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对敏感淋球菌人群中对青霉素敏感性与淋病奈瑟菌基因群和特定 PBP2/MtrR/PorB 突变模式的相关性研究。

Association of Neisseria gonorrhoeae genogroups and specific PBP2/MtrR/PorB mutation patterns with susceptibility to penicillin in a susceptible gonococcal population.

机构信息

Department of Microbiology and Immunology, College of Medicine, Saskatoon, Saskatchewan, Canada.

Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), Saskatoon, Saskatchewan, Canada.

出版信息

J Antimicrob Chemother. 2018 Oct 1;73(10):2682-2686. doi: 10.1093/jac/dky233.

DOI:10.1093/jac/dky233
PMID:29992304
Abstract

OBJECTIVES

To ascertain whether the antimicrobial susceptibility of Neisseria gonorrhoeae isolates with differing susceptibilities to penicillin is associated with genogroups (GGs) and combined mutation patterns in PBP2 (penA), the multiple transfer resistance repressor (MtrR; mtrR) and porin B (PorB; porB).

METHODS

The susceptibility of 146 clinical N. gonorrhoeae isolates to penicillin was determined using the agar dilution method and the interpretation criteria of CLSI. The DNA sequences of penA, mtrR and porB in isolates were compared with WT sequences and mutation patterns were determined. Isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and STs were grouped into specific GGs.

RESULTS

The isolates tested carried 9 mutation patterns in PBP2 and 12 mutation patterns in each of MtrR and PorB. Of the 146 isolates, 121 (82.9%) were grouped into 13 different GGs. Isolates with penicillin MICs of 0.03-0.06 mg/L were significantly associated with GG25 (P < 0.05) and PBP2/MtrR/PorB mutation pattern I/WT/WT (P < 0.01). Isolates with a penicillin MIC of 1.0 mg/L were associated (P < 0.05) with: (i) GG3655 and mutation pattern XXII/A-;G45D/G120K;A121N; (ii) GG921 and mutation pattern IX/G45D/G120D;A121N; and (iii) GG1109 and mutation pattern IX/G45D/WT. Sixty percent (9/15) of penicillin-resistant isolates (MIC ≥2 mg/L) were GG3654 (P < 0.0001) and carried mutation pattern IX/G45D/G120K;A121D or IX/G45D/G120D;A121D (P < 0.05).

CONCLUSIONS

Specific mutation patterns in PBP2/MtrR/PorB were associated with specific GGs and penicillin susceptibility. This approach of typing strains and resistance patterns is ideal for predicting antimicrobial resistance and should be used in instances in which gonococcal culture is not available but DNA can be obtained from clinical specimens.

摘要

目的

确定对青霉素敏感性不同的淋病奈瑟菌分离株的抗菌药敏性是否与基因群(GG)以及青霉素结合蛋白 2(PBP2;penA)、多重转移耐药阻遏物(MtrR;mtrR)和孔蛋白 B(PorB;porB)中的联合突变模式有关。

方法

使用琼脂稀释法和 CLSI 的解释标准来确定 146 例临床淋病奈瑟菌分离株对青霉素的敏感性。将分离株的 penA、mtrR 和 porB 的 DNA 序列与 WT 序列进行比较,并确定突变模式。通过淋病奈瑟菌多抗原序列分型(NG-MAST)对分离株进行分型,并将 ST 分为特定的 GG。

结果

测试的分离株在 PBP2 中携带 9 种突变模式,在 MtrR 和 PorB 中各携带 12 种突变模式。在 146 株分离株中,有 121 株(82.9%)分为 13 个不同的 GG。青霉素 MIC 值为 0.03-0.06mg/L 的分离株与 GG25(P<0.05)和 PBP2/MtrR/PorB 突变模式 I/WT/WT(P<0.01)显著相关。青霉素 MIC 值为 1.0mg/L 的分离株与以下情况相关(P<0.05):(i)GG3655 和突变模式 XXII/A-;G45D/G120K;A121N;(ii)GG921 和突变模式 IX/G45D/G120D;A121N;和(iii)GG1109 和突变模式 IX/G45D/WT。60%(9/15)的青霉素耐药分离株(MIC≥2mg/L)为 GG3654(P<0.0001),携带突变模式 IX/G45D/G120K;A121D 或 IX/G45D/G120D;A121D(P<0.05)。

结论

PBP2/MtrR/PorB 中的特定突变模式与特定 GG 和青霉素敏感性相关。这种对菌株和耐药模式进行分型的方法是预测抗菌药物耐药性的理想方法,应在无法进行淋球菌培养但可以从临床标本中获得 DNA 的情况下使用。

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