Human non-pancreatic secretory phospholipase A(2) (hnpsPLA(2)) is a group IIA phospholipase A(2) which plays an important role in the innate immune response. This enzyme was found to exhibit bactericidal activity toward Gram-positive bacteria, but not Gram-negative ones. Though native hnpsPLA(2) is active over a broad pH range, it is only highly active at alkaline conditions with the optimum activity pH of about 8.5. In order to make it highly active at neutral pH, we have obtained two hnpsPLA(2) mutants, Glu89Lys and Arg100Glu that work better at neutral pH in a previous study. In the present study, we tested the bactericidal effects of the native hnpsPLA(2) and the two mutants. Both native hnpsPLA(2) and the two mutants exhibit bactericidal activity toward Gram-positive bacteria. Furthermore, they can also kill Escherichia coil, a Gram-negative bacterium. The two mutants showed better bactericidal activity for E. coil at neutral pH than the native enzyme, which is consistent with the enzyme activities. As hnpsPLA(2) is highly stable and biocompatible, it may provide a promising therapy for bacteria infection treatment or other bactericidal applications. (C) 2013 Elsevier Inc. All rights reserved.