Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
Department of Medical Microbiology and Infectious Disease, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
mSphere. 2021 Jan 13;6(1):e01156-20. doi: 10.1128/mSphere.01156-20.
Studies on the epidemiology and genomes of isolates harboring OXA-48-like genes in septicemic neonates are rare. Here, isolates producing these carbapenemases which emerged and persisted in an Indian neonatal unit were characterized in terms of their resistome, transmissibility, and genome diversity. Antibiotic susceptibility and whole-genome sequencing were carried out. The sequence types, resistome, virulome, mobile genetic elements, and transmissibility of carbapenem-resistant plasmids were evaluated. Core genome analysis of isolates was shown in a global context with other OXA-48-like carbapenemase-harboring genomes, including those from neonatal studies. Eleven OXA-48-like carbapenemase-producing (, = 7 and , = 4) isolates belonging to diverse sequence types (ST14, ST15, ST23, ST48, and ST231) were identified. and were found in a high-risk clone, ST14 ( = 4). were in small, nonconjugative ColKP3 plasmids located on truncated Tn, whereas was in self-transmissible, conjugative IncFII plasmids, within truncated Tn Conjugal transfer of was observed in the presence of The study strains were diverse among themselves and showed various levels of relatedness with non-neonatal strains from different parts of the world and similarity with neonatal strains from Tanzania and Ghana when compared with a representative collection of carbapenemase-positive strains. We found that -harboring isolates from a single neonatal unit had remarkably diverse genomes, ruling out clonal spread and emphasizing the extent of plasmid spreading across different STs. This study is probably the first to report the coexistence of and in neonatal isolates. Neonatal sepsis is a leading cause of neonatal mortality in low- and middle-income countries (LMICs). Treatment of sepsis in this vulnerable population is dependent on antimicrobials, and resistance to these life-saving antimicrobials is worrisome. Carbapenemases, enzymes produced by bacteria, can make these antimicrobials useless. Our study describes how OXA-48-like carbapenemases in neonatal septicemic shows remarkable diversity in the genomes of the strains and relatedness with strains from other parts of world and also to some neonatal outbreak strains. It is also the first to describe such resistance due to coproduction of dual carbapenemases, (OXA)-48 and New Delhi metallo-β-lactamase-5, in from neonatal settings. Carbapenemase genes situated on plasmids within high-risk international clones, as seen here, increase the ease and transfer of resistant genetic material. With the WHO treatment protocols not adequately poised to handle such infections, prompt attention to neonatal health care is required.
关于携带 OXA-48 样基因的败血症新生儿分离株的流行病学和基因组研究很少。在此，我们对在印度新生儿病房中出现并持续存在的产这些碳青霉烯酶的分离株的耐药组、可传播性和基因组多样性进行了描述。进行了抗生素敏感性和全基因组测序。评估了耐碳青霉烯类抗生素质粒的序列类型、耐药组、毒力组、移动遗传元件和可传播性。对分离株的核心基因组进行了分析，并与其他携带 OXA-48 样碳青霉烯酶的基因组（包括新生儿研究中的基因组）进行了全球范围内的比较。 共鉴定出 11 株产 OXA-48 样碳青霉烯酶的分离株（, = 7，, = 4），它们属于不同的序列类型（ST14、ST15、ST23、ST48 和 ST231）。 和 在高风险克隆 ST14 中发现（ = 4）。 位于截断的 Tn 上的小非接合性 ColKP3 质粒中，而 位于自我可转移的接合性 IncFII 质粒中，也位于截断的 Tn 中。在存在 的情况下，观察到 的接合转移。研究菌株彼此之间存在多样性，与来自世界各地的非新生儿菌株具有不同程度的相关性，与坦桑尼亚和加纳的新生儿菌株相似，与代表碳青霉烯类阳性 菌株的集合相比。我们发现，来自单个新生儿病房的 携带分离株的基因组差异显著，排除了克隆传播，并强调了质粒在不同 ST 之间传播的程度。这项研究可能是首次报道在新生儿分离株中同时存在 和 。新生儿败血症是中低收入国家（LMICs）新生儿死亡的主要原因。在这个脆弱的人群中，败血症的治疗依赖于抗生素，而对抗这些救命抗生素的耐药性令人担忧。碳青霉烯酶是细菌产生的酶，可以使这些抗生素无效。我们的研究描述了败血症新生儿 中 OXA-48 样碳青霉烯酶在菌株基因组中的多样性以及与来自世界其他地区的菌株的相关性，也与一些新生儿爆发菌株的相关性。这也是首次描述由于同时产生双重碳青霉烯酶（OXA）-48 和新德里金属-β-内酰胺酶-5 而导致的这种耐药性。如这里所见，位于高风险国际克隆内的质粒上的碳青霉烯酶基因增加了耐药遗传物质的传播的便利性和传播性。由于世卫组织的治疗方案还没有充分应对这种感染，因此需要及时关注新生儿保健。
