Mycoplasma pneumoniae protects infected epithelial cells from hydrogen peroxide-induced cell detachment.

Epithelial cell shedding is a defense mechanism against infectious microbes that use these cells as an infection foothold, and that eliminates microbes from infection foci by removing infected cells. Mycoplasma pneumoniae, a causative agent of respiratory infections, is known to adhere to and colonize the surface of ciliated airway epithelial cells; it produces a large amount of hydrogen peroxide, indicating its capability of regulating hydrogen peroxide-induced infected cell detachment. In this study, we found that M. pneumoniae reduces exogenous hydrogen peroxide-induced detachment of the infected cells from culture plates. This cell detachment occurred dependently of DNA damage-initiated, poly (ADP-ribose) polymerase 1 (PARP1)-mediated cell death, or parthanatos. In cells infected with M. pneumoniae, exogenous hydrogen peroxide failed to induce DNA damage-initiated poly (ADP-ribose) (PAR) synthesis and concomitant increased cytoplasmic membrane rupture, both of which are biochemical hallmarks of parthanatos. The impairment of PAR synthesis was attributed to a reduction in the amount of cytosolic nicotinamide adenine dinucleotide (NAD), a substrate of PARP1, caused by M. pneumoniae. On the other hand, non-adherent mutant strains of M. pneumoniae showed a lower ability to reduce cell detachment than wild-type strains, but the extent to which NAD was decreased in infected cells was comparable to that seen in the wild-type strain. We found that NAD depletion could induce PARP1-independent cell detachment pathways following stimulation with hydrogen peroxide, and that M. pneumoniae could also regulate PARP1-independent cell detachment in a cytoadhesion-dependent manner. These results suggest that M. pneumoniae might regulate infected cell detachment induced by hydrogen peroxide that it produces itself, and such a mechanism may contribute to sustaining the bacterial infection.