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南非血流感染中致病性多重耐药肺炎克雷伯菌和产酸克雷伯菌的基因组分析

Genomic analysis of virulent, multidrug resistant Klebsiella pneumoniae and Klebsiella oxytoca from bloodstream infections, South Africa.

作者信息

Hetsa Bakoena A, Asante Jonathan, Mbanga Joshua, Amoako Daniel G, Abia Akebe L K, Ismail Arshad, Essack Sabiha Y

机构信息

Antimicrobial Research Unit, College of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa.

Antimicrobial Research Unit, College of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa; School of Pharmacy and Pharmaceutical Sciences, University of Cape Coast, PMB, Cape Coast, Ghana.

出版信息

Microb Pathog. 2025 Mar;200:107272. doi: 10.1016/j.micpath.2024.107272. Epub 2025 Jan 8.

DOI:10.1016/j.micpath.2024.107272
PMID:39793677
Abstract

UNLABELLED

The study investigated the resistome, virulome and mobilome of multidrug resistant (MDR) Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates.

METHODS

A total of 46 suspected Klebsiella species (spp.) were collected from blood cultures within the uMgungundlovu District in the KwaZulu-Natal Province. Antibiotic susceptibility was determined against a panel of 19 antibiotics using the disk diffusion test. A subset of 14 MDR K. pneumoniae (n = 10) and K. oxytoca (n = 4) isolates were selected based on their antibiograms and subjected to whole genome sequencing (WGS). The sequence types (STs), resistome, virulome, mobilome, capsule loci (KLs) were analysed using relevant WGS and bioinformatics tools.

RESULTS

Of the 10 K. pneumoniae sequence types (ST) identified, the most common were ST25 (n = 3), ST101 (n = 3), and 4 K. oxytoca belonged to ST450 (n = 3). The two high-risk K. pneumoniae clones ST15, and ST17 were identified. O and K capsule types were identified, with predominance of KL2, KL17, KL29, O1/O2v2, O1/O2v1, and OL104 respectively. The majority of isolates displayed multidrug resistance predominantly carrying β-lactamase genes, including bla, bla, bla and bla, and bla including the carbapenemase bla in two (14.3 %) study isolates. Other resistance genes included: aac(6')-lb-cr, aac(3), aac, aph, aad, dfr, tet(A), and tet(D), mph(A), sul1, sul2, oqx, qnr, acrR, ramR, parC, gyrA, arr-3, cat, fosA, qacE genes conferring resistance to aminoglycosides, trimethoprim, tetracycline, macrolide, sulfonamides, fluoroquinolones, rifampicin phenicols, fosfomycin, and quaternary ammonium compound disinfectant. Virulence factors related to hypervirulence: encoding aerobactin (iuc, iutA), salmochelin (iro), yersiniabactin (ybt), enterobactin (ent), type 1 and 3 (mrk and fim), and capsule synthesis (rcsA and rcsB) were identified. IncF, IncR, and Col plasmid replicon types and class I integrons were detected, with IncFIB(K) predominance. The bla and bla genes were bracketed by Tn3 transposons, ISEc9, recombinase and IS91 insertion sequences.

CONCLUSIONS

The convergence of multidrug resistance and hypervirulence genes in Klebsiella strains is a potential clinical concern. Carbapenemase, ESBL screening and genomic surveillance are urgently required in hospital environments.

摘要

未标注

本研究调查了多重耐药(MDR)肺炎克雷伯菌和产酸克雷伯菌临床分离分离的耐药基因组、毒力基因组和可移动基因组。

方法

从夸祖鲁-纳塔尔省乌姆贡德洛武区的血培养物中总共收集了46株疑似克雷伯菌属菌株。使用纸片扩散法测定对一组19种抗生素的药敏性。根据药敏谱选择了14株MDR肺炎克雷伯菌(n = 10)和产酸克雷伯菌(n = 4)分离株的子集,并进行全基因组测序(WGS)。使用相关的WGS和生物信息学工具分析序列类型(STs)、耐药基因组、毒力基因组、可移动基因组、荚膜位点(KLs)。

结果

在鉴定出的10种肺炎克雷伯菌序列类型(ST)中,最常见的是ST25(n = 3)、ST101(n = 3),4株产酸克雷伯菌属于ST450(n = 3)。鉴定出了两种高风险肺炎克雷伯菌克隆ST15和ST17。鉴定出了O和K荚膜类型,分别以KL2、KL17、KL29、O1/O2v2、O1/O2v1和OL104为主。大多数分离株表现出多重耐药,主要携带β-内酰胺酶基因,包括bla、bla、bla和bla,以及bla,其中两株(14.3%)研究分离株携带碳青霉烯酶bla。其他耐药基因包括:赋予对氨基糖苷类、甲氧苄啶、四环素、大环内酯类、磺胺类、氟喹诺酮类、利福平、酚类、磷霉素和季铵化合物消毒剂耐药性的aac(6')-lb-cr、aac(3)、aac、aph、aad、dfr、tet(A)、tet(D)、mph(A)、sul1、sul2、oqx、qnr、acrR、ramR、parC、gyrA、arr-3、cat、fosA、qacE基因。鉴定出了与高毒力相关的毒力因子:编码气杆菌素(iuc、iutA)、沙门菌素(iro)、耶尔森菌素(ybt)、肠杆菌素(ent)、1型和3型菌毛(mrk和fim)以及荚膜合成(rcsA和rcsB)。检测到IncF、IncR和Col质粒复制子类型以及I类整合子,以IncFIB(K)为主。bla和bla基因被Tn3转座子、ISEc9、重组酶和IS91插入序列包围。

结论

克雷伯菌菌株中多重耐药和高毒力基因的汇聚是一个潜在的临床问题。医院环境中迫切需要进行碳青霉烯酶、超广谱β-内酰胺酶筛查和基因组监测。

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