Loraine Jessica, Heinz Eva, Soontarach Rosesathorn, Blackwell Grace A, Stabler Richard A, Voravuthikunchai Supayang P, Srimanote Potjanee, Kiratisin Pattarachai, Thomson Nicholas R, Taylor Peter W
School of Pharmacy, University College London, London, United Kingdom.
Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Front Microbiol. 2020 Apr 6;11:548. doi: 10.3389/fmicb.2020.00548. eCollection 2020.
Antibiotic resistant strains of are responsible for a large and increasing burden of nosocomial infections in Thailand and other countries of Southeast Asia. New approaches to their control and treatment are urgently needed and an attractive strategy is to remove the bacterial polysaccharide capsule, and thus the protection from the host's immune system. To examine phylogenetic relationships, distribution of capsule chemotypes, acquired antibiotic resistance determinants, susceptibility to complement and other traits associated with systemic infection, we sequenced 191 isolates from three tertiary referral hospitals in Thailand and used phenotypic assays to characterize key aspects of infectivity. Several distinct lineages were circulating in three hospitals and the majority belonged to global clonal group 2 (GC2). Very high levels of resistance to carbapenems and other front-line antibiotics were found, as were a number of widespread plasmid replicons. A high diversity of capsule genotypes was encountered, with only three of these (KL6, KL10, and KL47) showing more than 10% frequency. Almost 90% of GC2 isolates belonged to the most common capsule genotypes and were fully resistant to the bactericidal action of human serum complement, most likely protected by their polysaccharide capsule, which represents a key determinant of virulence for systemic infection. Our study further highlights the importance to develop therapeutic strategies to remove the polysaccharide capsule from extensively drug-resistant during the course of systemic infection.
抗生素耐药菌株在泰国及其他东南亚国家导致了大量且不断增加的医院感染负担。迫切需要新的控制和治疗方法,一种有吸引力的策略是去除细菌的多糖荚膜,从而消除其对宿主免疫系统的保护。为了研究系统发育关系、荚膜化学型分布、获得性抗生素耐药决定因素、对补体的敏感性以及与全身感染相关的其他特征,我们对来自泰国三家三级转诊医院的191株分离株进行了测序,并使用表型分析来表征感染性的关键方面。在这三家医院中循环存在几个不同的谱系,大多数属于全球克隆群2(GC2)。发现对碳青霉烯类和其他一线抗生素的耐药水平非常高,同时还发现了一些广泛存在的质粒复制子。遇到了高度多样的荚膜基因型,其中只有三种(KL6、KL10和KL47)频率超过10%。几乎90%的GC2分离株属于最常见的荚膜基因型,并且对人血清补体的杀菌作用完全耐药,很可能是受到其多糖荚膜的保护,而多糖荚膜是全身感染毒力的关键决定因素。我们的研究进一步强调了在全身感染过程中开发治疗策略以从广泛耐药菌中去除多糖荚膜的重要性。