Commensal Streptococci Serve as a Reservoir for β-Lactam Resistance Genes in Streptococcus pneumoniae
Commensal Streptococci Serve as a Reservoir for β-Lactam Resistance Genes in Streptococcus pneumoniae
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DOI：
10.1128/aac.00429-15
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发表时间：
2015-06-01
影响因子：
4.9
通讯作者：
Kilian, Mogens
中科院分区：
文献类型：
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作者：
Jensen, Anders;Valdorsson, Oskar;Kilian, Mogens
肺炎链球菌是肺炎、脑膜炎、败血症和中耳感染的主要原因。对青霉素不敏感的肺炎链球菌分离株的发病率在世界范围内有所上升，在一些国家可能超过 20%。肺炎球菌中的 β-内酰胺抗生素耐药性与青霉素结合蛋白 (PBP) 的显着序列多态性相关。共生链球菌，特别是轻链球菌和口腔链球菌，已被确定为突变基因片段的推定供体。然而，没有研究比较大量共生链球菌和肺炎链球菌中所涉及的 pbp 基因的序列。因此，我们分别在107、96和88个共生链球菌敏感菌株和非敏感菌株中研究了三个pbp基因pbp2x、pbp2b和pbp1a的转肽酶区域在核苷酸和氨基酸水平上的序列多样性，以确定共生链球菌和肺炎链球菌之间的同源重组在多大程度上在β-内酰胺耐药性的发展中发挥作用。肺炎链球菌。与肺炎球菌相反，在共生链球菌的敏感和非敏感菌株中观察到 pbp2x、pbp2b 和 pbp1a 的转肽酶区域存在广泛的序列变异，这可能反映了共生链球菌许多进化谱系的遗传多样性以及物种内和物种间同源物发生的重组事件。我们的数据支持这样的观点，即肺炎球菌对 β-内酰胺抗生素的耐药性是由于从共生 Mitis 组链球菌，尤其是 S. mitis 获得的序列所致。然而，先前与肺炎球菌中的β-内酰胺耐药性相关的几种氨基酸改变似乎代表了供体菌株的物种特征，而不是耐药性的原因。
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and middle ear infections. The incidence of S. pneumoniae isolates that are not susceptible to penicillin has risen worldwide and may be above 20% in some countries. Beta-lactam antibiotic resistance in pneumococci is associated with significant sequence polymorphism in penicillin-binding proteins (PBPs). Commensal streptococci, especially S. mitis and S. oralis, have been identified as putative donors of mutated gene fragments. However, no studies have compared sequences of the involved pbp genes in large collections of commensal streptococci with those of S. pneumoniae. We therefore investigated the sequence diversity of the transpeptidase region of the three pbp genes, pbp2x, pbp2b, and pbp1a in 107, 96, and 88 susceptible and nonsusceptible strains of commensal streptococci, respectively, at the nucleotide and amino acid levels to determine to what extent homologous recombination between commensal streptococci and S. pneumoniae plays a role in the development of beta-lactam resistance in S. pneumoniae. In contrast to pneumococci, extensive sequence variation in the transpeptidase region of pbp2x, pbp2b, and pbp1a was observed in both susceptible and nonsusceptible strains of commensal streptococci, conceivably reflecting the genetic diversity of the many evolutionary lineages of commensal streptococci combined with the recombination events occurring with intra-and inter species homologues. Our data support the notion that resistance to beta-lactam antibiotics in pneumococci is due to sequences acquired from commensal Mitis group streptococci, especially S. mitis. However, several amino acid alterations previously linked to beta-lactam resistance in pneumococci appear to represent species signatures of the donor strain rather than being causal of resistance.