Novel penA mutations identified in Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan
Novel penA mutations identified in Neisseria gonorrhoeae with decreased susceptibility to ceftriaxone isolated between 2000 and 2014 in Japan
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淋病奈瑟菌中发现新的 penA 突变，对 2000 年至 2014 年间在日本分离的头孢曲松敏感性降低
DOI：
10.1093/jac/dkw161
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
J Antimicrob Chemother
中科院分区：
文献类型：
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作者：
J Antimicrob Chemother
目的检测2000年至2014年日本分离的4株淋病奈瑟菌(GU030113、GU110095、GU110332和GU110362)青霉素耐药相关基因的突变情况。这些菌株的PBP2s与口服头孢菌素敏感性降低相关的PBP2s和先前报道的对头孢曲松敏感性降低的PBP2s相一致。结果GU030113具有PBP2模式X，并附加了A502T的替换。GU110095为PBP2模式XXVII。GU110332具有P552S的额外替换的PBP2模式XXXIV。GU110362的PBP2由模式X(第1~291位氨基酸)和模式V(第292~576位氨基酸)组成。GU030113、GU110095和GU110332的trR启动子有A缺失，PorB1b的G120K和A121D或A121N缺失，PBP1的L421P缺失。GU110362在MtrR阻遏子中有A40D，在PBP1中有L421P。结论GU030113的PBP2模式X增加了A502T，GU110332的PBP2模式XXXIV增加了P552S，可能与头孢曲松的敏感性降低有关。在GU110095和GU110362中，有人认为，除了它们改变的PBP2s之外，外排泵的增强、外膜通透性的降低、β-内酰胺类药物的另一个改变靶点和/或其他未在本研究中发现的机制可能与敏感性降低有关。
ObjectivesWe examined four clinical strains ofNeisseria gonorrhoeae(GU030113, GU110095, GU110332 and GU110362) isolated between 2000 and 2014 in Japan, exhibiting ceftriaxone MICs of 0.5 mg/L, for mutations of the genes associated with penicillin resistance.MethodsThepenA,mtrR,porB1b(penB),ponAandpilQgenes of the strains were sequenced. PBP2s of the strains were aligned to the PBP2s associated with decreased susceptibility to oral cephalosporins, and PBP2s of previously reported strains with decreased susceptibility to ceftriaxone.ResultsGU030113 had PBP2 pattern X with an additional substitution of A502T. GU110095 had PBP2 pattern XXVII. GU110332 had PBP2 pattern XXXIV with an additional substitution of P552S. GU110362 had PBP2 composed of pattern X (amino acid positions 1–291) and pattern V (amino acid positions 292–576). GU030113, GU110095 and GU110332 had deletion of A in themtrRpromoter, G120K and A121D or A121N in PorB1b and L421P in PBP1. GU110362 had A40D in the repressor of MtrR and L421P in PBP1. The strains did not have mutations ofpilQ1andpilQ2.ConclusionsAddition of A502T to PBP2 pattern X in GU030113 and of P552S to PBP2 pattern XXXIV in GU110332 would possibly contribute to decreased susceptibility to ceftriaxone. In GU110095 and GU110362, it was suggested that, in addition to their altered PBP2s, the enhanced efflux pump, reduced permeability in the outer membrane, another altered target of β-lactams and/or other mechanisms not identified in the present study might contribute to decreased susceptibility.