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巴塞罗那淋病奈瑟菌的抗菌药物敏感性:penA、ponA、mtrR和porB基因突变以及与头孢菌素敏感性降低相关的NG-MAST序列类型

Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins.

作者信息

Serra-Pladevall J, Barberá M J, Rodriguez S, Bartolomé-Comas R, Roig G, Juvé R, Andreu A

机构信息

Microbiology Department, Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron, 119-129, 08035, Barcelona, Spain.

Genetics and Microbiology Department, Universitat Autonoma de Barcelona, Cerdanyola, Spain.

出版信息

Eur J Clin Microbiol Infect Dis. 2016 Sep;35(9):1549-56. doi: 10.1007/s10096-016-2696-7. Epub 2016 Jun 2.

DOI:10.1007/s10096-016-2696-7
PMID:27255221
Abstract

The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 μg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 μg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu → Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC ≥ 0.125 μg/mL) was observed for these four genes. Of the 48 strains with an MIC ≥ 0.125 μg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC ≥ 0.125 μg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance.

摘要

本研究的目的是确定我们地区淋病奈瑟菌(NG)的抗菌药物敏感性,分析头孢菌素耐药的分子机制,并对我们的NG菌株进行分子分型。使用Etest测定抗菌药物敏感性。研究了penA、mtrR、penB和ponA基因。通过淋病奈瑟菌多抗原序列分型进行分子分型。在2013年分析的329株菌株中,没有一株显示出高水平的头孢菌素耐药性,但8.2%对头孢克肟耐药[最低抑菌浓度(MIC)>0.125μg/mL],0.6%对头孢曲松耐药(MIC>0.125μg/mL)。阿奇霉素耐药率为4.3%,环丙沙星耐药率为49.2%。在48株对头孢克肟MIC≥0.125μg/mL的菌株中,58.3%显示penA镶嵌型XXXIV,98%在ponA基因第421位有Leu→Pro替换,100%在PorB1b孔蛋白第101和102位有氨基酸变化,87.5%的菌株在MtrC-D-E外排泵启动子区域有腺嘌呤缺失。对于这四个基因,头孢菌素敏感性降低(MIC≥0.125μg/mL)的菌株与未降低的菌株之间存在显著差异。在48株对头孢克肟MIC≥0.125μg/mL的菌株中,43.8%属于基因群G1407,27.1%属于基因群G2400。发现G1407与敏感性降低(MIC≥0.125μg/mL)显著相关,G2992与敏感性显著相关,并且G1407与镶嵌型XXXIV之间以及G2400与penA中的A501T替换之间也存在显著关联。我们地区的NG耐药率高于欧洲中位数。我们检测到G2400的出现,其可能是抗菌药物耐药性的一个来源。

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