Abstract
Background Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium and a keystone pathogen in chronic periodontitis. Beyond oral disease, it has been implicated in systemic conditions, including cardiovascular disease, type 2 diabetes, rheumatoid arthritis, and neurodegeneration. Marked strain-to-strain differences in tissue invasion, immune evasion, and pathogenicity suggest that virulence is shaped by complex genetic and regulatory interactions rather than a single determinant. Objective To summarize current knowledge of the genetic diversity of P. gingivalis virulence determinants and their contribution to strain-specific pathogenicity. Design This narrative review synthesizes current evidence on the diversity of major virulence determinants, including fimbriae (FimA and Mfa1), gingipains (RgpA/RgpB/Kgp), Hag-family hemagglutinins, capsular polysaccharide loci, lipopolysaccharide variants, the RagAB nutrient acquisition system, and the type IX secretion system. It also examines the roles of allelic variation, domain rearrangements, phase variation, and horizontal gene transfer in shaping strain-specific virulence repertoires. Conclusions The reviewed evidence indicates that genetic variation across multiple virulence-associated loci contributes to substantial phenotypic diversity among P. gingivalis strains, influencing host interaction, tissue tropism, immune modulation, and pathogenic potential. Integrating comparative genomics with functional phenotyping provides a framework for predicting strain-specific virulence and may facilitate the development of improved diagnostic tools and targeted therapeutic strategies.
Hanie Ahmadi, J. Burks, Katherine A. Innamorati et al.· Journal of Oral Microbiology· 1 citation
ABSTRACT Haemophilus influenzae is a diverse human-restricted bacterium that normally colonizes the healthy nasopharynx but also causes common infections. Comparisons of clinical isolate genomes previously identified a gene, msf, that contained Sel1-like repeats that were associated with clinical disease. Mutant analysis had further found that msf improved survival in macrophages and increased systemic infection in an animal model. However, the role of msf in other conditions and its molecular function remain unknown. To identify protein-protein interactions with Msf, a yeast two-hybrid screen against an H. influenzae prey library was conducted, which found potential interactions with lipoprotein exporter protein LolD and an autotransporter adhesin Hap. To identify effects of msf on gene expression, we compared wild-type and mutant strains grown in multiple culture conditions by RNA-seq. The results indicate that msf modulates global gene expression in a condition-dependent manner, exerting an especially strong influence in starved surface-attached biofilm cells. The few consistent changes in mutants’ planktonic exponential and stationary phases included decreased expression of two paralogous autotransporter adhesins. By contrast, mutant cells in starved surface-attached biofilms had dramatic changes in expression, including upregulation of protein translation and downregulation of alternative carbon metabolism. However, assays of 24 hour biofilm phenotypes found only subtle gene expression changes. Together, the results point to a speculative model of Msf functioning as an envelope-associated chaperone whose presence affects the relative expression of proteins at the outer membrane. IMPORTANCE Comparing genomes from different clinical isolates of the same pathogenic bacterial species has identified genes associated with virulence, but many of these are understudied or have no known function. The msf gene was previously implicated as a virulence factor in Haemophilus influenzae, a common cause of mucosal diseases including middle-ear and chronic lung infections. This study finds that the msf gene causes condition-specific changes in gene expression, with especially dramatic changes in starved surface-attached biofilm cells. Along with identification of putative protein-protein interaction partners, the results provide new clues as to the molecular and cellular function of Msf, potentially as an envelope-associated chaperone involved in membrane protein trafficking. Understanding how virulence-associated genes like msf modulate bacterial responses to the environment may help explain why some bacterial strains remain harmless colonizers while others become pathogens. Comparing genomes from different clinical isolates of the same pathogenic bacterial species has identified genes associated with virulence, but many of these are understudied or have no known function. The msf gene was previously implicated as a virulence factor in Haemophilus influenzae, a common cause of mucosal diseases including middle-ear and chronic lung infections. This study finds that the msf gene causes condition-specific changes in gene expression, with especially dramatic changes in starved surface-attached biofilm cells. Along with identification of putative protein-protein interaction partners, the results provide new clues as to the molecular and cellular function of Msf, potentially as an envelope-associated chaperone involved in membrane protein trafficking. Understanding how virulence-associated genes like msf modulate bacterial responses to the environment may help explain why some bacterial strains remain harmless colonizers while others become pathogens.
Evangeline M Williams, Mary C. Marino, J. Hammond et al.· mBio· 0 citations
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