Infection and Cancer Laboratory, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
Bioinformatics Research Laboratory, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
Sci Rep. 2020 Jun 11;10(1):9505. doi: 10.1038/s41598-020-66194-4.
To assess the role of core metabolism genes in bacterial virulence - independently of their effect on growth - we correlated the genome, the transcriptome and the pathogenicity in flies and mice of 30 fully sequenced Pseudomonas strains. Gene presence correlates robustly with pathogenicity differences among all Pseudomonas species, but not among the P. aeruginosa strains. However, gene expression differences are evident between highly and lowly pathogenic P. aeruginosa strains in multiple virulence factors and a few metabolism genes. Moreover, 16.5%, a noticeable fraction of the core metabolism genes of P. aeruginosa strain PA14 (compared to 8.5% of the non-metabolic genes tested), appear necessary for full virulence when mutated. Most of these virulence-defective core metabolism mutants are compromised in at least one key virulence mechanism independently of auxotrophy. A pathway level analysis of PA14 core metabolism, uncovers beta-oxidation and the biosynthesis of amino-acids, succinate, citramalate, and chorismate to be important for full virulence. Strikingly, the relative expression among P. aeruginosa strains of genes belonging in these metabolic pathways is indicative of their pathogenicity. Thus, P. aeruginosa strain-to-strain virulence variation, remains largely obscure at the genome level, but can be dissected at the pathway level via functional transcriptomics of core metabolism.
为了评估核心代谢基因在细菌毒力中的作用——不考虑它们对生长的影响——我们对 30 株完全测序的假单胞菌的基因组、转录组和在果蝇和小鼠中的致病性进行了相关性分析。基因的存在与所有假单胞菌物种的致病性差异密切相关，但与铜绿假单胞菌菌株无关。然而，在多种毒力因子和少数代谢基因中，高致病性和低致病性铜绿假单胞菌菌株之间的基因表达差异明显。此外，16.5%，即铜绿假单胞菌菌株 PA14 的核心代谢基因的一个显著部分（与测试的非代谢基因的 8.5%相比），在突变时似乎对完全毒力是必需的。这些丧失毒力的核心代谢突变体中的大多数，在不依赖于营养缺陷的情况下，在至少一个关键的毒力机制中受到损害。PA14 核心代谢的通路水平分析表明，β-氧化和氨基酸、琥珀酸、柠檬酸和色氨酸的生物合成对完全毒力很重要。引人注目的是，这些代谢途径中基因在铜绿假单胞菌菌株之间的相对表达表明了它们的致病性。因此，铜绿假单胞菌菌株间的毒力变异在基因组水平上仍然很大程度上不明确，但可以通过核心代谢的功能转录组学在通路水平上进行剖析。
