Inducible, transferable resistance to vancomycin in Enterococcus faecalis A256.
A strain of Enterococcus faecalis (A256) was isolated from the urine of a patient with urinary sepsis and was found to exhibit susceptibilities (micrograms per milliliter) to various glycopeptides as follows: vancomycin, 256; teicoplanin, 16; 62208, 512; 62211, 4; and 62476, 16. As judged by growth rates before and after exposure to sub-MICs of glycopeptides, vancomycin and 62476 induced self-resistance, 62208 and 62211 induced slight self-resistance, and teicoplanin did not induce self-resistance. Vancomycin induced cross-resistance to all other glycopeptides tested, as judged both in growth experiments and by direct measurement of inhibition of peptidoglycan synthesis in cells exposed to sub-MICs of vancomycin. Thus, the spectra of activity of the glycopeptides were not correlated with their patterns of induction. There was a correlation between the increased synthesis of a 39-kilodalton (kDa) protein located in the cytoplasmic membrane and the induction of resistance. Protoplasts of A256 were susceptible to inhibition of peptidoglycan synthesis by vancomycin at levels similar to those for susceptible strains. Vancomycin resistance was transferable on filters from the parent strain to E. faecalis JH2-2 at a frequency of about 10(-7), and the 39-kDa protein was also inducible by glycopeptides in these transconjugants. We conclude that A256 is resistant to glycopeptides by virtue of the synthesis of a 39-kDa cytoplasmic membrane protein, that this protein is probably involved in preventing access of the glycopeptides to their peptidoglycan targets, and that this resistance is transferable, probably by conjugation.
Shlaes
D M
DM
Département de Microbiologie Médicale, Faculté de Médecine, Université Pierre et Marie Curie, Paris, France.
Bouvet
A
A
Devine
C
C
Shlaes
J H
JH
al-Obeid
S
S
Williamson
R
R
D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000096:biosynthesis; D011523:Protoplasts / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate; D014552:Urinary Tract Infections / Q000382:microbiology; D014640:Vancomycin / Q000494:pharmacology*
D001425:Bacterial Outer Membrane Proteins; D006020:Glycopeptides; D010457:Peptidoglycan; D012967:Sodium Dodecyl Sulfate; D014640:Vancomycin