Comparative “-omics” in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors

Abstract

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.

Diversity in Genotype Distribution of <i>Mycoplasma pneumoniae</i> Obtained from Children and Adults

“…The type-shift in dominant genotype from P1-1 to P1-2 was also found in our previous study (10). Type P1-1 and P1-2 strains in vitro formed biofilms that differ qualitatively and quantitatively, and P1-2 had a higher expression of community-acquired distress syndrome toxin that was a significant virulence factor specific to M. pneumoniae (11,12). Fan et al found that M. pneumoniae pneumonia (MPP) patients infected with P1-1 strains exhibited a higher risk of developing severe MPP (13).…”

Comparison of Mycoplasma pneumoniae Genome Sequences from Strains Isolated from Symptomatic and Asymptomatic Patients

“…These findings are concordant with those of Xiao et al In their analysis, the sequences of 15 M. pneumoniae strains seem very stable over time and at different locations in the world. Similarly, Lluch-Senar et al (2015) found a relatively low number of non-synonymous SNPs among the genome sequences of 23 strains from 6 different countries. However, they do report a high rate of variation among repetitive elements in the M. pneumoniae genomes (Lluch-Senar et al, 2015).…”

“…This sequence was derived from laboratory strain M129. Since 2013, several other genomic sequences have been published (Lluch-Senar et al, 2015; Simmons et al, 2013; Xiao et al, 2015). Most of these sequences were obtained in two independent studies.…”

“…One of these studies reported the comparative genome analysis of 15 M. pneumoniae strains isolated form respiratory tract samples and cerebrospinal fluid samples collected from patients between 1940 and 2009 in the USA, China, and England (Xiao et al, 2015). The other study reported the sequences of 23 clinical M. pneumoniae strains isolated between 1964 and 2011 in six different countries (Lluch-Senar et al, 2015). In both studies, the genomes of M. pneumoniae strains seem very stable over time and at different locations in the world.…”

“…In both studies, the genomes of M. pneumoniae strains seem very stable over time and at different locations in the world. The sequences of these studies show a low number of non-synonymous single-nucleotide polymorphisms, but a high rate of variation among repetitive elements (Lluch-Senar et al, 2015; Xiao et al, 2015). …”