Domain-architecture aware phylogenetic profiling indicates a functional diversification of type IVa pili in the nosocomial pathogenAcinetobacter baumannii

Abstract

The Gram-negative bacterial pathogen Acinetobacter baumannii is a major cause of hospital-acquired opportunistic infections. The increasing spread of pan-drug resistant strains, paired with a surge in virulence, makes A. baumannii top-ranking among the ESKAPE pathogens for which novel routes of treatment are urgently needed. Comparative genomics approaches have successfully identified genetic changes that coincide with the emergence of pathogenicity in Acinetobacter. Genes that are prevalent both in pathogenic and a-pathogenic Acinetobacter species were not considered ignoring that virulence factors may emerge by the modification of evolutionarily old and widespread proteins. Here, we increased the resolution of comparative genomics analyses to also include lineage-specific changes in protein domain architectures. Using type IVa pili (T4aP) as an example, we show that two pilus components, FimU and the pilus tip adhesin ComC, exist with markedly differing domain architectures in pathogenic Acinetobacter species. ComC, has gained a von Willebrand Factor type A domain displaying a finger-like protrusion, and we provide experimental evidence that this finger conveys virulence-related functions in A. baumannii. Both genes together form an evolutionary cassette, which has been replaced at least twice during A. baumannii diversification. The resulting strain-specific differences in T4aP layout suggests differences in the way how individual strains interact with their host. Our study underpins the hypothesis that A. baumannii uses T4aP for host infection as it was shown previously for other pathogens. It also indicates that many more functional complexes may exist whose precise function can be rapidly adjusted by changing the domain architecture of individual proteins.

Physiological Roles of anAcinetobacter-specific σ Factor

“…were constructed similar to that previously described (65). Briefly, 2822 γ-proteobacteria genome assemblies were retrieved from the RefSeq database (release 213, downloaded on September 2022), selecting reference genomes and isolates of interest, including 196 isolates from the Acinetobacter genus.…”