来自英格兰和威尔士的产青霉素酶淋病奈瑟菌的blaTEM等位基因的遗传多样性、抗菌药物敏感性及分子流行病学特征
Genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae from England and Wales.
作者信息
Cole Michelle J, Unemo Magnus, Grigorjev Vlad, Quaye Nerteley, Woodford Neil
机构信息
Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK
WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
出版信息
J Antimicrob Chemother. 2015 Dec;70(12):3238-43. doi: 10.1093/jac/dkv260. Epub 2015 Aug 27.
OBJECTIVES
The objective of this study was to investigate the genetic diversity of blaTEM alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates collected in 2012 from England and Wales.
METHODS
PPNG isolates were from the 2012 Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP). Their susceptibility to seven antimicrobials was determined using agar dilution methodology. β-Lactamase production was detected using a nitrocefin test. β-Lactamase plasmid types were determined and blaTEM genes were sequenced. Isolates were also typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST).
RESULTS
Seventy-three PPNG isolates were identified in the 2012 GRASP collection (4.6%, 73/1603). Three different blaTEM alleles were identified, encoding three TEM amino acid sequences: TEM-1 (53%), TEM-1 with a P14S substitution (19%) and TEM-135 (27%). The blaTEM-135 allele was present in nine different NG-MAST types and was found mostly on Asian (60%) and Toronto/Rio (35%) plasmids. By contrast, most TEM-1-encoding plasmids were African (98%). All the TEM-135 isolates displayed high-level ciprofloxacin and tetracycline resistance.
CONCLUSIONS
The high proportion of blaTEM-135 alleles (27%) demonstrates that this variant is circulating within several gonococcal lineages. Only a single specific mutation near the β-lactamase active site could result in TEM-135 evolving into an ESBL. This is concerning particularly because the TEM-135 isolates were associated with high-level ciprofloxacin and tetracycline resistance. It is encouraging that no further TEM alleles were detected in this gonococcal population; however, vigilance is vital as an ESBL in N. gonorrhoeae would render the last remaining option for monotherapy, ceftriaxone, useless.
目的
本研究旨在调查2012年从英格兰和威尔士收集的产青霉素酶淋病奈瑟菌（PPNG）分离株中blaTEM等位基因的遗传多样性、抗菌药物敏感性及分子流行病学特征。
方法
PPNG分离株来自2012年淋病奈瑟菌耐药性监测项目（GRASP）。采用琼脂稀释法测定其对七种抗菌药物的敏感性。使用硝基头孢菌素试验检测β-内酰胺酶的产生。确定β-内酰胺酶质粒类型并对blaTEM基因进行测序。分离株还通过淋病奈瑟菌多抗原序列分型（NG-MAST）进行分型。
结果
在2012年GRASP收集的样本中鉴定出73株PPNG分离株（4.6%，73/1603）。鉴定出三种不同的blaTEM等位基因，编码三种TEM氨基酸序列：TEM-1（53%）、带有P14S替换的TEM-1（19%）和TEM-135（27%）。blaTEM-135等位基因存在于九种不同的NG-MAST类型中，主要存在于亚洲（60%）和多伦多/里约热内卢（35%）质粒上。相比之下，大多数编码TEM-1的质粒来自非洲（98%）。所有TEM-135分离株均表现出对环丙沙星和四环素的高水平耐药。
结论
blaTEM-135等位基因的高比例（27%）表明该变体在多个淋病奈瑟菌谱系中传播。β-内酰胺酶活性位点附近仅一个特定突变就可能导致TEM-135演变为超广谱β-内酰胺酶。这尤其令人担忧，因为TEM-135分离株与环丙沙星和四环素的高水平耐药相关。令人鼓舞的是，在该淋病奈瑟菌群体中未检测到其他TEM等位基因；然而，保持警惕至关重要，因为淋病奈瑟菌中的超广谱β-内酰胺酶会使单药治疗的最后选择头孢曲松变得无用。
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