Molecular epidemiology of 16S rRNA methyltransferase in Brazil: RmtG in Klebsiella aerogenes ST93 (CC4)

Abstract Aminoglycosides are a class of antibiotics that play a key role in antimicrobial treatment of Multidrug resistant (MDR) Gram-negative bacilli, typically in combination with β-lactams. Ribosomal 16S RNA modification by methyltransferases (e.g. RmtG) is an aminoglycoside resistance mechanism that, along with the occurrence carbapenem-resistant Enterobacteriaceae (CRE), has become a clinical concern. In Brazil, rmtG genes were initially reported in Klebsiella pneumoniae, and monitoring isolates from other species carrying this gene is critical for epidemiological studies and to prevent dissemination. Here we report the presence of rmtG in Klebisella aerogenes D3 and characterize its genetic context in comparison to isolates from other species. Further, we performed a phylogenetic reconstruction of 900 16S rRNA methyltransferases (16S-RMTases) and methyltransferase-related proteins. We show that, in K. aerogenes D3, rmtG co-occurs with sul2, near a transposon with an IS91-like insertion sequence. Resistome analysis revealed the co-production of RmtG and CTX-M-59. Ongoing surveillance of 16S-RMTases is crucial to delay the dissemination of such multiresistant isolates. Our results also highlight the reduction in treatment options for CRE infections, as well as the need of expanding prevention measures of these pathogens worldwide.

摘要：氨基糖苷类抗生素（Aminoglycosides）是一类在多重耐药（Multidrug resistant, MDR）革兰阴性杆菌的抗菌治疗中发挥关键作用的抗生素，通常与β-内酰胺类（β-lactams）联合使用。通过甲基转移酶（methyltransferases，如RmtG）对核糖体16S RNA进行修饰，是一种氨基糖苷类耐药机制，该机制与碳青霉烯类耐药肠杆菌科（carbapenem-resistant Enterobacteriaceae, CRE）的出现一同成为临床关注的焦点。在巴西，rmtG基因最初于肺炎克雷伯菌（Klebsiella pneumoniae）中被报道，对携带该基因的其他物种分离株进行监测对于流行病学研究及预防其传播至关重要。本研究报道了产气克雷伯菌（Klebsiella aerogenes）D3中rmtG的存在，并与其他物种的分离株对比，对其遗传背景进行了表征。此外，我们对900种16S rRNA甲基转移酶（16S rRNA methyltransferases, 16S-RMTases）及甲基转移酶相关蛋白进行了系统发育重建。结果显示，在产气克雷伯菌D3中，rmtG与sul2共存，并定位于带有IS91样插入序列的转座子附近。耐药组（Resistome）分析揭示了RmtG与CTX-M-59的共产生现象。持续监测16S-RMTases对于延缓此类多重耐药分离株的传播至关重要。本研究结果同时凸显了碳青霉烯类耐药肠杆菌科感染治疗选择的减少，以及在全球范围内加强此类病原体防控措施的必要性。