Comparative "-omics" in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors.
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.
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.
Maria
M
Lluch-Senar
Bioinformatics Unit, Centre for Genomic Regulation (CRG) and UPF, Dr. Aiguader 88, Barcelona, Spain.
Luca
L
Cozzuto
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.
Jaime
J
Cano
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.
Javier
J
Delgado
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.
Verónica
V
Llórens-Rico
Univ. Bordeaux, INRA, USC-EA3671 Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France; Bacteriology department, Bordeaux University Hospital, Bordeaux, France.
Sabine
S
Pereyre
Univ. Bordeaux, INRA, USC-EA3671 Mycoplasmal and Chlamydial Infections in Humans, Bordeaux, France; Bacteriology department, Bordeaux University Hospital, Bordeaux, France.
Cécile
C
Bebear
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; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, Barcelona, Spain.
Luis
L
Serrano
D018829:Adhesins, Bacterial / Q000235:genetics; D000940:Antigenic Variation / Q000235:genetics; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D005060:Europe / Q000453:epidemiology; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D054643:INDEL Mutation; D007564:Japan / Q000453:epidemiology; D008969:Molecular Sequence Data; D009154:Mutation; D009177:Mycoplasma pneumoniae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D016366:Open Reading Frames; D011019:Pneumonia, Mycoplasma / Q000453:epidemiology / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D020543:Proteome; D059467:Transcriptome; D014416:Tunisia / Q000453:epidemiology; D014774:Virulence / Q000235:genetics
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C546120:CARDS toxin, Mycoplasma pneumoniae; D020543:Proteome; C035471:adhesin, Mycoplasma pneumoniae