Human Urine Alters Methicillin-Resistant Staphylococcus aureus Virulence and Transcriptome
Human Urine Alters Methicillin-Resistant Staphylococcus aureus Virulence and Transcriptome
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DOI：
10.1128/aem.00744-21
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发表时间：
2021-08-01
影响因子：
4.4
通讯作者：
Kulkarni, Ritwij
中科院分区：
文献类型：
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作者：
Paudel, Santosh;Bagale, Kamal;Kulkarni, Ritwij
革兰氏阳性耐甲氧西林金黄色葡萄球菌（MRSA）是医院相关性尿路感染（UTI）的一种新兴原因，尤其是在导管插入患者中。尽管很罕见，但MRSA UTI容易发生潜在的危及生命的恶化，如菌血症，这可能是常规抗生素治疗难以治愈的。为了阐明MRSA泌尿系致病的分子机制，我们暴露了三种S。金黄色葡萄球菌临床分离株，包括2株MRSA菌株，与人尿液接触2 h，分析其毒力特征和基因表达变化。体外毒力试验表明，人尿迅速改变粘附人膀胱上皮细胞和纤连蛋白，绵羊红细胞（RBC 5）的溶血，和表面疏水性的葡萄球菌菌株特异性的方式。此外，尿路致病性菌株MRSA-1369的转录组测序（RNA-Seq）分析显示，2小时长的暴露于人尿液通过修饰编码催化代谢途径、毒力因子和转录调节因子的酶的基因表达来改变MRSA转录组。总之，我们的研究结果提供了重要的见解，人类尿液如何专门和迅速改变MRSA的生理和促进MRSA的生存在营养有限和敌对的泌尿微environment.IMPORTANCE耐甲氧西林金黄色葡萄球菌（MRSA）是一种罕见的原因尿路感染（UTI）在一般人群。然而，重要的是要了解MRSA的病理生理学在泌尿道，因为分离的MRSA尿液样本往往先于潜在的危及生命的MRSA菌血症。在这份报告中，我们描述了如何暴露于人类尿液改变MRSA的全球基因表达和毒力。我们假设这些改变可能有助于MRSA适应尿路内营养限制性、免疫敌对性条件，导致MRSA UTI。
Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of hospital-associated urinary tract infections (UTI), especially in catheterized individuals. Despite being rare, MRSA UTI are prone to potentially life-threatening exacerbations such as bacteremia that can be refractory to routine antibiotic therapy. To delineate the molecular mechanisms governing MRSA urinary pathogenesis, we exposed three S. aureus clinical isolates, including two MRSA strains, to human urine for 2 h and analyzed virulence characteristics and changes in gene expression. The in vitro virulence assays showed that human urine rapidly alters adherence to human bladder epithelial cells and fibronectin, hemolysis of sheep red blood cells (RBC5), and surface hydrophobicity in a staphylococcal strain-specific manner. In addition, transcriptome sequencing (RNA-Seq) analysis of uropathogenic strain MRSA-1369 revealed that 2-h-long exposure to human urine alters MRSA transcriptome by modifying expression of genes encoding enzymes catalyzing metabolic pathways, virulence factors, and transcriptional regulators. In summary, our results provide important insights into how human urine specifically and rapidly alters MRSA physiology and facilitates MRSA survival in the nutrient-limiting and hostile urinary microenvironment.IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon cause of urinary tract infections (UTI) in the general population. However, it is important to understand MRSA pathophysiology in the urinary tract because isolation of MRSA in urine samples often precedes potentially life-threatening MRSA bacteremia. In this report, we describe how exposure to human urine alters MRSA global gene expression and virulence. We hypothesize that these alterations may aid MRSA in acclimating to the nutrient-limiting, immunologically hostile conditions within the urinary tract leading to MRSA UTI.