High-Throughput Mutagenesis Reveals a Role for Antimicrobial Resistance- and Virulence-Associated Mobile Genetic Elements in Staphylococcus aureus Host Adaptation.
High-Throughput Mutagenesis Reveals a Role for Antimicrobial Resistance- and Virulence-Associated Mobile Genetic Elements in Staphylococcus aureus Host Adaptation.
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DOI：
10.1128/spectrum.04213-22
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发表时间：
2023-02-23
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
耐甲氧西林金黄色葡萄球菌（MRSA）克隆复合物398（CC 398）是欧洲牲畜中占主导地位的牲畜相关（LA）MRSA谱系，并且是难以治疗的人类疾病的日益增加的原因。LA-CC 398 MRSA从不同的人类相关的甲氧西林敏感人群进化而来，从人类到牲畜的这种转变与三个移动的遗传元件（MGE）相关。在这项研究中，我们应用转座子定向插入位点测序（TraDIS），一种高通量转座子诱变方法，以研究有助于LA-CC 398引起人类疾病的遗传特征。我们在人血液中鉴定了26个与LA-CC 398存活相关的基因，在猪血液中鉴定了47个基因。我们对1，180个CC 398分离株进行了系统发育重建，以调查所有鉴定基因的遗传背景。我们发现，所有与人类血液中生存相关的基因都是CC 398核心基因组的一部分，而在猪血液中生存所必需的47个基因中有2个位于MGE上。基因SAPIG 0966位于先前鉴定的携带四环素抗性基因的Tn 916转座子上，该转座子已被证明在LA-CC 398内稳定遗传。基因SAPIG 1525携带在噬菌体元件上，其部分匹配phiSa2wa_st1，phiSa2wa_st1是先前鉴定的携带Panton-Valentine杀白细胞素（PVL）毒力因子的噬菌体。在两株LA-CC 398中构建的基因缺失突变体证实携带Tn 916和SAPIG 1525的SAPIG 0966对CC 398在猪血液中的存活是重要的。我们的研究表明，携带抗菌药物耐药性和毒力基因的MGE可能在血液中的细菌存活中具有次要功能，并且可能对宿主适应很重要。重要性CC 398是欧洲牲畜中耐甲氧西林金黄色葡萄球菌（MRSA）的主要类型，也是人类感染的一个日益增长的原因。先前的研究表明，MRSA CC 398是从人类相关的甲氧西林敏感金黄色葡萄球菌进化而来的，能够快速重新适应人类宿主，同时保持抗生素耐药性。使用高通量转座子诱变，我们的研究确定了26个和47个基因的重要MRSA CC 398生存在人类和猪的血液，分别。MRSA CC 398在猪血液中存活的两个重要基因位于携带抗性或毒力基因的移动的遗传元件（MGE）上。我们的研究表明，这些携带抗菌药物耐药性和毒力基因的MGE可能在血液中的细菌存活中具有次要功能，并且可能对血液感染和宿主适应很重要。
Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex 398 (CC398) is the dominant livestock-associated (LA) MRSA lineage in European livestock and an increasing cause of difficult-to-treat human disease. LA-CC398 MRSA evolved from a diverse human-associated methicillin-sensitive population, and this transition from humans to livestock was associated with three mobile genetic elements (MGEs). In this study, we apply transposon-directed insertion site sequencing (TraDIS), a high-throughput transposon mutagenesis approach, to investigate genetic signatures that contribute to LA-CC398 causing disease in humans. We identified 26 genes associated with LA-CC398 survival in human blood and 47 genes in porcine blood. We carried out phylogenetic reconstruction on 1,180 CC398 isolates to investigate the genetic context of all identified genes. We found that all genes associated with survival in human blood were part of the CC398 core genome, while 2/47 genes essential for survival in porcine blood were located on MGEs. Gene SAPIG0966 was located on the previously identified Tn916 transposon carrying a tetracycline resistance gene, which has been shown to be stably inherited within LA-CC398. Gene SAPIG1525 was carried on a phage element, which in part, matched phiSa2wa_st1, a previously identified bacteriophage carrying the Panton-Valentine leucocidin (PVL) virulence factor. Gene deletion mutants constructed in two LA-CC398 strains confirmed that the SAPIG0966 carrying Tn916 and SAPIG1525 were important for CC398 survival in porcine blood. Our study shows that MGEs that carry antimicrobial resistance and virulence genes could have a secondary function in bacterial survival in blood and may be important for host adaptation. IMPORTANCE CC398 is the dominant type of methicillin-resistant Staphylococcus aureus (MRSA) in European livestock and a growing cause of human infections. Previous studies have suggested MRSA CC398 evolved from human-associated methicillin-sensitive Staphylococcus aureus and is capable of rapidly readapting to human hosts while maintaining antibiotic resistance. Using high-throughput transposon mutagenesis, our study identified 26 and 47 genes important for MRSA CC398 survival in human and porcine blood, respectively. Two of the genes important for MRSA CC398 survival in porcine blood were located on mobile genetic elements (MGEs) carrying resistance or virulence genes. Our study shows that these MGEs carrying antimicrobial resistance and virulence genes could have a secondary function in bacterial survival in blood and may be important for blood infection and host adaptation.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
56.3
作者：
Garcia-Alvarez, Laura;Holden, Matthew T. G.;Lindsay, Heather;Webb, Cerian R.;Brown, Derek F. J.;Curran, Martin D.;Walpole, Enid;Brooks, Karen;Pickard, Derek J.;Teale, Christopher;Parkhill, Julian;Bentley, Stephen D.;Edwards, Giles F.;Girvan, E. Kirsty;Kearns, Angela M.;Pichon, Bruno;Hill, Robert L. R.;Larsen, Anders Rhod;Skov, Robert L.;Peacock, Sharon J.;Maskell, Duncan J.;Holmes, Mark A.
通讯作者：
Holmes, Mark A.
影响因子：
7
作者：
Langridge, Gemma C.;Phan, Minh-Duy;Turner, A. Keith
通讯作者：
Turner, A. Keith
影响因子：
3.7
作者：
Christiansen, Mette T.;Kaas, Rolf S.;Aarestrup, Frank M.
通讯作者：
Aarestrup, Frank M.
在1999年至2011年，丹麦无牲畜接触的患者中，抗甲基肽的金黄色葡萄球菌CC398是疾病的越来越多的原因。
DOI：
10.2807/1560-7917.es.2015.20.37.30021
发表时间：
2015
期刊：
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
影响因子：
--
作者：
Larsen J;Petersen A;Sørum M;Stegger M;van Alphen L;Valentiner-Branth P;Knudsen LK;Larsen LS;Feingold B;Price LB;Andersen PS;Larsen AR;Skov RL
通讯作者：
Skov RL