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全基因组关联研究揭示了与 ST93-IV 型 CA-MRSA 引起的菌血症相关的候选基因。

Genome-wide association studies reveal candidate genes associated to bacteraemia caused by ST93-IV CA-MRSA.

机构信息

Antimicrobial Resistance and Infectious Diseases (AMRID) Research Laboratory, Murdoch University, Murdoch, Western Australia, Australia.

Department of Microbiology, PathWest Laboratory Medicine-WA, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.

出版信息

BMC Genomics. 2021 Jun 5;22(1):418. doi: 10.1186/s12864-021-07738-4.

Abstract

BACKGROUND

The global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to screen for genetic traits that might have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to search for potential virulence genes associated with bacteraemia.

RESULTS

Based on single nucleotide polymorphism phylogenetics we revealed two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002-2017) revealed an observed gain in accessory genes amongst the clone's population. GWAS analysis on the bacteraemia isolates identified two gene candidates that have previously been associated to this kind of infection.

CONCLUSIONS

Although this hypothesis was not tested here, it is possible that the emergence of a ST93-IV clade containing additional virulence genes might be related to the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. More importantly, our data also demonstrated that GWAS can reveal candidate genes for further investigations on the pathogenesis and evolution of MRSA strains within a same lineage.

摘要

背景

社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)在全球范围内的出现,导致了不同地区特定克隆的优势,其中 PVL 阳性 ST93-IV 是澳大利亚主要的 CA-MRSA 克隆。在这项研究中,我们对澳大利亚 ST93-IV 型耐甲氧西林金黄色葡萄球菌(MRSA)基因组进行了全基因组关联研究(GWAS),以筛选可能有助于 ST93-IV 型在澳大利亚持续传播的遗传特征。我们还比较了 ST93-IV 菌血症和非菌血症分离株的基因组,以寻找与菌血症相关的潜在毒力基因。

结果

基于单核苷酸多态性系统发育分析,我们揭示了在澳大利亚同时循环的两个不同的 ST93-IV 克隆群。其中一个克隆群主要包含在澳大利亚北部地区分离的菌株,而第二个克隆群的菌株分布在全国各地。对 ST93-IV 基因组在 15 年期间(2002-2017 年)的可塑性进行分析,发现该克隆种群中观察到附加基因的获得。对菌血症分离株的 GWAS 分析确定了两个先前与这种感染相关的候选基因。

结论

虽然这里没有测试这一假设,但携带更多毒力基因的 ST93-IV 克隆群的出现可能与澳大利亚北部地区土著居民中 ST93-IV 感染的高流行率有关。更重要的是,我们的数据还表明,GWAS 可以揭示候选基因,以进一步研究同一谱系内 MRSA 菌株的发病机制和进化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21c9/8180019/478060dfbd0a/12864_2021_7738_Fig1_HTML.jpg

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