Miller Daniel P, Scott David A
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA.
Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, KY, USA.
Trends Microbiol. 2021 Jan;29(1):54-64. doi: 10.1016/j.tim.2020.09.002. Epub 2020 Oct 15.
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
蛋白酶是牙龈卟啉单胞菌的关键毒力决定因素,牙龈卟啉单胞菌是一种新出现的与阿尔茨海默病、癌症和关节炎相关的病原体,也是已确定的牙周炎病原体。转座子测序已被用于确定该细菌的核心必需基因组以及在多种环境中条件必需的基因——脓肿形成、上皮定植和接触香烟烟雾毒素;还用于阐明铁获取和功能性9型分泌系统所需的基因。鉴定出的经过验证和预测的蛋白质分解代谢基因包括已确定的毒力因子和大量看似更普通的蛋白水解基因。研究了在多种与疾病相关的条件下具有必需性的基因的功能和相关性。这些与应激相关的共同基因可能是控制牙龈卟啉单胞菌感染特别有吸引力的治疗靶点。