Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo.
Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo.
复制标题
金黄色葡萄球菌与鲍曼不动杆菌体内共感染期间的基本健身曲目
DOI：
10.1128/msystems.00338-22
复制
发表时间：
2022-10-26
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
金黄色葡萄球菌是一种主要的人类病原体，经常涉及多种微生物感染。然而，共感染微生物在金黄色葡萄球菌体内的发病机制和适应性必要性中的患病率和作用仍然很大程度上未知。在这项研究中，我们首先对760份临床样本进行了回顾性监测，发现金黄色葡萄球菌和鲍曼不动杆菌合并感染的显著优势。高密度金黄色葡萄球菌转座子突变文库与转座子插入测序（n- seq）结合，进一步确定了一组富含无机离子、氨基酸和碳水化合物代谢的核心基因，这些基因在小鼠全身感染模型中对金黄色葡萄球菌的感染和组织定植至关重要。值得注意的是，我们揭示了金黄色葡萄球菌在组织特异性（肝脏和肾脏）和感染类型特异性（单感染和合并感染）方面对适应度因子的不同需求。与鲍曼不动杆菌的共同感染显著改变了金黄色葡萄球菌在体内的适应性要求；金黄色葡萄球菌Newman菌株中49%的单感染适应度基因被转化为非必需基因，并且在合并感染期间，atp结合盒（ABC）转运体的功能被显著激发。此外，合并感染过程中必需的基因数量（503个）超过了单一感染过程中必需的基因数量（362个）。此外，通过体内竞争实验验证了金黄色葡萄球菌中3种感染型特异性基因在单感染或与鲍曼不动杆菌共感染过程中的作用。我们的数据表明金黄色葡萄球菌和鲍曼不动杆菌合并感染的高发病率和临床相关性，并为建立控制合并感染的抗菌方案提供了新的见解。多微生物感染在临床环境中广泛存在，这可能与感染严重程度的增加和不良的临床结果相关。金黄色葡萄球菌是一种可怕的人类病原体，具有多微生物性，可引起多种疾病。金黄色葡萄球菌的共同感染和相互作用已被描述为与有限的病原体，主要包括铜绿假单胞菌、白色念珠菌和甲型流感病毒。到目前为止，共感染微生物在金黄色葡萄球菌的发病机制和体内适应性必要性中的患病率和作用在很大程度上仍然未知。因此，从群落和全基因组的角度了解多微生物的组成和相互作用，对于阐明金黄色葡萄球菌的发病策略至关重要。我们的研究结果首次证明了金黄色葡萄球菌和鲍曼不动杆菌共同感染的高发病率和临床相关性，说明了多微生物性质在研究金黄色葡萄球菌发病机制中的重要性。感染类型特异性基因可能作为控制金黄色葡萄球菌感染的潜在治疗靶点，无论是在单感染还是合并感染的情况下，为开发控制合并感染的抗菌方案提供了新的见解。
Staphylococcus aureus represents a major human pathogen that is frequently involved in polymicrobial infections. However, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. In this study, we firstly performed a retrospective surveillance of 760 clinical samples and revealed a notable predominance of co-infection with S. aureus and Acinetobacter baumannii. The high-density S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) further identified a core set of genes enriched in metabolism of inorganic ions, amino acids, and carbohydrates, which are essential for infection and tissue colonization of S. aureus in the murine systemic infection model. Notably, we revealed a differential requirement of fitness factors for S. aureus in tissue-specific (liver and kidney) and infection-type-specific manner (mono- and co-infection). Co-infection with A. baumannii dramatically altered the fitness requirements of S. aureus in vivo; 49% of the mono-infection fitness genes in S. aureus strain Newman were converted to non-essential, and the functionality of ATP-binding cassette (ABC) transporters was significantly elicited during co-infection. Furthermore, the number of genes essential during co-infection (503) outnumbers the genes essential during mono-infection (362). In addition, the roles of 3 infection-type-specific genes in S. aureus during mono-infection or co-infection with A. baumannii were validated with competitive experiments in vivo. Our data indicated a high incidence and clinical relevance of S. aureus and A. baumannii co-infection, and provided novel insights into establishing antimicrobial regimens to control co-infections. IMPORTANCE Polymicrobial infections are widespread in clinical settings, which potentially correlate with increased infection severity and poor clinical outcomes. Staphylococcus aureus is a formidable human pathogen that causes a variety of diseases in polymicrobial nature. Co-infection and interaction of S. aureus have been described with limited pathogens, mainly including Pseudomonas aeruginosa, Candida albicans, and influenza A virus. Thus far, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. Understanding the polymicrobial composition and interaction, from a community and genome-wide perspective, is thus crucial to shed light on S. aureus pathogenesis strategy. Here, our findings demonstrated, for the first time, that a high incidence rate and clinical relevance of co-infection was caused by S. aureus and Acinetobacter baumannii, illustrating the importance of polymicrobial nature in investigating S. aureus pathogenesis. The infection-type-specific genes likely serve as potential therapeutic targets to control S. aureus infections, either in mono- or co-infection situation, providing novel insights into the development of antimicrobial regimens to control co-infections.
登录
查看更多内容
影响因子：
6.4
作者：
Goncheva, Mariya, I;Conceicao, Carina;Fitzgerald, J. Ross
通讯作者：
Fitzgerald, J. Ross
影响因子：
6.7
作者：
Alteri CJ;Himpsl SD;Mobley HL
通讯作者：
Mobley HL
影响因子：
30.3
作者：
Keogh D;Tay WH;Ho YY;Dale JL;Chen S;Umashankar S;Williams RBH;Chen SL;Dunny GM;Kline KA
通讯作者：
Kline KA
DOI：
10.1056/nejmoa1306801
发表时间：
2014-03-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Magill SS;Edwards JR;Bamberg W;Beldavs ZG;Dumyati G;Kainer MA;Lynfield R;Maloney M;McAllister-Hollod L;Nadle J;Ray SM;Thompson DL;Wilson LE;Fridkin SK;Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team
通讯作者：
Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team
影响因子：
6.4
作者：
Kong EF;Tsui C;Kucharíková S;Andes D;Van Dijck P;Jabra-Rizk MA
通讯作者：
Jabra-Rizk MA