Hinthong Woranich, Phelan Jody, Hussain Arif, Mazumder Razib, Haq Ihtisham Ul, Ullah Ihsan, Roberts Thomas, Thawong Naphatcha, Billows Nina, Campino Susana, Khan Taj Ali, Mondal Dinesh, Clark Taane G
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Princess Srisavangavadhana Faculty of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Int J Med Microbiol. 2025 Jul 18;320:151666. doi: 10.1016/j.ijmm.2025.151666.
Klebsiella pneumoniae has long posed a significant challenge in clinical settings worldwide, particularly due to its carbapenemase production and multidrug-resistant (MDR) characteristics. While extensive genomic studies of K. pneumoniae have been conducted globally, research in Asia, particularly South Asia, remains limited.
This study aims to address and compare the genomic characteristics of K. pneumoniae isolates from South Asia and Southeast Asia, including virulence, antimicrobial resistance (AMR), plasmids, and mobile genetic elements (MGE) profiles, as well as potential transmission dynamics.
A total of 463 K. pneumoniae genomes were included from collected samples and public databases. All genomes underwent comprehensive analysis, including pan-genome profiling, multi-locus sequence typing (MLST), annotation of virulence factors, AMR genes, plasmids, and MGEs, as well as SNP distance-based analysis to infer transmission dynamics, using established bioinformatic tools.
K. pneumoniae isolates exhibited diverse virulence determinants. Hypervirulent isolates were primarily associated with ST23 and ST86, and commonly harbour aerobactin, salmochelin, and rmpA. The majority of isolates were predicted to be MDR, with those from Southeast Asia showing a higher relative abundance of AMR genes associated with the antibiotic classes examined in this study. Among all isolates, the predominant carbapenemase-associated gene was bla. Col440I_1 was the most prevalent plasmid replicon, although it did not co-occur with any AMR genes. Association between the IncFII_1_pKP9 plasmid replicon and resistance genes sul-5, bla, and bla was found. ISSen9 was the dominant MGE, frequently co-occurring with the plasmid replicons IncFIB(K)_1_Kpn3 and IncFII_1_pKP91. Transmission analysis indicated that the highest isolate similarity occurred within MLST and country. However, clustering based on plasmid replicon profiles revealed that some clusters comprised isolates from multiple countries.
This study provides a comprehensive analysis of the genomic characteristics and transmission patterns of K. pneumoniae in South and Southeast Asia, contributing to our understanding of its virulence and resistance mechanisms. These findings further suggest that plasmid replicons may play a critical role in shaping transmission dynamics and provide valuable insights to inform future AMR surveillance and control strategies.
肺炎克雷伯菌长期以来在全球临床环境中构成重大挑战，尤其是因其产碳青霉烯酶和多重耐药（MDR）特性。虽然全球已对肺炎克雷伯菌进行了广泛的基因组研究，但亚洲，特别是南亚的研究仍然有限。
本研究旨在分析和比较来自南亚和东南亚的肺炎克雷伯菌分离株的基因组特征，包括毒力、抗菌药物耐药性（AMR）、质粒和移动遗传元件（MGE）图谱，以及潜在的传播动态。
从收集的样本和公共数据库中纳入了总共463个肺炎克雷伯菌基因组。使用既定的生物信息学工具对所有基因组进行了全面分析，包括泛基因组分析、多位点序列分型（MLST）、毒力因子注释、AMR基因、质粒和MGE注释，以及基于单核苷酸多态性（SNP）距离的分析以推断传播动态。
肺炎克雷伯菌分离株表现出多样的毒力决定因素。高毒力分离株主要与ST23和ST86相关，并且通常携带气杆菌素、沙门菌素和rmpA。大多数分离株预计为MDR，来自东南亚的分离株在与本研究中检测的抗生素类别相关的AMR基因中显示出较高的相对丰度。在所有分离株中，主要的碳青霉烯酶相关基因是bla。Col440I_1是最常见的质粒复制子，尽管它未与任何AMR基因同时出现。发现IncFII_1_pKP9质粒复制子与耐药基因sul-5、bla和bla之间存在关联。ISSen9是主要的MGE，经常与质粒复制子IncFIB(K)_1_Kpn3和IncFII_1_pKP91同时出现。传播分析表明，分离株之间的最高相似性出现在MLST类型和国家内部。然而，基于质粒复制子图谱的聚类显示，一些聚类包含来自多个国家的分离株。
本研究对南亚和东南亚肺炎克雷伯菌的基因组特征和传播模式进行了全面分析，有助于我们了解其毒力和耐药机制。这些发现进一步表明，质粒复制子可能在塑造传播动态方面发挥关键作用，并为未来的AMR监测和控制策略提供有价值的见解。
