Exploring the HME and HAE1 efflux systems in the genus Burkholderia

Abstract

<p>Abstract</p> <p>Background</p> <p>The genus <it>Burkholderia </it>includes a variety of species with opportunistic human pathogenic strains, whose increasing global resistance to antibiotics has become a public health problem. In this context a major role could be played by multidrug efflux pumps belonging to Resistance Nodulation Cell-Division (RND) family, which allow bacterial cells to extrude a wide range of different substrates, including antibiotics. This study aims to i) identify <it>rnd </it>genes in the 21 available completely sequenced <it>Burkholderia </it>genomes, ii) analyze their phylogenetic distribution, iii) define the putative function(s) that RND proteins perform within the <it>Burkholderia </it>genus and iv) try tracing the evolutionary history of some of these genes in <it>Burkholderia</it>.</p> <p>Results</p> <p>BLAST analysis of the 21 <it>Burkholderia </it>sequenced genomes, using experimentally characterized <it>ceoB </it>sequence (one of the RND family counterpart in the genus <it>Burkholderia</it>) as probe, allowed the assembly of a dataset comprising 254 putative RND proteins. An extensive phylogenetic analysis revealed the occurrence of several independent events of gene loss and duplication across the different lineages of the genus <it>Burkholderia</it>, leading to notable differences in the number of paralogs between different genomes. A putative substrate [antibiotics (HAE1 proteins)/heavy-metal (HME proteins)] was also assigned to the majority of these proteins. No correlation was found between the ecological niche and the lifestyle of <it>Burkholderia </it>strains and the number/type of efflux pumps they possessed, while a relation can be found with genome size and taxonomy. Remarkably, we observed that only HAE1 proteins are mainly responsible for the different number of proteins observed in strains of the same species. Data concerning both the distribution and the phylogenetic analysis of the HAE1 and HME in the <it>Burkholderia </it>genus allowed depicting a likely evolutionary model accounting for the evolution and spreading of HME and HAE1 systems in the <it>Burkholderia </it>genus.</p> <p>Conclusion</p> <p>A complete knowledge of the presence and distribution of RND proteins in <it>Burkholderia </it>species was obtained and an evolutionary model was depicted. Data presented in this work may serve as a basis for future experimental tests, focused especially on HAE1 proteins, aimed at the identification of novel targets in antimicrobial therapy against <it>Burkholderia </it>species.</p