Various penA mutations together with mtrR, porB and ponA mutations in Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone
Various penA mutations together with mtrR, porB and ponA mutations in Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone
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DOI：
10.1093/jac/dkp505
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发表时间：
2010-04-01
影响因子：
5.2
通讯作者：
Lee, Kyungwon
中科院分区：
文献类型：
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作者：
Lee, Sang-Guk;Lee, Hyukmin;Lee, Kyungwon
为了解淋球菌PenA、mtrR、porB、PONA和PilQ基因突变与头孢菌素耐药的关系，选择对头孢克肟和头孢曲松敏感性降低的淋球菌46株(MICs>；=0.12 mg/L)和2株敏感株。分析了PenA的全序列和以前报道的其他基因的热点突变位点的部分序列。淋病奈瑟菌多抗原序列分型(NG-MAST)结果显示，单个分离株含有一个嵌合型青霉素结合蛋白2(PBP2)，其头孢克肟MIC值最高(0.5 mg/L)。对头孢菌素类药物敏感性降低的菌株大多含有非嵌合体的PBP-2序列，其中PBP-2模式XIII最为常见(28/46)。所有对头孢菌素敏感性降低的菌株也都有mtrr和porB突变。2株敏感菌株具有PBP2型XIV和不完全MTRR蛋白，这是一个新的突变。具有相同PBP 2模式的分离株包括多种NG-MAST序列类型。淋球菌对头孢曲松和头孢克辛的敏感性降低与不同的PenA突变有关，特别是PBP 2模式XIII包含Ala-501->；Val替换，以及mtrR和porB突变。只有一株具有马赛克Pena序列的菌株的存在表明，韩国对头孢曲松和头孢克辛的耐药性大多与马赛克Pena序列无关。高度异质性的NG-MAST序列类型排除了特定亚型的克隆性扩展。
To examine mutations within the penA, mtrR, porB, ponA and pilQ genes of Neisseria gonorrhoeae to determine their contribution to cephalosporin resistance.A total of 46 N. gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone (MICs >= 0.12 mg/L) and two susceptible isolates were selected. The full sequence of penA and partial sequences previously reported as hot mutation sites of the other genes were analysed. Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed.A mosaic penicillin-binding protein 2 (PBP 2) was found in a single isolate that exhibited the highest cefixime MIC (0.5 mg/L). The majority of the isolates with reduced susceptibility to cephalosporins contained non-mosaic PBP 2 sequences, of which PBP 2 pattern XIII was most common (28/46). All isolates with reduced susceptibility to cephalosporins also had mtrR and porB mutations. Two susceptible isolates had the PBP 2 pattern XIV and an incomplete MtrR protein, which was a new mutation. Isolates with identical PBP 2 patterns comprised multiple NG-MAST sequence types.Reduced susceptibility of N. gonorrhoeae to ceftriaxone and cefixime was associated with diverse penA mutations, particularly PBP 2 pattern XIII containing an Ala-501 -> Val substitution, together with mtrR and porB mutations. The existence of only one strain having the mosaic penA sequence indicated that ceftriaxone and cefixime resistance in Korea is mostly not associated with a mosaic penA sequence. Highly heterogeneous NG-MAST sequence types excluded the clonal expansion of a particular subtype.