Ilina Elena N, Vereshchagin Vladimir A, Borovskaya Alexandra D, Malakhova Maja V, Sidorenko Sergei V, Al-Khafaji Nazar C, Kubanova Anna A, Govorun Vadim M
Research Institute of Physico-Chemical Medicine, Moscow, Russian Federation.
Antimicrob Agents Chemother. 2008 Jun;52(6):2175-82. doi: 10.1128/AAC.01420-07. Epub 2008 Mar 31.
The main goal of this work is to clarify the predictive value of known genetic markers of Neisseria gonorrhoeae resistance to penicillin, tetracycline, and fluoroquinolones. The correlation between the presence of certain genetic markers and susceptibility of N. gonorrhoeae isolates to penicillin, tetracycline, and fluoroquinolones has been analyzed by means of statistical methods. Susceptibility testing with penicillin, tetracycline, and fluoroquinolones was performed by the agar dilution method. N. gonorrhoeae genomic DNA was isolated. The presence of bla(TEM-1) and tet(M) genes was analyzed by PCR. A novel method of polymorphism discovery based on a minisequencing reaction followed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry was applied for the analysis of chromosomal N. gonorrhoeae genes involved in antimicrobial resistance development. Clinical N. gonorrhoeae isolates (n = 464) were collected. Susceptibility levels to penicillin, tetracycline, and fluoroquinolones were found to be 25.9%, 35.9%, and 54.1%, respectively. Among the 19 N. gonorrhoeae isolates with penicillin MICs of > or =4 microg/ml, the bla(TEM-1) gene was detected in 12. The Tet(M) determinant was found in 4 of 12 N. gonorrhoeae isolates with tetracycline MICs of > or =16 microg/ml. The chromosomal genetic markers of penicillin and tetracycline resistance were detected especially in isolates with penicillin MICs of 0.25 to 2.0 microg/ml and tetracycline MICs of 0.5 to 4 microg/ml. Mutations in GyrA and ParC were found in 208 of 211 quinolone-resistant N. gonorrhoeae isolates. This work is the first representative molecular research of the N. gonorrhoeae population in Russia. Information about the prevalence of antibiotic resistance mechanisms and the positive predictive value of certain genetic determinants is given. The positive predictive values of the analyzed genetic markers were found to be different for fluoroquinolones (90.3%), penicillin (91.1%), and tetracycline (81.9%).
这项工作的主要目标是阐明淋病奈瑟菌对青霉素、四环素和氟喹诺酮耐药的已知遗传标志物的预测价值。通过统计方法分析了某些遗传标志物的存在与淋病奈瑟菌分离株对青霉素、四环素和氟喹诺酮敏感性之间的相关性。采用琼脂稀释法进行青霉素、四环素和氟喹诺酮的药敏试验。分离淋病奈瑟菌基因组DNA。通过PCR分析bla(TEM-1)和tet(M)基因的存在情况。一种基于微测序反应随后进行基质辅助激光解吸电离飞行时间质谱的新型多态性发现方法被应用于分析参与抗菌药物耐药性产生的淋病奈瑟菌染色体基因。收集了464株临床淋病奈瑟菌分离株。发现对青霉素、四环素和氟喹诺酮的敏感水平分别为25.9%、35.9%和54.1%。在19株青霉素MIC≥4μg/ml的淋病奈瑟菌分离株中，12株检测到bla(TEM-1)基因。在12株四环素MIC≥16μg/ml的淋病奈瑟菌分离株中，4株检测到Tet(M)决定簇。青霉素和四环素耐药的染色体遗传标志物尤其在青霉素MIC为0.25至2.0μg/ml和四环素MIC为0.5至4μg/ml的分离株中检测到。在211株耐喹诺酮淋病奈瑟菌分离株中，208株发现GyrA和ParC基因突变。这项工作是俄罗斯淋病奈瑟菌群体的首次代表性分子研究。给出了抗生素耐药机制的流行情况以及某些遗传决定因素的阳性预测价值的信息。发现所分析的遗传标志物对氟喹诺酮（90.3%）、青霉素（91.1%）和四环素（81.9%）的阳性预测价值不同。
