Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, 501 S. Preston St., Louisville, KY, 40292, USA.
Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville, Louisville, KY, 40292, USA.
Sci Rep. 2024 Sep 27;14(1):22247. doi: 10.1038/s41598-024-72451-7.
Porphyromonas gingivalis is a Gram-negative, anaerobic oral pathobiont, an etiological agent of periodontitis and the most commonly studied periodontal bacterium. Multiple low passage clinical isolates were sequenced, and their genomes compared to several laboratory strains. Phylogenetic distances were mapped, a gene absence-presence matrix generated, and core (present in all genomes) and accessory (absent in one or more genomes) genes delineated. Subsequently, a second pangenome delineating the prevalence of inherently essential genes was generated. The prevalence of genes conditionally essential for surviving tobacco exposure, abscess formation and epithelial invasion was also determined, in addition to genes encoding key proteolytic enzymes containing putative signal peptides. While the absolutely essential pangenome was highly conserved, significant differences in the complete and conditionally essential pangenomes were apparent. Thus, genetic plasticity appears to lie primarily in gene sets facilitating adaptation to variant disease-related environments. Those genes that are highly pervasive in the P. gingivalis absolutely essential pangenome or are highly prevalent and essential for fitness in disease-relevant models, may represent particularly attractive therapeutic targets worthy of further investigation. As mutations in absolutely essential genes are expected to be lethal, the data provided herein should also facilitate improved planning for P. gingivalis gene mutation strategies.
牙龈卟啉单胞菌是一种革兰氏阴性、厌氧的口腔共生菌,是牙周炎的病因之一,也是研究最多的牙周细菌。对多个低传代的临床分离株进行了测序,并将其基因组与几个实验室菌株进行了比较。绘制了系统发育距离图,生成了基因存在-缺失矩阵,并划分了核心(存在于所有基因组中)和辅助(存在于一个或多个基因组中)基因。随后,生成了第二个泛基因组,用于描绘固有必需基因的流行程度。此外,还确定了在烟草暴露、脓肿形成和上皮细胞侵袭中生存所必需的条件必需基因的流行程度,以及编码含有假定信号肽的关键蛋白水解酶的基因。虽然绝对必需的泛基因组高度保守,但完整和条件必需的泛基因组之间存在明显差异。因此,遗传可塑性似乎主要在于有助于适应不同疾病相关环境的基因集。那些在牙龈卟啉单胞菌绝对必需泛基因组中高度普遍存在,或者在与疾病相关的模型中高度流行且对适应性至关重要的基因,可能代表特别有吸引力的治疗靶点,值得进一步研究。由于绝对必需基因的突变预计是致命的,因此本文提供的数据也应该有助于更好地规划牙龈卟啉单胞菌基因突变策略。