TY - JOUR
T1 - ksgA mutations confer resistance to kasugamycin in Neisseria gonorrhoeae
AU - Duffin, Paul M.
AU - Seifert, H. Steven
N1 - Funding Information:
Funding : This work was supported by National Institutes of Health (NIH) grants R01 AI055977, R01 AI044239 and R37 AI033493 from the US National Institutes of Health to HSS.
PY - 2009/4
Y1 - 2009/4
N2 - The aminoglycoside antibiotic kasugamycin (KSG) inhibits translation initiation and thus the growth of many bacteria. In this study, we tested the susceptibilities to KSG of 22 low-passage clinical isolates and 2 laboratory strains of Neisseria gonorrhoeae. Although the range of KSG minimum inhibitory concentrations (MICs) was narrow (seven-fold), clinical isolates and laboratory strains fell into three distinct classes of KSG sensitivity, susceptible, somewhat sensitive and resistant, with MICs of 30, 60-100 and 200 μg/mL, respectively. Two genes have previously been shown to be involved in bacterial KSG resistance: rpsI, which encodes the 30S ribosomal subunit S9 protein; and ksgA, which encodes a predicted dimethyltransferase. Although sequencing of rpsI and ksgA from clinical isolates revealed polymorphisms, none correlated with the MICs of KSG. Ten spontaneous KSG-resistant (KSGR) mutants were isolated from laboratory strain FA1090 at a frequency of <4.4 × 10-6 resistant colony-forming units (CFU)/total CFU. All isolated KSGR variants had mutations in ksgA, whilst no mutations were observed in rpsI. ksgA mutations conferring KSG resistance included four point mutations, two in-frame and one out-of-frame deletions, one in-frame duplication and two frame-shift insertions. These data show a narrow range of susceptibilities for the clinical isolates and laboratory strains examined; moreover, the differences in MICs do not correlate with nucleotide polymorphisms in rpsI or ksgA. Additionally, spontaneous KSGR mutants arise by a variety of ksgA mutations.
AB - The aminoglycoside antibiotic kasugamycin (KSG) inhibits translation initiation and thus the growth of many bacteria. In this study, we tested the susceptibilities to KSG of 22 low-passage clinical isolates and 2 laboratory strains of Neisseria gonorrhoeae. Although the range of KSG minimum inhibitory concentrations (MICs) was narrow (seven-fold), clinical isolates and laboratory strains fell into three distinct classes of KSG sensitivity, susceptible, somewhat sensitive and resistant, with MICs of 30, 60-100 and 200 μg/mL, respectively. Two genes have previously been shown to be involved in bacterial KSG resistance: rpsI, which encodes the 30S ribosomal subunit S9 protein; and ksgA, which encodes a predicted dimethyltransferase. Although sequencing of rpsI and ksgA from clinical isolates revealed polymorphisms, none correlated with the MICs of KSG. Ten spontaneous KSG-resistant (KSGR) mutants were isolated from laboratory strain FA1090 at a frequency of <4.4 × 10-6 resistant colony-forming units (CFU)/total CFU. All isolated KSGR variants had mutations in ksgA, whilst no mutations were observed in rpsI. ksgA mutations conferring KSG resistance included four point mutations, two in-frame and one out-of-frame deletions, one in-frame duplication and two frame-shift insertions. These data show a narrow range of susceptibilities for the clinical isolates and laboratory strains examined; moreover, the differences in MICs do not correlate with nucleotide polymorphisms in rpsI or ksgA. Additionally, spontaneous KSGR mutants arise by a variety of ksgA mutations.
KW - Antibiotic resistance
KW - Gonorrhoea
KW - Mutagenesis
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U2 - 10.1016/j.ijantimicag.2008.08.030
DO - 10.1016/j.ijantimicag.2008.08.030
M3 - Article
C2 - 19097863
AN - SCOPUS:61449235258
SN - 0924-8579
VL - 33
SP - 321
EP - 327
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 4
ER -