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

Abstract

AbstractThe opportunistic pathogenAcinetobacter baumannii, a major global public health concern, has developed multiple variants of AbaR-type genomic islands that confer multidrug resistance. The mechanisms facilitating the persistence of these potentially costly islands withinA. baumanniipopulations have remained enigmatic. In this study, we employed a combination of investigative methods to shed light on the factors contributing to their selective advantage and long-term persistence. The dissemination of AbaR islands is intricately linked to their horizontal transfer via natural transformation, a process through which bacteria can import and recombine exogenous DNA, facilitating allelic recombination, genetic acquisition, and deletion. In experimental populations, we first quantified the rate at which natural transformation events occur between individuals. Our findings indicate that the rate of AbaR deletion events is marginally higher than the rate of their acquisition. When this result is integrated into a model of population dynamics not exposed to antibiotic selection pressure, it leads to the swift removal of AbaRs from the population, a pattern that stands in contrast to AbaR prevalence in genomes. Yet, genomic analyses show that nearly all AbaRs-carryingA. baumanniihave at least one AbaR disruptingcomM, a gene encoding a helicase critical for natural transformation. We discovered that such disruption differentially inhibits the rate of genetic acquisition and deletion. Specifically, they significantly impede the removal of AbaRs while still enabling the host cell to acquire and recombine short sequences, such as allelic variants. Through mathematical evolutionary modeling, we demonstrate that AbaRs inserted intocomMgain a selective advantage over AbaRs inserted in sites that do not inhibit or completely inhibit transformation, in line with the genomic observations. The persistence of AbaRs within populations can be ascribed to their targeted integration into a gene, substantially diminishing the likelihood of their removal from the bacterial genome. In contrast, this integration enables the host cell to preserve the ability to acquire and eliminate various short heterologous sequences, enabling the host bacterium - and thus its AbaR - to adapt to the unpredictability of the environment and persist over the long term. This work underscores how AbaRs, and potentially other Mobile Genetic Elements (MGEs), can manipulate natural transformation to ensure their persistence in populations, ultimately leading to the high prevalence of multidrug resistance.