Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype.
A Neisseria gonorrhoeae strain with a reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) = 0.5 microg/mL) was isolated among 398 clinical isolates obtained from 2000-2001 in Fukuoka City, Japan. The N. gonorrhoeae strain was negative for penicillinase production but it showed multidrug resistance against penicillin (MIC = 8 microg/mL), tetracycline (MIC = 4 microg/mL), azithromycin (MIC = 0.5 microg/mL) and ciprofloxacin (MIC = 16 microg/mL). The molecular mechanisms of the multidrug-resistant phenotype in this strain were analysed. Polymerase chain reaction and direct DNA sequencing were performed to identify mutations within the penA, ponA, mtrR, penB, gyrA and parC genes of the gonococcal strain, which thus explain the multidrug-resistant phenotype. The N. gonorrhoeae strain contained a significantly different sequence of the penA gene from that of the ceftriaxone-susceptible strains. Some regions of the transpeptidase domain within this penA gene were closely similar to those found in other Neisseria species such as Neisseria subflava, Neisseria flavescens or Neisseria perflava/sicca. This strain also included a ponA mutation that is associated with high-level resistance to penicillin, mtrR mutations that mediate overexpression of the MtrCDE efflux pump responsible for resistance to hydrophobic agents such as azithromycin, and penB mutations that reduce porin permeability to hydrophilic agents such as tetracycline. Moreover, this strain contained gyrA and parC mutations that confer high-level resistance to ciprofloxacin. These results indicate the emergence of a N. gonorrhoeae strain with reduced susceptibility to ceftriaxone, which also showed a multidrug-resistant phenotype that can be explained by the presence of multiple loci mutations associated with antibiotic resistance.
Tanaka
Masatoshi
M
Department of Urology, School of Medicine, Fukuoka University, Jonan-ku, Japan. matanaka@cis.fukuoka-u.ac.jp
Nakayama
Hiroshi
H
Huruya
Kozaburo
K
Konomi
Ichiro
I
Irie
Shinichiro
S
Kanayama
Akiko
A
Saika
Takeshi
T
Kobayashi
Intetsu
I
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics; D002443:Ceftriaxone / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000187:drug effects / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000235:genetics*; D046915:Penicillin-Binding Proteins / Q000187:drug effects / Q000235:genetics; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D002443:Ceftriaxone; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase