• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. Oct 1997; 41(10): 2251–2255.
PMCID: PMC164101

mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae.


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.

Full Text

The Full Text of this article is available as a PDF (164K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Appelbaum PC. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992 Jul;15(1):77–83. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Breiman RF, Butler JC, Tenover FC, Elliott JA, Facklam RR. Emergence of drug-resistant pneumococcal infections in the United States. JAMA. 1994 Jun 15;271(23):1831–1835. [PubMed]
  • Bright GM, Nagel AA, Bordner J, Desai KA, Dibrino JN, Nowakowska J, Vincent L, Watrous RM, Sciavolino FC, English AR, et al. 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. [PubMed]
  • Chang AC, Cohen SN. Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid. J Bacteriol. 1978 Jun;134(3):1141–1156. [PMC free article] [PubMed]
  • Clancy J, Petitpas J, Dib-Hajj F, Yuan W, Cronan M, Kamath AV, Bergeron J, Retsema JA. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol Microbiol. 1996 Dec;22(5):867–879. [PubMed]
  • Claverys JP, Dintilhac A, Pestova EV, Martin B, Morrison DA. 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. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Devine SE, Boeke JD. 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. [PMC free article] [PubMed]
  • Fasola EL, Bajaksouzian S, Appelbaum PC, Jacobs MR. Variation in erythromycin and clindamycin susceptibilities of Streptococcus pneumoniae by four test methods. Antimicrob Agents Chemother. 1997 Jan;41(1):129–134. [PMC free article] [PubMed]
  • Gómez J, Ruiz-Gómez J, Hernández-Cardona JL, Núez ML, 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. [PubMed]
  • Håvarstein LS, Coomaraswamy G, Morrison DA. 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. [PMC free article] [PubMed]
  • Leclercq R, Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother. 1991 Jul;35(7):1267–1272. [PMC free article] [PubMed]
  • Lewis K. Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem Sci. 1994 Mar;19(3):119–123. [PubMed]
  • McCracken GH., Jr Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics. Pediatr Infect Dis J. 1995 May;14(5):424–428. [PubMed]
  • Milton ID, Hewitt CL, Harwood CR. Cloning and sequencing of a plasmid-mediated erythromycin resistance determinant from Staphylococcus xylosus. FEMS Microbiol Lett. 1992 Oct 1;76(1-2):141–147. [PubMed]
  • Nelson CT, Mason EO, Jr, Kaplan SL. 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. [PubMed]
  • Nikaido H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994 Apr 15;264(5157):382–388. [PubMed]
  • Phillips G, Parratt D, Orange GV, Harper I, McEwan H, Young N. Erythromycin-resistant Streptococcus pyogenes. J Antimicrob Chemother. 1990 Apr;25(4):723–724. [PubMed]
  • Ross JI, Eady EA, Cove JH, 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. [PubMed]
  • Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S, Wootton JC. 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. [PubMed]
  • Ross JI, Farrell AM, Eady EA, Cove JH, Cunliffe WJ. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis. J Antimicrob Chemother. 1989 Dec;24(6):851–862. [PubMed]
  • Scott RJ, Naidoo J, Lightfoot NF, George RC. A community outbreak of group A beta haemolytic streptococci with transferable resistance to erythromycin. Epidemiol Infect. 1989 Feb;102(1):85–91. [PMC free article] [PubMed]
  • Seppälä H, Nissinen A, Järvinen H, Huovinen S, Henriksson T, Herva E, Holm SE, Jahkola M, Katila ML, Klaukka T, et al. Resistance to erythromycin in group A streptococci. N Engl J Med. 1992 Jan 30;326(5):292–297. [PubMed]
  • 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. [PubMed]
  • Shortridge VD, Flamm RK, Ramer N, Beyer J, Tanaka SK. Novel mechanism of macrolide resistance in Streptococcus pneumoniae. Diagn Microbiol Infect Dis. 1996 Oct;26(2):73–78. [PubMed]
  • Stingemore N, Francis GR, Toohey M, McGechie DB. The emergence of erythromycin resistance in Streptococcus pyogenes in Fremantle, Western Australia. Med J Aust. 1989 Jun 5;150(11):626–631. [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Welby PL, Keller DS, Cromien JL, Tebas P, Storch GA. 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. [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...