Acinetobacter baumannii is a nosocomial pathogen that exhibits substantial genomic plasticity. Here, the identification of two variants of A. baumannii ATCC 17978 that differ based on the presence of a 44 kb accessory locus, which was named AbaAL44 (“ A. baumannii accessory locus 44 kb”), is described. Analyses of existing deposited data suggest that both variants are found in published studies of A. baumannii ATCC 17978 and that ATCC-derived laboratory stocks are comprised of a mix of these two variants. Yet, each variant exhibits distinct interactions with the host in vitro and in vivo . Infection with the variant that harbors AbaAL44 ( Ab 17978 UN) results in decreased bacterial burdens and increased neutrophilic lung inflammation in a mouse model of pneumonia, and affects the production of IL-1β and IL-10 by infected macrophages. AbaAL44 harbors putative pathogenesis genes including those predicted to encode for a type I pilus cluster, a catalase, and a cardiolipin synthase. The accessory catalase increases A. baumannii resistance to oxidative stress and neutrophil-mediated killing in vitro . The accessory cardiolipin synthase plays a dichotomous role by promoting bacterial uptake and increasing IL-1β production by macrophages, but also enhancing bacterial resistance to cell envelope stress. Collectively, these findings highlight the phenotypic consequences of A. baumannii’s genomic dynamism through the evolution of two variants of a common type strain with distinct infection-related attributes.

Pathogenic Acinetobacter species, most notably Acinetobacter baumannii, are a significant cause of healthcare‐associated infections worldwide. Acinetobacter infections are of particular concern to global health due to the high rates of multidrug resistance and extensive drug resistance. Widespread genome sequencing and analysis has determined that bacterial antibiotic resistance is often acquired and disseminated through the movement of mobile genetic elements, including insertion sequences (IS), transposons, integrons, and conjugative plasmids. In Acinetobacter specifically, resistance to carbapenems and cephalosporins is highly correlated with IS, as many ISAba elements encode strong outwardly facing promoters that are required for sufficient expression of β‐lactamases to confer clinical resistance. Here, we review the role of mobile genetic elements in antibiotic resistance in Acinetobacter species through the framework of the mechanism of resistance acquisition and with a focus on experimentally validated mechanisms.