淋病奈瑟菌 pilQ 基因突变不太可能导致临床淋病分离株对头孢曲松和头孢克肟的敏感性降低。
Alterations of the pilQ gene in Neisseria gonorrhoeae are unlikely contributors to decreased susceptibility to ceftriaxone and cefixime in clinical gonococcal strains.
机构信息
Queensland Children's Medical Research Institute, Children's Health Service District, Brisbane, Queensland, Australia.
出版信息
J Antimicrob Chemother. 2010 Dec;65(12):2543-7. doi: 10.1093/jac/dkq377. Epub 2010 Oct 12.
OBJECTIVES
Gonorrhoea remains a global public health problem and the treatment options are diminishing through the emergence of gonococci resistant to most antimicrobials. Previous in vitro studies have indicated a role for Neisseria gonorrhoeae pilQ alterations in conferring resistance to antimicrobials, including penicillin. In this study, we investigated whether pilQ polymorphisms were associated with decreased susceptibility to extended-spectrum cephalosporins (ESCs) in clinical gonococcal strains.
METHODS
Full-length pilQ nucleotide and PilQ amino acid sequences from geographically and temporally diverse gonococcal clinical isolates (n = 63), including the 2008 WHO reference strains, representing a range of ceftriaxone and cefixime MICs (≤0.008-0.25 and <0.016-0.5 mg/L, respectively) and 38 N. gonorrhoeae multiantigen sequence types, were examined. Previously described alterations associated with decreased ESC susceptibility (mosaic penA, mtrR and penB alterations) were also examined.
RESULTS
Fifteen different pilQ nucleotide sequence types and nine different PilQ amino acid sequence types were observed, with two PilQ types accounting for 53 (84%) of the isolates. Independent of other genetic resistance determinants (penA mosaic, mtrR promoter deletion and penB), only one pilQ alteration, a D526N substitution, provided a statistically significant association with ceftriaxone (P < 0.01) and cefixime (P < 0.05) MICs. However, the two isolates exhibiting D526N lacked all three previously described alterations associated with decreased ESC susceptibility, thereby providing an alternative basis for the low MICs (≤0.008 mg/L) observed for these strains. The previously described E666K (pilQ2) and F595L (pilQ1) mutations were absent in all 63 isolates.
CONCLUSIONS
pilQ polymorphisms are unlikely contributors to decreased susceptibility to ESCs in clinical gonococcal strains.
目的
淋病仍然是一个全球性的公共卫生问题，由于淋病奈瑟菌对抗大多数抗菌药物的耐药性不断出现，治疗选择正在减少。先前的体外研究表明，淋病奈瑟菌 pilQ 改变在对抗抗菌药物（包括青霉素）的耐药性方面发挥作用。在这项研究中，我们研究了 pilQ 多态性是否与临床淋病奈瑟菌株对扩展谱头孢菌素（ESC）的敏感性降低有关。
方法
从地理位置和时间上不同的淋病临床分离株（n=63）中获得全长 pilQ 核苷酸和 PilQ 氨基酸序列，包括代表头孢曲松和头孢克肟 MIC 范围的 2008 年世界卫生组织参考菌株（分别为≤0.008-0.25 和<0.016-0.5mg/L）和 38 种淋病奈瑟菌多抗原序列型，并对先前描述的与 ESC 敏感性降低相关的改变（马赛克 penA、mtrR 和 penB 改变）进行了研究。
结果
观察到 15 种不同的 pilQ 核苷酸序列类型和 9 种不同的 PilQ 氨基酸序列类型，其中两种 PilQ 类型占 53%（84%）的分离株。独立于其他遗传耐药决定因素（penA 马赛克、mtrR 启动子缺失和 penB），只有一种 pilQ 改变，即 D526N 取代，与头孢曲松（P<0.01）和头孢克肟（P<0.05）MICs 具有统计学显著相关性。然而，表现出 D526N 的两种分离株缺乏所有三种先前描述的与 ESC 敏感性降低相关的改变，从而为这些菌株观察到的低 MIC（≤0.008mg/L）提供了替代基础。先前描述的 E666K（pilQ2）和 F595L（pilQ1）突变在所有 63 个分离株中均不存在。
结论
pilQ 多态性不太可能导致临床淋病奈瑟菌株对 ESC 的敏感性降低。
Zotero 插件