Living dangerously: Burkholderia pseudomallei modulates phagocyte cell death to survive

Abstract

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a major cause of sepsis and mortality in endemic regions of Southeast Asia and Northern Australia. As a facultative intracellular pathogen, B. pseudomallei produces virulence factors to evade innate host response and survive within host cells. Neutrophils and macrophages are phagocytes that play critical roles in host defense against pathogens by their ability to detect and eliminate microbes. Host defense processes against B. pseudomallei including phagocytosis, oxidative burst, autophagy, apoptosis, and proinflammatory cytokine release are all initiated by these two phagocytes in the fight against this bacterium. In vitro studies with mouse macrophage cell lines revealed multiple evasion strategies used by B. pseudomallei to counteract these innate processes. B. pseudomallei invades and replicates in neutrophils but little is known regarding its evasion mechanisms. The bidirectional interaction of neutrophils and macrophages in controlling B. pseudomallei infection has also been overlooked. Here the hypothesis that B. pseudomallei hijacks neutrophils and uses them to transport and infect new phagocytes is proposed as an evasion strategy to survive and persist in host phagocytes. This two-pronged approach by B. pseudomallei to replicate in two different types of phagocytes and to modulate their cell death modes is effective in promoting persistence and survival of the bacterium.