Comparative Genomic Analysis Reveals Genetic Mechanisms of the Variety of Pathogenicity, Antibiotic Resistance, and Environmental Adaptation of Providencia Genus

Abstract

The bacterial genus <i>Providencia</i> is Gram-negative opportunistic pathogens, which have been isolated from a variety of environments and organisms, ranging from humans to animals. <i>Providencia alcalifaciens</i>, <i>Providencia rettgeri</i>, and <i>Providencia stuartii</i> are the most common clinical isolates, however, these three species differ in their pathogenicity, antibiotic resistance and environmental adaptation. Genomes of 91 isolates of the genus <i>Providencia</i> were investigated to clarify their genetic diversity, focusing on virulence factors, antibiotic resistance genes, and environmental adaptation genes. Our study revealed an open pan-genome for the genus <i>Providencia</i> containing 14,720 gene families. Species of the genus <i>Providencia</i> exhibited different functional constraints, with the core genes, accessory genes, and unique genes. A maximum-likelihood phylogeny reconstructed with concatenated single-copy core genes classified all <i>Providencia</i> isolates into 11 distant groups. Comprehensive and systematic comparative genomic analyses revealed that specific distributions of virulence genes, which were highly homologous to virulence genes of the genus <i>Proteus</i>, contributed to diversity in pathogenicity of <i>Providencia alcalifaciens</i>, <i>Providencia rettgeri</i>, and <i>Providencia stuartii</i>. Furthermore, multidrug resistance (MDR) phenotypes of isolates of <i>Providencia rettgeri</i> and <i>Providencia stuartii</i> were predominantly due to resistance genes from class 1 and 2 integrons. In addition, <i>Providencia rettgeri</i> and <i>Providencia stuartii</i> harbored more genes related to material transport and energy metabolism, which conferred a stronger ability to adapt to diverse environments. Overall, our study provided valuable insights into the genetic diversity and functional features of the genus <i>Providencia</i>, and revealed genetic mechanisms underlying diversity in pathogenicity, antibiotic resistance and environmental adaptation of members of this genus.