Mat Ghani Nurizati, Hong Kar-Wai, Liew Yvonne Jing Mei, Lau Yin Yin, Yong Hoi-Sen, Tee Kok Keng, Chan Kok-Gan, Chua Kah-Ooi
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia.
Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.
Pathog Glob Health. 2025 Feb-Mar;119(1-2):10-21. doi: 10.1080/20477724.2024.2442194. Epub 2024 Dec 19.
is a multidrug-resistant bacterium that has emerged as a significant nosocomial pathogen globally and renowned for its ability to acquire antimicrobial resistance (AMR) genes. However, understanding of its resistance mechanisms to certain drug classes remains limited. This study focused on four bacterial strains (AB863, AB889, AB930, and AB960) exhibiting carbapenem resistance. They demonstrated high minimum inhibitory concentration (MIC) (128 mg/L) to meropenem and were categorized as extensively drug-resistant strains. Subsequently, they were identified as through 16S rRNA gene sequence analysis and species-specific PCR targeting the -like gene. Three strains were sequenced for their genomes to study the genetic determinants and functional relevance of carbapenem resistance. The draft genome length of the strains ranged from 3.8 to 4.0 Mbp. A total of 16 antibiotic resistance genes including the genes and which mediate carbapenem resistance were identified in the genomes. A comprehensive multilocus sequence typing analysis involving 95 strains from different Asian countries assigned the four strains to sequence type 2 (ST2), the most predominant ST circulating in Asia. Comparative genome analysis also revealed as the most dominant variant of -like gene and also a widespread distribution of gene. In addition, various mobile genetic elements associated with AMR genes and three efflux pumps families were detected in the genomes of the strains. Transformation of and genes resulted in meropenem resistance in the transformant which exhibited a MIC of 2 mg/L, thus confirming direct involvement of both genes in carbapenem resistance.
是一种耐多药细菌,已成为全球重要的医院病原体,并以其获得抗菌药物耐药性(AMR)基因的能力而闻名。然而,对其对某些药物类别的耐药机制的了解仍然有限。本研究聚焦于四株表现出碳青霉烯耐药性的细菌菌株(AB863、AB889、AB930和AB960)。它们对美罗培南表现出高最低抑菌浓度(MIC)(128mg/L),并被归类为广泛耐药菌株。随后,通过16S rRNA基因序列分析和靶向类基因的物种特异性PCR对它们进行了鉴定。对三株菌株进行了全基因组测序,以研究碳青霉烯耐药性的遗传决定因素和功能相关性。这些菌株的基因组草图长度在3.8至4.0Mbp之间。在基因组中总共鉴定出16个抗生素耐药基因,包括介导碳青霉烯耐药性的基因和。一项涉及来自不同亚洲国家的95株菌株的全面多位点序列分型分析将这四株菌株归为序列型2(ST2),这是亚洲最主要流行的ST型。比较基因组分析还揭示类基因的最主要变体以及基因的广泛分布。此外,在这些菌株的基因组中检测到了与AMR基因相关的各种移动遗传元件和三个外排泵家族。和基因的转化导致转化体对美罗培南耐药,其MIC为2mg/L,从而证实这两个基因都直接参与了碳青霉烯耐药性。