Polymorphism in ftsI gene and β-lactam susceptibility in Portuguese Haemophilus influenzae strains: clonal dissemination of β-lactamase-positive isolates with decreased susceptibility to amoxicillin/clavulanic acid
Polymorphism in ftsI gene and β-lactam susceptibility in Portuguese Haemophilus influenzae strains: clonal dissemination of β-lactamase-positive isolates with decreased susceptibility to amoxicillin/clavulanic acid
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DOI：
10.1093/jac/dkq533
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发表时间：
2011-04-01
影响因子：
5.2
通讯作者：
Bajanca-Lavado, Maria Paula
中科院分区：
文献类型：
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作者：
Barbosa, Ana Raquel;Giufre, Maria;Bajanca-Lavado, Maria Paula
目的：本研究的目的是描述葡萄牙流感嗜血杆菌临床分离株的氨苄西林耐药机制。研究青霉素结合蛋白3（PBP 3）的特异性氨基酸取代模式（有或无β-内酰胺酶产生）与β-内酰胺类药物敏感性的关系以及菌株间的遗传相关性。分析了根据不同氨苄青霉素MIC选择的流感分离株[101株不产生β-内酰胺酶的氨苄青霉素耐药（BLNAR）分离株、80株产生β-内酰胺酶的氨苄青霉素耐药（BLPAR）分离株和59株不产生β-内酰胺酶的氨苄青霉素敏感（BLNAS）分离株]。PCR检测β-内酰胺酶编码基因bla（TEM-1）。对编码PBP 3的ftsI基因进行测序。结果：240株H.在流感病毒分离株中，141株在ftsI基因的转肽酶结构域中有突变，包括大多数BLNAR菌株（94/101，93.1%）和高百分比的BLPAR菌株（47/80，58.8%）。如前所述，后者被描述为β-内酰胺酶阳性阿莫西林/克拉维酸耐药（BLPACR）。在KTG基序附近发现了最常见的氨基酸取代：N526 K（136/141，96.5%）、V547 I（124/141，87.9%）和N569 S（121/141，85.8%）。将141株菌株分为31种ftsI突变模式，包括6组（I、IIa、IIb、IIc、IId和类III）。BLNAR菌株具有遗传多样性，但BLPACR菌株之间的亲缘关系较近。结论：本研究表明，β-内酰胺类抗生素耐药的非酶机制在H.流感病毒在葡萄牙BLPACR菌株的克隆传播显示出对氨苄青霉素的高耐药性和对阿莫西林/克拉维酸的敏感性降低。
Objectives: The aim of this study was to characterize ampicillin resistance mechanisms in clinical isolates of Haemophilus influenzae from Portugal. Association between specific patterns of amino acid substitutions in penicillin-binding protein 3 (PBP3) (with or without beta-lactamase production) and beta-lactam susceptibility as well as genetic relatedness among isolates were investigated.Methods: Two-hundred and forty non-consecutive H. influenzae isolates chosen according to their different ampicillin MICs [101 beta-lactamase-non-producing ampicillin-resistant (BLNAR) isolates, 80 beta-lactamase-producing ampicillin-resistant (BLPAR) isolates and 59 b-lactamase-non-producing ampicillin-susceptible (BLNAS) isolates] were analysed. The beta-lactamase-encoding bla(TEM-1) gene was detected by PCR. The ftsI gene encoding PBP3 was sequenced. Genetic relatedness among isolates was examined by PFGE.Results: Of the 240 H. influenzae isolates, 141 had mutations in the transpeptidase domain of the ftsI gene, including most BLNAR strains (94/101, 93.1%) and a high percentage of BLPAR strains (47/80, 58.8%). As previously reported, the latter have been described as beta-lactamase-positive amoxicillin/clavulanic acid resistant (BLPACR). The most common amino acid substitutions were identified near the KTG motif: N526K (136/141, 96.5%), V547I (124/141, 87.9%) and N569S (121/141, 85.8%). The 141 strains were divided into 31 ftsI mutation patterns and included six groups (I, IIa, IIb, IIc, IId and III-like). BLNAR strains were genetically diverse but close genetic relationships were demonstrated among BLPACR strains.Conclusions: This study shows that the non-enzymatic mechanism of resistance to beta-lactams is widespread among H. influenzae isolates in Portugal. Clonal dissemination of BLPACR strains showing high resistance to ampicillin and reduced susceptibility to amoxicillin/clavulanic acid was documented.