Affiliation:
1. Departments of Medical Microbiology & Immunology1 and
2. Biological Sciences,2 University of Alberta, Edmonton, Alberta T6G 2H7, Canada
Abstract
ABSTRACT
The effects of mutations in host genes on tetracycline resistance mediated by the Tet(O) and Tet(M) ribosomal protection proteins, which originated in
Campylobacter
spp. and
Streptococcus
spp., respectively, were investigated by using mutants of
Salmonella typhimurium
and
Escherichia coli
. The
miaA
,
miaB
, and
miaAB
double mutants of
S. typhimurium
specify enzymes for tRNA modification at the adenosine at position 37, adjacent to the anticodon in tRNA. In
S. typhimurium
, this involves biosynthesis of
N
6
-(4-hydroxyisopentenyl)-2-methylthioadenosine (ms
2
io
6
A). The
miaA
mutation reduced the level of tetracycline resistance mediated by both Tet(O) and Tet(M), but the latter showed a greater effect, which was ascribed to the isopentenyl (i
6
) group or to a combination of the methylthioadenosine (ms
2
) and i
6
groups but not to the ms
2
group alone (specified by
miaB
). In addition, mutations in
E. coli rpsL
genes, generating both streptomycin-resistant and streptomycin-dependent strains, were also shown to reduce the level of tetracycline resistance mediated by Tet(O) and Tet(M). The single-site amino acid substitutions present in the
rpsL
mutations were pleiotropic in their effects on tetracycline MICs. These mutants affect translational accuracy and kinetics and suggest that Tet(O) and Tet(M) binding to the ribosome may be reduced or slowed in the
E. coli rpsL
mutants in which the S12 protein is altered. Data from both the
miaA
and
rpsL
mutant studies indicate a possible link between stability of the aminoacyl-tRNA in the ribosomal acceptor site and tetracycline resistance mediated by the ribosomal protection proteins.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
17 articles.
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