clearance, as these bacteria are known to escape from phagosomal/endosomal compartments within 1520 minutes of uptake. Bacteria opsonized in 1% NHS elicited a greatly reduced ROS response, which corresponds to the inefficient clearance observed for these bacteria. Interestingly, bacteria opsonized with 20% NHS elicited similar ROS levels as bacteria opsonized in 5% and 10% NHS, however the 20% opsonized bacteria were cleared at a significantly higher rate than the 510% opsonized bacteria. This suggests that other neutrophil-related mechanisms besides the respiratory burst may become activated in response to these higher levels of C3 deposition and contribute to killing of these Burkholderia 
species B. pseudomallei are susceptible to the bactericidal action of certain antimicrobial peptides that are produced by neutrophils, specifically the cathelicidin peptide, LL37. In addition, neutrophils contain a wide variety of antimicrobial molecules including additional antimicrobial peptides or defensins, myeloperoxidase, neutrophil extracellular traps, and serine proteases which could work in concert with ROS generation. NETs were recently demonstrated to be antibacterial against B. pseudomallei, and NET release in response to B. pseudomallei was NADPH-oxidase dependent, as has been demonstrated previously with other agonists. Since those studies were performed with Digitoxin site unopsonized B. pseudomallei, our findings indicate that NET release may occur at a much faster rate with serum-opsonized bacteria in coordination with the rapid induction of the respiratory burst. Altogether, our data demonstrate 20581845 a clear requirement for complement opsonization to allow for efficient uptake 19791803 and killing of B. pseudomallei by neutrophils, and this bacterial clearance is dependent on achieving a rapid respiratory burst that elicits a threshold level of ROS generation. Although melioidosis could historically be considered a neglected tropical disease, the global interest in these infections has increased dramatically in the past decade. The regions where B. pseudomallei has been recovered from soils has expanded beyond southeast Asia and northern Australia, and now includes large areas of the Middle East and South/Central America ]. Concurrently, an increase in melioidosis cases has been observed in many of these regions. Diabetes is a major risk factor for acquiring these infections, as well as for developing severe disease. Because diabetes rates are rapidly increasing worldwide, it is likely that the number of melioidosis cases will also rise substantially. Together with the reports that B. pseudomallei possesses virulence attributes that make it attractive for misuse in bioterrorism-related releases has generated great interest in better understanding how this pathogen can so efficiently evade our immune defenses. Neutrophils have recently been reported to be prominently associated with B. pseudomallei infections in vivo and possess many qualities that would suggest they are capable of promoting host clearance. However, the previous in vitro studies have reported disparate findings as to abilities of neutrophils to control these infections. While our findings strongly indicate that neutrophils can efficiently clear B. pseudomallei, these activities appear to be dependent on the presence of critical C3 levels deposited on the surface of this pathogen. Thus, the differences observed between our findings and those of some previous publications may be partly attributed
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