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综合基因组学揭示了来自乌干达国家医院的具有未表征荚膜多糖 K 和脂多糖 O-抗原基因座的多药耐药性产酸克雷伯菌的新型序列类型。

Comprehensive genomics reveals novel sequence types of multidrug resistant Klebsiella oxytoca with uncharacterized capsular polysaccharide K- and lipopolysaccharide O-antigen loci from the National Hospital of Uganda.

机构信息

Department of Microbiology and Immunology, Faculty of Biomedical Sciences, Kampala International University-Western Campus (KIU-WC), Ishaka, Uganda; Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda; Biological and Marine Sciences Unit, Faculty of Science, Marian University College, P. O. Box 47, Bagamoyo, Tanzania; Department of Biomedial Sciences, Didia Education and Health Organization (DEHO), P. O. Box 113, Shinyanga, Tanzania.

Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda; Department of Biomedial Sciences, Didia Education and Health Organization (DEHO), P. O. Box 113, Shinyanga, Tanzania.

出版信息

Infect Genet Evol. 2024 Sep;123:105640. doi: 10.1016/j.meegid.2024.105640. Epub 2024 Jul 11.

Abstract

The Klebsiella oxytoca complex comprises diverse opportunistic bacterial pathogens associated with hospital and community-acquired infections with growing alarming antimicrobial resistance. We aimed to uncover the genomic features underlying the virulence and antimicrobial resistance of isolates from Mulago National Hospital in Uganda. We coupled whole genome sequencing with Pathogenwatch multilocus sequence typing (MLST) and downstream bioinformatic analysis to delineate sequence types (STs) capsular polysaccharide K- and O-antigen loci, along with antimicrobial resistance (AMR) profiles of eight clinical isolates from the National Referral Hospital of Uganda. Our findings revealed that only two isolates (RSM6774 and RSM7756) possess a known capsular polysaccharide K-locus (KL74). The rest carry various unknown K-loci (KL115, KL128, KLI52, KL161 and KLI63). We also found that two isolates possess unknown loci for the lipopolysaccharide O-antigen (O1/O2v1 type OL104 and unknown O1). The rest possess known O1 and O3 serotypes. From MLST, we found four novel sequence types (STs), carrying novel alleles for the housekeeping genes glyceraldehyde-6-phosphate dehydrogenase A (gapA), glucose-6-phosphate isomerase (pgi), and RNA polymerase subunit beta (rpoB). Our AMR analysis revealed that all the isolates are resistant to ampicillin and ceftriaxone, with varied resistance to other antibiotics, but all carry genes for extended-spectrum beta-lactamases (ESBLs). Notably, one strain (RSM7756) possesses outstanding chromosomal and plasmid-encoded AMR to beta-lactams, cephalosporins, fluoroquinolones and methoprims. Conclusively, clinical samples from Mulago National Referral Hospital harbor novel STs and multidrug resistant K. oxytoca strains, with significant public health importance, which could have been underrated.

摘要

产酸克雷伯菌复合体包含多种与医院和社区获得性感染相关的机会性病原体,其对抗微生物药物的耐药性日益令人担忧。我们旨在揭示乌干达穆拉戈国家医院分离株的毒力和抗微生物药物耐药性的基因组特征。我们将全基因组测序与病原体监测多位点序列分型(MLST)和下游生物信息学分析相结合,以描绘序列型(ST)荚膜多糖 K-和 O-抗原基因座,以及乌干达国家转诊医院的 8 株临床分离株的抗微生物药物耐药(AMR)图谱。我们的研究结果表明,只有 2 株分离株(RSM6774 和 RSM7756)具有已知的荚膜多糖 K-基因座(KL74)。其余的携带各种未知的 K-基因座(KL115、KL128、KLI52、KL161 和 KLI63)。我们还发现,2 株分离株具有未知的脂多糖 O-抗原(O1/O2v1 型 OL104 和未知 O1)基因座。其余的携带已知的 O1 和 O3 血清型。通过 MLST,我们发现了 4 种新的序列型(ST),它们携带与管家基因甘油醛-6-磷酸脱氢酶 A(gapA)、葡萄糖-6-磷酸异构酶(pgi)和 RNA 聚合酶亚基β(rpoB)相关的新等位基因。我们的抗微生物药物耐药性分析表明,所有分离株对氨苄西林和头孢曲松均具有耐药性,对其他抗生素的耐药性也各不相同,但均携带超广谱β-内酰胺酶(ESBLs)基因。值得注意的是,一株分离株(RSM7756)对β-内酰胺类、头孢菌素类、氟喹诺酮类和甲氧嘧啶类药物具有出色的染色体和质粒编码的抗微生物药物耐药性。总之,穆拉戈国家转诊医院的临床样本中存在新型 ST 和多药耐药的产酸克雷伯菌,具有重要的公共卫生意义,但可能被低估了。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e6/11415533/b58a870cac1a/nihms-2021110-f0001.jpg

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