Evolution of a Pathogen: A Comparative Genomics Analysis Identifies a Genetic Pathway to Pathogenesis in <em>Acinetobacter</em>

<div><p><em>Acinetobacter baumannii</em> is an emergent and global nosocomial pathogen. In addition to <em>A. baumannii</em>, other <em>Acinetobacter</em> species, especially those in the <em>Acinetobacter calcoaceticus</em>-<em>baumannii</em> (<em>Acb</em>) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in <em>A. baumannii</em> have been identified, the genetic mechanisms that explain the emergence of <em>A. baumannii</em> as the most widespread and virulent <em>Acinetobacter</em> species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus <em>Acinetobacter</em>. However, a global comparison of genomic features between <em>Acinetobacter</em> spp. has not been described in the literature. In this study, 136 <em>Acinetobacter</em> genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the <em>Acinetobacter</em> genus. A whole genome phylogeny confirmed that <em>A. baumannii</em> is a monophyletic clade and that the larger <em>Acb</em> complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of <em>A. baumannii</em>. In addition, several genes associated with <em>A. baumannii</em> pathogenesis were found to be more conserved in the <em>Acb</em> complex, and especially in <em>A. baumannii</em>, than in other <em>Acinetobacter</em> genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of <em>A. baumannii</em>. The identification of novel features associated with transcriptional regulation and acquired by clades in the <em>Acb</em> complex presents targets for better understanding the evolution of pathogenesis and virulence in the expansion of the genus.</p>