Penicillin-binding proteins are the primary targets for beta lactam drugs, which are main stay of treatment for Streptococcus pneumoniae. The emergence of increased penicillin resistance in meningeal isolates of S. pneumoniae in India is alarming. With this background, we aimed to analyze the pbp gene mutations of penicillin nonsusceptible pneumococcal (PNSP) isolates from within India and their association with international clones. A total of 32 PNSP invasive isolates with a penicillin minimal inhibitory concentrations (MIC) of ≥0.12 μg/mL were subjected to PCR and sequencing for multilocus sequence typing and the pbp genes (pbp2b, pbp2x, and pbp1a). The S. pneumoniae R6 susceptible strain was used as the reference for the comparison analyses. In the majority of the present study isolates, amino acid substitutions were only seen in one of the three active sites of one of the three pbp genes. Thus, pbp genes in the absence of the major substitutions usually associated with penicillin resistance combined with mosaicism in pbp1a resulted in a slight increase in the penicillin MIC to between 0.06 and 2.0 μg/mL, which according to meningeal break point denote resistance. Clonal analyses revealed that the emergence of PNSP in India is due to the gradual expansion of the resistant clones CC320, CC230, and CC63.

中文翻译：

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分析从印度儿童分离的对青霉素不敏感的侵袭性肺炎链球菌中青霉素结合蛋白 1a、2b 和 2x 的氨基酸序列

青霉素结合蛋白是β内酰​​胺类药物的主要靶点，是治疗肺炎链球菌的主要药物。印度肺炎链球菌脑膜分离株出现的青霉素耐药性增加令人担忧。在此背景下，我们旨在分析来自印度境内的青霉素不敏感肺炎球菌 (PNSP) 分离株的pbp基因突变及其与国际克隆的关联。总共32 PNSP侵入分离株的青霉素最小抑菌浓度（MIC）≥ 0.12微克/毫升进行PCR和测序用于多位点序列分型和PBP基因（PBP2B，PBP2X，和pbp1a )。的肺炎链球菌R6敏感菌株被用作用于比较分析的参考。在本研究的大多数分离株中，仅在三个pbp基因之一的三个活性位点之一中看到氨基酸取代。因此，缺乏通常与青霉素抗性相关的主要取代的pbp基因与pbp1a中的嵌合现象相结合，导致青霉素 MIC 略微增加至 0.06 和 2.0 μg/mL 之间，根据脑膜断裂点，这表示抗性。克隆分析表明，印度PNSP的出现是由于抗性克隆CC320、CC230和CC63的逐渐扩大。