Lluch-Senar Maria, Cozzuto Luca, Cano Jaime, Delgado Javier, Llórens-Rico Verónica, Pereyre Sabine, Bebear Cécile, Serrano Luis
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, Barcelona, Spain.
Bioinformatics Unit, Centre for Genomic Regulation (CRG) and UPF, Dr. Aiguader 88, Barcelona, Spain.
PLoS One. 2015 Sep 3;10(9):e0137354. doi: 10.1371/journal.pone.0137354. eCollection 2015.
The human respiratory tract pathogen M. pneumoniae is one of the best characterized minimal bacterium. Until now, two main groups of clinical isolates of this bacterium have been described (types 1 and 2), differing in the sequence of the P1 adhesin gene. Here, we have sequenced the genomes of 23 clinical isolates of M. pneumoniae. Studying SNPs, non-synonymous mutations, indels and genome rearrangements of these 23 strains and 4 previously sequenced ones, has revealed new subclasses in the two main groups, some of them being associated with the country of isolation. Integrative analysis of in vitro gene essentiality and mutation rates enabled the identification of several putative virulence factors and antigenic proteins; revealing recombination machinery, glycerol metabolism and peroxide production as possible factors in the genetics and physiology of these pathogenic strains. Additionally, the transcriptomes and proteomes of two representative strains, one from each of the two main groups, have been characterized to evaluate the impact of mutations on RNA and proteins levels. This study has revealed that type 2 strains show higher expression levels of CARDS toxin, a protein recently shown to be one of the major factors of inflammation. Thus, we propose that type 2 strains could be more toxigenic than type 1 strains of M. pneumoniae.
人类呼吸道病原体肺炎支原体是特征最为明确的最小细菌之一。到目前为止，已描述了该细菌的两类主要临床分离株（1型和2型），它们的P1黏附素基因序列不同。在此，我们对23株肺炎支原体临床分离株的基因组进行了测序。研究这23株菌株以及之前测序的4株菌株的单核苷酸多态性、非同义突变、插入缺失和基因组重排，发现了两个主要组中的新亚类，其中一些与分离国家有关。对体外基因必需性和突变率的综合分析使得能够鉴定出几种假定的毒力因子和抗原蛋白；揭示了重组机制、甘油代谢和过氧化物产生可能是这些致病菌株遗传和生理学中的因素。此外，对来自两个主要组各一株的两个代表性菌株的转录组和蛋白质组进行了表征，以评估突变对RNA和蛋白质水平的影响。这项研究表明，2型菌株显示出较高水平的CARDS毒素表达，最近发现该蛋白是炎症的主要因素之一。因此，我们认为2型菌株可能比1型肺炎支原体菌株更具毒性。
