Genomic analysis of Acinetobacter baumannii prophages reveals remarkable diversity and suggests profound impact on bacterial virulence and fitness

Ana Rita Costa,Rodrigo Monteiro,Joana Azeredo

doi:10.1038/s41598-018-33800-5

Ana Rita Costa, Rodrigo Monteiro + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-33800-5

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Journal: Scientific Reports	Publication Date: Oct 18, 2018
Citations: 54	License type: open-access

Affiliation: University of Minho

Abstract

The recent nomination by the World Health Organization of Acinetobacter baumannii as the number one priority pathogen for the development of new antibiotics is a direct consequence of its fast evolution of pathogenicity, and in particular of multidrug resistance. While the development of new antibiotics is critical, understanding the mechanisms behind the crescent bacterial antibiotic resistance is equally relevant. Often, resistance and other bacterial virulence elements are contained on highly mobile pieces of DNA that can easily spread to other bacteria. Prophages are one of the mediators of this form of gene transfer, and have been frequently found in bacterial genomes, often offering advantageous features to the host. Here we assess the contribution of prophages for the evolution of A. baumannii pathogenicity. We found prophages to be notably diverse and widely disseminated in A. baumannii genomes. Also remarkably, A. baumannii prophages encode for multiple putative virulence factors that may be implicated in the bacterium’s capacity to colonize host niches, evade the host immune system, subsist in unfavorable environments, and tolerate antibiotics. Overall our results point towards a significant contribution of prophages for the dissemination and evolution of pathogenicity in A. baumannii, and highlight their clinical relevance.

Highlights

Acinetobacter baumannii was recently indicated by the World Health Organization (WHO) as the number one priority pathogen for research and development of new antibiotics
When infecting a bacterial host, phages may follow distinct life cycles: virulent phages follow a lytic path in which they replicate inside the bacteria and cause cell lysis for progeny release; temperate phages may follow the lytic cycle or opt for a lysogenic cycle where they integrate into the host genome and replicate passively with the bacterial genome
To note that the analysis here performed included a large number of draft genomes (97.9%), which implies that PHAge Search Tool (PHAST) may under-estimate the number of intact prophages and over-estimate the number of defective prophages

Summary

Introduction

Acinetobacter baumannii was recently indicated by the World Health Organization (WHO) as the number one priority pathogen for research and development of new antibiotics (http://www.who.int/medicines/publications/ global-priority-list-antibiotic-resistant-bacteria/en/). We aimed at evaluating the prevalence of prophages in A. baumannii genomes, and at understanding the contribution of these elements to the rapid evolution of pathogenicity in this bacterial pathogen. The significantly higher prevalence of defective prophages (Fig. 1a) was expected since “intact prophages” are usually under strong selection by bacteria for mutations causing prophage inactivation[3].

Results

Conclusion