Lab. of Molecular and Microbial Evolution, Dep. of Evolutionary Biology, University of Florence, 50125 Firenze, Italy.
BMC Evol Biol. 2010 Jun 3;10:164. doi: 10.1186/1471-2148-10-164.
The genus Burkholderia 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 rnd genes in the 21 available completely sequenced Burkholderia genomes, ii) analyze their phylogenetic distribution, iii) define the putative function(s) that RND proteins perform within the Burkholderia genus and iv) try tracing the evolutionary history of some of these genes in Burkholderia.
BLAST analysis of the 21 Burkholderia sequenced genomes, using experimentally characterized ceoB sequence (one of the RND family counterpart in the genus Burkholderia) 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 Burkholderia, 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 Burkholderia 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 Burkholderia genus allowed depicting a likely evolutionary model accounting for the evolution and spreading of HME and HAE1 systems in the Burkholderia genus.
A complete knowledge of the presence and distribution of RND proteins in Burkholderia 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 Burkholderia species.
伯克霍尔德氏菌属包括多种具有机会致病性的人类菌株，其对抗生素的全球耐药性不断增强，已成为一个公共卫生问题。在这种情况下，耐药结节分裂（RND）家族的多药外排泵可能发挥重要作用，使细菌细胞能够排出多种不同的底物，包括抗生素。本研究旨在：i）鉴定 21 株完全测序的伯克霍尔德氏菌基因组中的 rnd 基因；ii）分析其系统发育分布；iii）确定 RND 蛋白在伯克霍尔德氏菌属中的潜在功能；iv）尝试追踪某些基因在伯克霍尔德氏菌中的进化历史。
使用实验确定的 ceoB 序列（伯克霍尔德氏菌属中 RND 家族的对应物之一）作为探针，对 21 株伯克霍尔德氏菌测序基因组进行 BLAST 分析，组装了一个包含 254 个推定 RND 蛋白的数据集。广泛的系统发育分析表明，在伯克霍尔德氏菌属的不同谱系中发生了多次基因丢失和复制的独立事件，导致不同基因组中旁系同源物的数量存在显著差异。还将推定的底物[抗生素（HAE1 蛋白）/重金属（HME 蛋白）]分配给这些蛋白中的大多数。在伯克霍尔德氏菌菌株的生态位和生活方式与其拥有的外排泵的数量/类型之间未发现相关性，而与基因组大小和分类学相关。值得注意的是，我们观察到，只有 HAE1 蛋白主要负责观察到相同物种菌株中不同数量的蛋白。关于 HAE1 和 HME 在伯克霍尔德氏菌属中的分布和系统发育分析的数据，描绘了一个可能的进化模型，该模型解释了 HME 和 HAE1 系统在伯克霍尔德氏菌属中的进化和传播。
获得了伯克霍尔德氏菌属中 RND 蛋白的存在和分布的完整知识，并描绘了一个进化模型。本工作中提供的数据可以作为未来实验测试的基础，特别是针对 HAE1 蛋白，旨在确定针对伯克霍尔德氏菌属物种的抗菌治疗的新靶标。
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