Mycoplasma pneumoniaes perspectives in systems and synthetic biology

aPompeu Fabra University (UPF) bCenter for Genomic Regulation (CRG)

Jaime Cano Martnez-Botasa,b

This project has pictured an overview of the most recent advances of the systems and synthetic biology fields in relation to the smallbacterium M. pneumoniae and the final goal of achieving the minimal cell and the chassis cell. In this context the unpublished pathogenesisstudy stands as another step forward in the direction of a better understanding the bacterium. It has allowed the identification of all SNPs,missense, indels and rearrangements in the genome of different M. pneumoniae strains refining the typing and revealing sub-classes in thetwo main groups. This new data will allow for further studies to search specifically for those differences between strains and their effect inpathogenesis and response to antibiotics and immune system. The study as a whole revealed one of this differences, that a single mutationin the mpn372 gene increases the levels of CARDs toxin in Type II strains, a protein that induces a strong immune response, this leads tothe conclusion that Type II strains should be more virulent that Type I strains. Further work with this genome reduced bacterium is requiredfor addressing these final objectives.

Conclusion:

References:1. Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev. 2004 Oct;17(4):6977282. Maniloff J, McElhaney RN, Finch LR, Baseman JB (Editors). Mycoplasmas: molecular biology and pathogenesis. American Society for Microbiology; 1992

3. Xavier JC, Patil KR, Rocha I. Systems biology perspectives on minimal and simpler cells. Microbiol Mol Biol Rev . 2014 Sep 1;78(3):487509.

Mycoplasma pneumoniae was initially described in the 1940s as a highly pathogenic organism. Since then it has become recognized as ahuman lung pathogen which produces primary atypical pneumonia, among other extrapulmonary complications. Moreover, it stands as oneof the smallest and best characterized bacteria, known by its reduced genome and lack of cell wall. There is a classification with two mainsubgroups or clinical isolates of this bacteria, types I and II, which appear to switch predominance in specific geographical areas throughtime. Nowadays, M. pneumoniae, thanks to its reduced genome, stands as an ideal candidate for achieving both goals of minimal cell andchassis cell within systems and synthetic biology. For these purposes it is necessary the identification of those genetic features associatedwith pathogenicity within the bacteria. Here we study 22 sequenced clinical isolates of M. pneumoniae through the analysis of SNPs,missense, indels and genome rearrangements. They revealed a new classification of strains and higher levels of CARDs toxin in Type IIstrains which may indicate increased virulence and pathogenicity in this group.

Abstract:

It is a 800kb genomereduced bacterium with an

absent cell wall.

Its clinical isolate classification iscarried out by comparing only a

few genes and intergenic regions.

Mycoplasma pneumoniaeIt is responsible for 15-20% of all community-acquired

pneumonias

Leaving unclear what other genomic differences exist, which possibly affect pathogenesis and

antibiotic response.