gerbaud G., Courvalin P. Plasmid-mediated high-level resistance to erythromycin in Escherichia coli. Antimicrob Agents Chemother. 1986 Mar;29(3):515–518. doi: 10.1128/aac.29.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arthur M., Andremont A., Courvalin P. Distribution of erythromycin esterase and rRNA methylase genes in members of the family Enterobacteriaceae highly resistant to erythromycin. Antimicrob Agents Chemother. 1987 Mar;31(3):404–409. doi: 10.1128/aac.31.3.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arthur M., Autissier D., Courvalin P. Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II. Nucleic Acids Res. 1986 Jun 25;14(12):4987–4999. doi: 10.1093/nar/14.12.4987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arthur M., Molinas C., Mabilat C., Courvalin P. Detection of erythromycin resistance by the polymerase chain reaction using primers in conserved regions of erm rRNA methylase genes. Antimicrob Agents Chemother. 1990 Oct;34(10):2024–2026. doi: 10.1128/aac.34.10.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barthélémy P., Autissier D., Gerbaud G., Courvalin P. Enzymic hydrolysis of erythromycin by a strain of Escherichia coli. A new mechanism of resistance. J Antibiot (Tokyo) 1984 Dec;37(12):1692–1696. doi: 10.7164/antibiotics.37.1692. [DOI] [PubMed] [Google Scholar]
  6. Bright G. M., Nagel A. A., Bordner J., Desai K. A., Dibrino J. N., Nowakowska J., Vincent L., Watrous R. M., Sciavolino F. C., English A. R. Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-AZA-9a-homoerythromycin A derivatives; a new class of macrolide antibiotics, the azalides. J Antibiot (Tokyo) 1988 Aug;41(8):1029–1047. doi: 10.7164/antibiotics.41.1029. [DOI] [PubMed] [Google Scholar]
  7. Brisson-Noël A., Delrieu P., Samain D., Courvalin P. Inactivation of lincosaminide antibiotics in Staphylococcus. Identification of lincosaminide O-nucleotidyltransferases and comparison of the corresponding resistance genes. J Biol Chem. 1988 Nov 5;263(31):15880–15887. [PubMed] [Google Scholar]
  8. Courvalin P. Transfer of antibiotic resistance genes between gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 1994 Jul;38(7):1447–1451. doi: 10.1128/aac.38.7.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Devriese L. A. Two new types of resistance to lincomycin in pathogenic staphylococci from animals. Ann Microbiol (Paris) 1980 Nov-Dec;131B(3):261–266. [PubMed] [Google Scholar]
  10. Dubnau D. Translational attenuation: the regulation of bacterial resistance to the macrolide-lincosamide-streptogramin B antibiotics. CRC Crit Rev Biochem. 1984;16(2):103–132. doi: 10.3109/10409238409102300. [DOI] [PubMed] [Google Scholar]
  11. Eady E. A., Ross J. I., Tipper J. L., Walters C. E., Cove J. H., Noble W. C. Distribution of genes encoding erythromycin ribosomal methylases and an erythromycin efflux pump in epidemiologically distinct groups of staphylococci. J Antimicrob Chemother. 1993 Feb;31(2):211–217. doi: 10.1093/jac/31.2.211. [DOI] [PubMed] [Google Scholar]
  12. Fernandez-Munoz R., Monro R. E., Torres-Pinedo R., Vazquez D. Substrate- and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol. lincomycin and erythromycin sites. Eur J Biochem. 1971 Nov 11;23(1):185–193. doi: 10.1111/j.1432-1033.1971.tb01607.x. [DOI] [PubMed] [Google Scholar]
  13. Ferre F. Quantitative or semi-quantitative PCR: reality versus myth. PCR Methods Appl. 1992 Aug;2(1):1–9. doi: 10.1101/gr.2.1.1. [DOI] [PubMed] [Google Scholar]
  14. Goffic F. L., Capmau M. L., Bonnet D., Cerceau C., Soussy C., Dublanchet A., Duval J. Plasmid-mediated pristinamycin resistance. PAC IIA: a new enzyme which modifies pristinamycin IIA. J Antibiot (Tokyo) 1977 Aug;30(8):665–669. doi: 10.7164/antibiotics.30.665. [DOI] [PubMed] [Google Scholar]
  15. Higgins C. F., Hyde S. C., Mimmack M. M., Gileadi U., Gill D. R., Gallagher M. P. Binding protein-dependent transport systems. J Bioenerg Biomembr. 1990 Aug;22(4):571–592. doi: 10.1007/BF00762962. [DOI] [PubMed] [Google Scholar]
  16. Jenkins G., Cundliffe E. Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics. Gene. 1991 Dec 1;108(1):55–62. doi: 10.1016/0378-1119(91)90487-v. [DOI] [PubMed] [Google Scholar]
  17. Jenssen W. D., Thakker-Varia S., Dubin D. T., Weinstein M. P. Prevalence of macrolides-lincosamides-streptogramin B resistance and erm gene classes among clinical strains of staphylococci and streptococci. Antimicrob Agents Chemother. 1987 Jun;31(6):883–888. doi: 10.1128/aac.31.6.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jánosi L., Nakajima Y., Hashimoto H. Characterization of plasmids that confer inducible resistance to 14-membered macrolides and streptogramin type B antibiotics in Staphylococcus aureus. Microbiol Immunol. 1990;34(9):723–735. doi: 10.1111/j.1348-0421.1990.tb01050.x. [DOI] [PubMed] [Google Scholar]
  19. Kono M., O'Hara K., Ebisu T. Purification and characterization of macrolide 2'-phosphotransferase type II from a strain of Escherichia coli highly resistant to macrolide antibiotics. FEMS Microbiol Lett. 1992 Oct 1;76(1-2):89–94. doi: 10.1016/0378-1097(92)90369-y. [DOI] [PubMed] [Google Scholar]
  20. Kuo M. S., Chirby D. G., Argoudelis A. D., Cialdella J. I., Coats J. H., Marshall V. P. Microbial glycosylation of erythromycin A. Antimicrob Agents Chemother. 1989 Dec;33(12):2089–2091. doi: 10.1128/aac.33.12.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kurath P., Jones P. H., Egan R. S., Perun T. J. Acid degradation of erythromycin A and erythromycin B. Experientia. 1971 Apr 15;27(4):362–362. doi: 10.1007/BF02137246. [DOI] [PubMed] [Google Scholar]
  22. Lai C. J., Weisblum B. Altered methylation of ribosomal RNA in an erythromycin-resistant strain of Staphylococcus aureus. Proc Natl Acad Sci U S A. 1971 Apr;68(4):856–860. doi: 10.1073/pnas.68.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lampson B. C., von David W., Parisi J. T. Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis. Antimicrob Agents Chemother. 1986 Nov;30(5):653–658. doi: 10.1128/aac.30.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Le Goffic F., Capmau M. L., Abbe J., Cerceau C., Dublanchet A., Duval J. Plasmid mediated pristinamycin resistance: PH 1A, a pristinamycin 1A hydrolase. Ann Microbiol (Paris) 1977 Nov-Dec;128B(4):471–474. [PubMed] [Google Scholar]
  25. Leclercq R., Brisson-Noël A., Duval J., Courvalin P. Phenotypic expression and genetic heterogeneity of lincosamide inactivation in Staphylococcus spp. Antimicrob Agents Chemother. 1987 Dec;31(12):1887–1891. doi: 10.1128/aac.31.12.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Leclercq R., Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother. 1991 Jul;35(7):1267–1272. doi: 10.1128/aac.35.7.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Leclercq R., Courvalin P. Intrinsic and unusual resistance to macrolide, lincosamide, and streptogramin antibiotics in bacteria. Antimicrob Agents Chemother. 1991 Jul;35(7):1273–1276. doi: 10.1128/aac.35.7.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mabilat C., Goussard S., Sougakoff W., Spencer R. C., Courvalin P. Direct sequencing of the amplified structural gene and promoter for the extended-broad-spectrum beta-lactamase TEM-9 (RHH-1) of Klebsiella pneumoniae. Plasmid. 1990 Jan;23(1):27–34. doi: 10.1016/0147-619x(90)90041-a. [DOI] [PubMed] [Google Scholar]
  29. Matsuoka M., Endou K., Saitoh S., Katoh M., Nakajima Y. A mechanism of resistance to partial macrolide and streptogramin B antibiotics in Staphylococcus aureus clinically isolated in Hungary. Biol Pharm Bull. 1995 Nov;18(11):1482–1486. doi: 10.1248/bpb.18.1482. [DOI] [PubMed] [Google Scholar]
  30. Matsuoka M., Jánosi L., Endou K., Saitoh S., Hashimoto H., Nakajima Y. An increase of 63 kDa-protein present in the cell membranes of Staphylococcus aureus that bears a plasmid mediating inducible resistance to partial macrolide and streptogramin B antibiotics. Biol Pharm Bull. 1993 Dec;16(12):1288–1290. doi: 10.1248/bpb.16.1288. [DOI] [PubMed] [Google Scholar]
  31. Milton I. D., Hewitt C. L., Harwood C. R. Cloning and sequencing of a plasmid-mediated erythromycin resistance determinant from Staphylococcus xylosus. FEMS Microbiol Lett. 1992 Oct 1;76(1-2):141–147. doi: 10.1016/0378-1097(92)90377-z. [DOI] [PubMed] [Google Scholar]
  32. Noguchi N., Emura A., Matsuyama H., O'Hara K., Sasatsu M., Kono M. Nucleotide sequence and characterization of erythromycin resistance determinant that encodes macrolide 2'-phosphotransferase I in Escherichia coli. Antimicrob Agents Chemother. 1995 Oct;39(10):2359–2363. doi: 10.1128/aac.39.10.2359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. O'Hara K. Application of nuclear magnetic resonance spectrometry to measure the activity of bacterial macrolide esterase. Microbios. 1994;79(321):231–239. [PubMed] [Google Scholar]
  34. O'Hara K., Kanda T., Ohmiya K., Ebisu T., Kono M. Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin. Antimicrob Agents Chemother. 1989 Aug;33(8):1354–1357. doi: 10.1128/aac.33.8.1354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ounissi H., Courvalin P. Nucleotide sequence of the gene ereA encoding the erythromycin esterase in Escherichia coli. Gene. 1985;35(3):271–278. doi: 10.1016/0378-1119(85)90005-8. [DOI] [PubMed] [Google Scholar]
  36. Ross J. I., Eady E. A., Cove J. H., Baumberg S. Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact. Gene. 1995 Feb 3;153(1):93–98. doi: 10.1016/0378-1119(94)00833-e. [DOI] [PubMed] [Google Scholar]
  37. Ross J. I., Eady E. A., Cove J. H., Cunliffe W. J., Baumberg S., Wootton J. C. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol. 1990 Jul;4(7):1207–1214. doi: 10.1111/j.1365-2958.1990.tb00696.x. [DOI] [PubMed] [Google Scholar]
  38. Ross J. I., Farrell A. M., Eady E. A., Cove J. H., Cunliffe W. J. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis. J Antimicrob Chemother. 1989 Dec;24(6):851–862. doi: 10.1093/jac/24.6.851. [DOI] [PubMed] [Google Scholar]
  39. Schoner B., Geistlich M., Rosteck P., Jr, Rao R. N., Seno E., Reynolds P., Cox K., Burgett S., Hershberger C. Sequence similarity between macrolide-resistance determinants and ATP-binding transport proteins. Gene. 1992 Jun 15;115(1-2):93–96. doi: 10.1016/0378-1119(92)90545-z. [DOI] [PubMed] [Google Scholar]
  40. Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother. 1995 Mar;39(3):577–585. doi: 10.1128/AAC.39.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weisblum B. Inducible resistance to macrolides, lincosamides and streptogramin type B antibiotics: the resistance phenotype, its biological diversity, and structural elements that regulate expression--a review. J Antimicrob Chemother. 1985 Jul;16 (Suppl A):63–90. doi: 10.1093/jac/16.suppl_a.63. [DOI] [PubMed] [Google Scholar]
  42. Weisblum B. Insights into erythromycin action from studies of its activity as inducer of resistance. Antimicrob Agents Chemother. 1995 Apr;39(4):797–805. doi: 10.1128/aac.39.4.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Westh H., Hougaard D. M., Vuust J., Rosdahl V. T. Prevalence of erm gene classes in erythromycin-resistant Staphylococcus aureus strains isolated between 1959 and 1988. Antimicrob Agents Chemother. 1995 Feb;39(2):369–373. doi: 10.1128/aac.39.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]

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