Burkholderia pseudomallei activates complement and is ingested but not killed by polymorphonuclear leukocytes

Area of Science:

• Immunology
• Microbiology
• Bacterial Pathogenesis

Background:

• Burkholderia pseudomallei is a Gram-negative bacterium causing melioidosis.
• The mechanisms of B. pseudomallei resistance to human serum lysis are not fully understood.
• Potential mechanisms include interference with complement activation, opsonization, or complement-mediated lysis.

Purpose of the Study:

• To investigate the interaction of B. pseudomallei with human complement.
• To determine the role of complement activation and opsonization in serum resistance.
• To elucidate the mechanisms underlying B. pseudomallei's resistance to complement-mediated lysis.

Main Methods:

• Studied complement activation by B. pseudomallei in vitro, with and without specific antibody.
• Assessed complement component deposition (C3b, iC3b, C5b-9) on bacterial surfaces.
• Investigated the role of opsonins in phagocytosis by polymorphonuclear leukocytes (PMNL).

Main Results:

• B. pseudomallei rapidly activated and consumed complement, primarily via the alternative pathway in the absence of antibody.
• Opsonically active C3b and iC3b fragments deposited on the bacterial surface.
• The membrane attack complex (C5b-9) deposited but was susceptible to elution, suggesting a non-microbicidal location.
• Opsonization enhanced PMNL phagocytosis and oxidative response, but significant bacterial killing was not observed.

Conclusions:

• B. pseudomallei activates complement, predominantly through the alternative pathway, leading to opsonin deposition.
• Serum resistance may stem from the membrane attack complex being deposited in a non-lytic manner.
• Despite enhanced phagocytosis and oxidative burst, B. pseudomallei exhibits resistance to killing by human PMNL.