Affiliation:
1. Departments of Medicine
2. Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
3. VA Medical Center, Decatur, Georgia 30033
Abstract
ABSTRACT
Macrolide resistance in
Streptococcus pneumoniae
due to efflux has emerged as an important worldwide clinical problem over the past decade. Efflux is mediated by the genes of the genetic element mega (
m
acrolide
e
fflux
g
enetic
a
ssembly) and related elements, such as Tn
1207.1
. These elements contain two adjacent genes,
mef
(
mefE
or
mefA
) and the closely related
mel
gene (
msrA
homolog), encoding a proton motive force pump and a putative ATP-binding cassette transporter homolog, and are transcribed as an operon (M. Del Grosso et al., J. Clin. Microbiol.
40:
774-778, 2004; K. Gay and D. S. Stephens, J. Infect. Dis.
184:
56-65, 2001; and M. Santagati et al., Antimicrob. Agents Chemother.
44:
2585-2587, 2000). Previous studies have shown that Mef is required for macrolide resistance in
S. pneumoniae
; however, the contribution of Mel has not been fully determined. Independent deletions were constructed in
mefE
and
mel
in the serotype 14 macrolide-resistant strains GA16638 (erythromycin [Em] MIC, 8 to 16 μg/ml) and GA17719 (Em MIC, 2 to 4 μg/ml), which contain allelic variations in the mega element. The MICs to erythromycin were significantly reduced for the independent deletion mutants of both
mefE
and
mel
compared to those of the parent strains and further reduced threefold to fourfold to Em MICs of <0.15 μg/ml with
mefE mel
double mutants. Using quantitative reverse transcription-PCR, the expression of
mefE
in the
mel
deletion mutants was increased more than 10-fold. However, in the
mefE
deletion mutants, the expression of
mel
did not differ significantly from the parent strains. The expression of both
mefE
and
mel
was inducible by erythromycin. These data indicate a requirement for both Mef and Mel in the novel efflux-mediated macrolide resistance system in
S. pneumoniae
and other gram-positive bacteria and that the system is inducible by macrolides.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
95 articles.
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