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牙龈卟啉单胞菌酪氨酸激酶是多微生物感染中的适应性决定因素。

Porphyromonas gingivalis Tyrosine Kinase Is a Fitness Determinant in Polymicrobial Infections.

机构信息

Department of Oral Immunology and Infectious Diseases, University of Louisvillegrid.266623.5, Louisville, Kentucky, USA.

Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy and Health Sciences, Louisville, Kentucky, USA.

出版信息

Infect Immun. 2022 Jun 16;90(6):e0017022. doi: 10.1128/iai.00170-22. Epub 2022 May 16.

Abstract

Many pathogenic microbial ecosystems are polymicrobial, and community function can be shaped by interbacterial interactions. Little is known, however, regarding the genetic determinants required for fitness in heterotypic community environments. In periodontal diseases, Porphyromonas gingivalis is a primary pathogen, but only within polymicrobial communities. Here, we used a transposon sequencing (Tn-Seq) library of P. gingivalis to screen for genes that influence fitness of the organism in a coinfection murine abscess model with the oral partner species Streptococcus gordonii and Fusobacterium nucleatum. Genes impacting fitness with either organism were involved in diverse processes, including metabolism and energy production, along with cell wall and membrane biogenesis. Despite the overall similarity of function, the majority of identified genes were specific to the partner species, indicating that synergistic mechanisms of P. gingivalis vary to a large extent according to community composition. Only two genes were identified as essential for P. gingivalis fitness in abscess development with both S. gordonii and F. nucleatum: , encoding a tyrosine kinase, and , encoding an internalin family surface protein. Ptk1, but not InlJ, is required for community development with S. gordonii, and we found that the action of this kinase is similarly required for P. gingivalis to accumulate in a community with F. nucleatum. A limited number of P. gingivalis genes are therefore required for species-independent synergy, and the Ptk1 tyrosine kinase network may integrate and coordinate input from multiple organisms.

摘要

许多病原微生物生态系统是多微生物的,群落功能可以通过细菌间的相互作用来塑造。然而,对于在异质群落环境中适应所需的遗传决定因素,人们知之甚少。在牙周病中,牙龈卟啉单胞菌是主要病原体,但仅存在于多微生物群落中。在这里,我们使用牙龈卟啉单胞菌的转座子测序 (Tn-Seq) 文库筛选影响该生物体在与口腔共生种链球菌和核梭杆菌共感染鼠脓肿模型中适应性的基因。影响与任何一种生物体适应性的基因涉及多种过程,包括代谢和能量产生,以及细胞壁和膜生物发生。尽管功能总体相似,但大多数鉴定出的基因都与伙伴物种特异性相关,表明牙龈卟啉单胞菌协同作用机制在很大程度上根据群落组成而有所不同。只有两个基因被确定为牙龈卟啉单胞菌在与链球菌和核梭杆菌共感染脓肿发展中适应所必需的:编码酪氨酸激酶的和编码内毒素家族表面蛋白的。Ptk1,但不是 InlJ,是与链球菌共同发育所必需的,我们发现这种激酶的作用同样需要与核梭杆菌共同发育才能在群落中积累。因此,牙龈卟啉单胞菌只需要少数几个基因即可实现种间协同作用,而 Ptk1 酪氨酸激酶网络可能整合并协调来自多种生物体的输入。

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