Mpn491, a secreted nuclease ofMycoplasma pneumoniae, plays a critical role in evading killing by neutrophil extracellular traps

Abstract

Neutrophils play an important role in antimicrobial defense as the first line of innate immune system. Recently, the release of neutrophil extracellular traps (NETs) has been identified as a killing mechanism of neutrophils against invading microbes. Mycoplasma pneumoniae, a causative agent of respiratory infection, has been shown to be resistant to in vitro killing by neutrophils, suggesting that the bacterium might circumvent bactericidal activity of NETs. In this study, we investigated whether M. pneumoniae possesses resistance mechanisms against the NETs-mediated killing of neutrophils and found that the bacterium degrades the NETs induced upon M. pneumoniae infection. The NETs-degrading ability of M. pneumoniae required the production of a secreted nuclease, Mpn491, capable of using Mg as a cofactor for its hydrolytic activity. Moreover, the inactivation of the nuclease resulted in increased susceptibility of M. pneumoniae to the NETs-mediated killing of neutrophils. The results suggest that M. pneumoniae employs Mpn491 as a means for evading the killing mechanism of neutrophils.

High Mycoplasma pneumoniae Loads and Persistent Long-term Mycoplasma pneumoniae DNA in Lower Airway Associated with Severity of Pediatric Mycoplasma pneumoniae Pneumonia

“…Airway hypersecretion, epithelial desquamation, and remodeling cause AO, which compromises further clearance in vitro [7] , which was consistent with our present study. Other studies have shown that MP is resistant to killing by neutrophils, suggesting that the bacterium might circumvent bactericidal activity of neutrophil extracellular traps [14] . B cells and MP-specific antibodies are also crucial for its clearance in the lungs of mice [15] .…”

Interactions of Mycoplasma hyopneumoniae with extracellular traps

“…S. pneumoniae, Staphylococcus aureus, M. pneumoniae and other upper respiratory tract pathogens have exhibited nuclease activity in which there is a higher rate of bacterial survival when the nucleases are employed (7,58). The complete extent of nuclease utilization by these pathogens is not greatly understood, however, the nuclease proves to be beneficial in deconstructing an immune defense mounted against the pathogens, aiding in their survival.…”

“…Mycoplasma pneumoniae, a human pathogen, is able to evade NET-mediated killing by degrading extracellular traps via a secreted nuclease (7). The conditional release of NETs and their direct role in the innate immune system is still to be fully understood, but several studies indicate that NETs are seen in infections with pathogens that are either too large to be phagocytized (i.e., fungal hyphae, bacterial aggregates) or evade phagocytosis entirely (61).…”

“…Interestingly, numerous mycoplasmas exhibit survival mechanisms that allow them to resist neutrophil phagocytosis (62), including M. pneumoniae (7). A study by Yamamoto et al…”

“…Lanes: 1, NEB 2-Log DNA Ladder; 2, 6 mM EDTA; 3, 6 mM EGTA; 4, 6 mM EDTA and 6 mM EGTA; 5, RPMI-1640; 6, PCR product control. other Mycoplasma spp., have exhibited cell surface nucleases (7,9). These nucleases could aid Mycoplasma in avoiding elimination by ETs and provide a mechanism to acquire nucleic acid precursors in vivo.…”