Pan genômica e análises de resistência e virulência sob seleção positiva darwiniana de Gardnerella vaginalis

Abstract

The Gardnerella genus comprises Gram-variable, anaerobic, hemolytic, and non motile bacilli. The main species of this genus is G. vaginalis, responsible for bacterial vaginosis (BV). Despite its importance, especially for women, and the availability of several strain genomes in public databases, genomic analysis and studies on effective treatments still lack detail. In this study, we set out to carry out bioinformatic analyses using 97 genomes of the species, mainly focusing on pan-genomics to investigate the complete set of genes and Darwinian positive selection to analyze which genes have been positively selected during evolution and have activities related to antimicrobial and virulence factors. Phylogenomics, combined with molecular epidemiology, provided greater resolution than wgMLST in identifying micro-events of evolution and clonal complexes of the species, genomic plasticity analysis aimed to identify events of acquisition and exclusion through horizontal gene transfer. The results revealed significant genome variability, indicating a highly diverse open pangenome. The low number of genes in the core genome and the heatmap similarity analysis confirmed this variability. Three pathogenicity islands, two resistance islands, and nine genomic islands were identified, showing horizontal gene transfer events. In addition, comparative genomic analyses identified resistance genes, such as Mef(A), related to macrolide resistance, and other genes, such as tet(M) and tet(L), related to tetracycline resistance. These genes were associated with Darwinian positive selection, indicating their importance in the adaptation and survival of the species. Two proteins were also selected as therapeutic targets through molecular modeling, such as WP_004132099.1 (sigA), which is a sigma factor of RNA polymerase necessary for the bacterial transcription process; and WP_004131683.1 (murB) is related to peptide-glycan formation in the prokaryotic cell wall. These findings emphasize the need to sequence new G. vaginalis genomes on a global scale to better understand this variability and the adaptation patterns of this species in its environment for developing effective treatments against bacterial vaginosis.