Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance inAcinetobacter baumanniipopulations

Abstract

Public health organizations consider the multidrug resistant and opportunistic pathogen Acinetobacter baumannii , as a major global health concern. This species hosts multiple variants of AbaR-type genomic islands which carry several antibiotic resistance, including to carbapenems (AbaR4 variant). How these islands, conferring multidrug resistance, persist in A. baumannii populations remains elusive. Using complementary approaches, we investigated whether the manipulation of natural transformation by AbaRs, via their insertion strategy in the bacterial chromosome, might give them a selective advantage and contribute to the persistence of antibiotic resistance genes in A. baumannii populations. Natural transformation is a process through which bacteria can import and recombine exogenous DNA, facilitating gene transfer and allelic recombination. Although transformation promotes acquisition of mobile genetic elements (MGEs), it is also proposed to serve as a mechanism to purge them from the chromosome. Several MGEs inhibit transformation, suggesting that natural transformation can impede their evolutionary dynamics. We established an experimental model in which natural transformation spontaneously occurs in A. baumannii populations, allowing us to determine the rate of acquisition and removal of MGEs. We found that the majority of AbaRs disrupt the comM gene, causing differential inhibition of MGE acquisition, removal and allelic transfer events. A mathematical evolutionary model shows that AbaRs inserting into the comM gene gain a selective advantage over AbaRs whose insertion site either do not inhibit or completely inhibit transformation. The comM insertion strategy is advantageous when the model incorporates some degree of environmental complexity, such as combined antibiotic stress or changes in environmental resources. Our work highlights how AbaRs, and potentially other MGEs, can manipulate natural transformation to persist in populations, resulting in the high prevalence of multidrug resistance.