Abstract
Recently, it was shown that a significant number of erythromycin-resistant Streptococcus pneumoniae and Streptococcus pyogenes strains contain a determinant that mediates resistance via a putative efflux pump. The gene encoding the erythromycin-resistant determinant was cloned and sequenced from three strains of S. pneumoniae bearing the M phenotype (macrolide resistant but clindamycin and streptogramin B susceptible). The DNA sequences of mefE were nearly identical, with only 2-nucleotide differences between genes from any two strains. When the mefE sequences were compared to the mefA sequence from S. pyogenes, the two genes were found to be closely related (90% identity). Strains of S. pneumoniae were constructed to confirm that mefE is necessary to confer erythromycin resistance and to explore the substrate specificity of the pump; no substrates other than 14- and 15-membered macrolides were identified.
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- Appelbaum P. C. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992 Jul;15(1):77–83. doi: 10.1093/clinids/15.1.77. [DOI] [PubMed] [Google Scholar]
- 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]
- Breiman R. F., Butler J. C., Tenover F. C., Elliott J. A., Facklam R. R. Emergence of drug-resistant pneumococcal infections in the United States. JAMA. 1994 Jun 15;271(23):1831–1835. [PubMed] [Google Scholar]
- 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]
- Chang A. C., Cohen S. N. Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid. J Bacteriol. 1978 Jun;134(3):1141–1156. doi: 10.1128/jb.134.3.1141-1156.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clancy J., Petitpas J., Dib-Hajj F., Yuan W., Cronan M., Kamath A. V., Bergeron J., Retsema J. A. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol Microbiol. 1996 Dec;22(5):867–879. doi: 10.1046/j.1365-2958.1996.01521.x. [DOI] [PubMed] [Google Scholar]
- Claverys J. P., Dintilhac A., Pestova E. V., Martin B., Morrison D. A. Construction and evaluation of new drug-resistance cassettes for gene disruption mutagenesis in Streptococcus pneumoniae, using an ami test platform. Gene. 1995 Oct 16;164(1):123–128. doi: 10.1016/0378-1119(95)00485-o. [DOI] [PubMed] [Google Scholar]
- Cornaglia G., Ligozzi M., Mazzariol A., Valentini M., Orefici G., Fontana R. Rapid increase of resistance to erythromycin and clindamycin in Streptococcus pyogenes in Italy, 1993-1995. The Italian Surveillance Group for Antimicrobial Resistance. Emerg Infect Dis. 1996 Oct-Dec;2(4):339–342. doi: 10.3201/eid0204.960410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devine S. E., Boeke J. D. Efficient integration of artificial transposons into plasmid targets in vitro: a useful tool for DNA mapping, sequencing and genetic analysis. Nucleic Acids Res. 1994 Sep 11;22(18):3765–3772. doi: 10.1093/nar/22.18.3765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fasola E. L., Bajaksouzian S., Appelbaum P. C., Jacobs M. R. Variation in erythromycin and clindamycin susceptibilities of Streptococcus pneumoniae by four test methods. Antimicrob Agents Chemother. 1997 Jan;41(1):129–134. doi: 10.1128/aac.41.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gómez J., Ruiz-Gómez J., Hernández-Cardona J. L., Núez M. L., Canteras M., Valdés M. Antibiotic resistance patterns of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: a prospective study in Murcia, Spain, 1983-1992. Chemotherapy. 1994 Sep-Oct;40(5):299–303. doi: 10.1159/000239210. [DOI] [PubMed] [Google Scholar]
- Håvarstein L. S., Coomaraswamy G., Morrison D. A. An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11140–11144. doi: 10.1073/pnas.92.24.11140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lewis K. Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem Sci. 1994 Mar;19(3):119–123. doi: 10.1016/0968-0004(94)90204-6. [DOI] [PubMed] [Google Scholar]
- McCracken G. H., Jr Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. Pediatr Infect Dis J. 1995 May;14(5):424–428. doi: 10.1097/00006454-199505001-00004. [DOI] [PubMed] [Google Scholar]
- 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]
- Nelson C. T., Mason E. O., Jr, Kaplan S. L. Activity of oral antibiotics in middle ear and sinus infections caused by penicillin-resistant Streptococcus pneumoniae: implications for treatment. Pediatr Infect Dis J. 1994 Jul;13(7):585–589. doi: 10.1097/00006454-199407000-00001. [DOI] [PubMed] [Google Scholar]
- Nikaido H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994 Apr 15;264(5157):382–388. doi: 10.1126/science.8153625. [DOI] [PubMed] [Google Scholar]
- Phillips G., Parratt D., Orange G. V., Harper I., McEwan H., Young N. Erythromycin-resistant Streptococcus pyogenes. J Antimicrob Chemother. 1990 Apr;25(4):723–724. doi: 10.1093/jac/25.4.723. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Scott R. J., Naidoo J., Lightfoot N. F., George R. C. A community outbreak of group A beta haemolytic streptococci with transferable resistance to erythromycin. Epidemiol Infect. 1989 Feb;102(1):85–91. doi: 10.1017/s095026880002971x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seppälä H., Nissinen A., Järvinen H., Huovinen S., Henriksson T., Herva E., Holm S. E., Jahkola M., Katila M. L., Klaukka T. Resistance to erythromycin in group A streptococci. N Engl J Med. 1992 Jan 30;326(5):292–297. doi: 10.1056/NEJM199201303260503. [DOI] [PubMed] [Google Scholar]
- Seppälä H., Nissinen A., Yu Q., Huovinen P. Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland. J Antimicrob Chemother. 1993 Dec;32(6):885–891. doi: 10.1093/jac/32.6.885. [DOI] [PubMed] [Google Scholar]
- Shortridge V. D., Flamm R. K., Ramer N., Beyer J., Tanaka S. K. Novel mechanism of macrolide resistance in Streptococcus pneumoniae. Diagn Microbiol Infect Dis. 1996 Oct;26(2):73–78. doi: 10.1016/s0732-8893(96)00183-6. [DOI] [PubMed] [Google Scholar]
- Stingemore N., Francis G. R., Toohey M., McGechie D. B. The emergence of erythromycin resistance in Streptococcus pyogenes in Fremantle, Western Australia. Med J Aust. 1989 Jun 5;150(11):626-7, 630-1. doi: 10.5694/j.1326-5377.1989.tb136725.x. [DOI] [PubMed] [Google Scholar]
- Sutcliffe J., Grebe T., Tait-Kamradt A., Wondrack L. Detection of erythromycin-resistant determinants by PCR. Antimicrob Agents Chemother. 1996 Nov;40(11):2562–2566. doi: 10.1128/aac.40.11.2562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutcliffe J., Tait-Kamradt A., Wondrack L. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother. 1996 Aug;40(8):1817–1824. doi: 10.1128/aac.40.8.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trieu-Cuot P., Poyart-Salmeron C., Carlier C., Courvalin P. Nucleotide sequence of the erythromycin resistance gene of the conjugative transposon Tn1545. Nucleic Acids Res. 1990 Jun 25;18(12):3660–3660. doi: 10.1093/nar/18.12.3660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welby P. L., Keller D. S., Cromien J. L., Tebas P., Storch G. A. Resistance to penicillin and non-beta-lactam antibiotics of Streptococcus pneumoniae at a children's hospital. Pediatr Infect Dis J. 1994 Apr;13(4):281–287. doi: 10.1097/00006454-199404000-00007. [DOI] [PubMed] [Google Scholar]