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基于全基因组测序的坦桑尼亚地区转诊医院耐甲氧西林和甲氧西林敏感金黄色葡萄球菌分离株的喹诺酮类药物耐药性特征分析和耐药性检测。

Whole genome sequencing-based characterization and determination of quinolone resistance among methicillin-resistant and methicillin-susceptible S. Aureus isolates from patients attending regional referral hospitals in Tanzania.

机构信息

Kilimanjaro Christian Medical University College (KCMUCo), Kilimanjaro, Tanzania.

Department of Microbiology and Parasitology, State University of Zanzibar (SUZA), Zanzibar, Tanzania.

出版信息

BMC Genomics. 2024 Nov 22;25(1):1130. doi: 10.1186/s12864-024-11045-z.

Abstract

BACKGROUND

The emergence of multidrug-resistant termed Methicillin-resistant Staphylococcus aureus (MRSA) strain, driven by the acquisition of resistance gene mecA imposes a substantial challenge in the treatment and control of their related infections. Although quinolones have historically been effective against both MRSA and methicillin-susceptible S. aureus (MSSA) strains, the rising resistance to quinolones among S. aureus isolates, particularly in MRSA, has severely curtailed their potency and further narrowed down the therapeutic options. This study aimed to determine the burden of MRSA among isolates, as well as their resistance profile, genotypic characterization, and molecular relatedness through the construction of a phylogenetic tree.

MATERIALS AND METHODS

Archived clinical S. aureus isolates from a descriptive, cross-sectional study involving six regional referral hospitals in Dodoma, Songea, Kigoma, Kitete, and Morogoro in the mainland Tanzania and Mnazi Mmoja in Zanzibar were analyzed. Bacterial identification was performed using both classical microbiology and whole genome sequencing on Illumina Nextseq 550 Sequencer. Species identification was done using KmerFinder 3.2, Multilocus Sequence Typing using MLST 2.0, SCCmec typing using SCCmecFinder 1.2, resistance genes using ResFinder 4.1, and phylogenetic relatedness using CSI Phylogeny 1.4.

RESULTS

Out of the 140 isolates analyzed, 69 (49.3%) were identified as MRSA, with 57 (82.6%) exhibiting quinolone resistance. Conversely, 71 isolates were identified as MSSA, and none of them exhibited resistance to quinolones. Spa-typing revealed six spa types, with t355, t1476, and t498 being the most common. Moreover, all (69) MRSA were found to carry SCCmec type IV. The isolates exhibited 14 different sequence types (STs). Notably, ST152 was prevalent among MSSA (50 isolates, 70%), while ST8 was the predominant sequence type among MRSA (58 isolates, 84%). The antimicrobial resistance profile revealed at least three horizontally acquired resistance genes, with blaZ, dfrG, tet(K), and aac (6')-aph (2'') genes being highly prevalent.

CONCLUSION

There is a high genetic diversity among the S. aureus isolates existing in Tanzania regional hospitals, with a concerning burden of quinolone resistance among MRSA isolates. The diversity in resistance genes among MRSA lineages emphasizes the necessity for the development of sustainable antimicrobial stewardship and surveillance to support evidence-based guidelines for managing and controlling MRSA infections in both community and hospital settings.

摘要

背景

由 mecA 耐药基因获得引起的耐甲氧西林金黄色葡萄球菌(MRSA)菌株的出现,对其相关感染的治疗和控制构成了重大挑战。虽然喹诺酮类药物在历史上一直对 MRSA 和甲氧西林敏感的金黄色葡萄球菌(MSSA)菌株有效,但金黄色葡萄球菌分离株对喹诺酮类药物的耐药性不断上升,特别是在 MRSA 中,严重削弱了它们的效力,并进一步缩小了治疗选择范围。本研究旨在通过构建系统发育树,确定 MRSA 在分离株中的负担以及它们的耐药谱、基因分型特征和分子相关性。

材料和方法

对坦桑尼亚大陆的多多马、松盖阿、基特特、基特泰特和莫罗戈罗以及桑给巴尔的姆纳齐莫约六个区域转诊医院进行的描述性横断面研究中的存档临床金黄色葡萄球菌分离株进行了分析。使用经典微生物学和 Illumina Nextseq 550 测序仪上的全基因组测序进行细菌鉴定。使用 KmerFinder 3.2 进行种属鉴定,使用 MLST 2.0 进行多位点序列分型,使用 SCCmecFinder 1.2 进行 SCCmec 分型,使用 ResFinder 4.1 进行耐药基因分型,使用 CSI Phylogeny 1.4 进行系统发育相关性分析。

结果

在分析的 140 株分离株中,有 69 株(49.3%)被鉴定为 MRSA,其中 57 株(82.6%)表现出对喹诺酮类药物的耐药性。相反,有 71 株被鉴定为 MSSA,它们均未对喹诺酮类药物表现出耐药性。Spa 型分析显示有 6 种 spa 型,其中 t355、t1476 和 t498 最为常见。此外,所有(69)株 MRSA 均携带 SCCmec 型 IV。这些分离株表现出 14 种不同的序列类型(ST)。值得注意的是,ST152 在 MSSA 中较为普遍(50 株,70%),而 ST8 是 MRSA 中主要的序列类型(58 株,84%)。抗菌药物耐药谱显示至少有三种水平获得的耐药基因,其中 blaZ、dfrG、tet(K) 和 aac(6')-aph(2'') 基因高度流行。

结论

在坦桑尼亚地区医院存在着高度的金黄色葡萄球菌分离株遗传多样性,并且 MRSA 分离株中存在令人担忧的喹诺酮类药物耐药性。MRSA 谱系中耐药基因的多样性强调了需要制定可持续的抗菌药物管理和监测措施,以支持在社区和医院环境中管理和控制 MRSA 感染的循证指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd3/11583670/c5f7e62f0ab4/12864_2024_11045_Fig1_HTML.jpg

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