Bactericidal Properties of Group IIA and Group V Phospholipases A2

Abstract

Group V phospholipase A2 (PLA2) is a recently characterized 14-kDa secretory PLA2 of mammalian heart and macrophage-derived cells. Group IIA PLA2, which is structurally close to group V PLA2, has been shown to kill Gram-positive bacteria in vitro and to prevent symptoms of Gram-positive infection in vivo. We studied the antibacterial properties of fully active recombinant rat group IIA and V PLA2s. Both group IIA and V PLA2s were highly bactericidal against Gram-positive bacteria, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Only high concentrations of group IIA PLA2 showed some bactericidal effect against the Gram-negative bacterium Escherichia coli. Our results confirm that group IIA PLA2 is a potent antibacterial enzyme against Gram-positive bacteria. Moreover, we show here that group V PLA2 is a novel antibacterial mammalian protein, but is less potent than group IIA PLA2. Both enzymes may be considered as future therapeutic agents against bacterial infections.

Lysis of Human Immunodeficiency Virus Type 1 by a Specific Secreted Human Phospholipase A2

“…The antibacterial effects of sPLA 2 s against gram-positive bacteria (ranked in order of strength, from highest to lowest, as follows: IIA, X, V, XII, IIE, IB and IIF) and the gram-negative bacterium Escherichia coli have been reported previously; only human group XII displays detectable bactericidal rather than bacteriostatic activity (7,11,12,26). In this study, group X alone exerted an antiviral effect on enveloped lentiviruses, documenting the specificity of this effect.…”

“…sPLA 2 -X is converted from a catalytically inactive zymogen to a mature, catalytically active form by removal of the N-terminal propeptide after the secretion process, supporting the extracellular action of this enzyme (14). Some sPLA 2 s have bactericidal activity, presumably through their effect on membrane integrity, raising the possibility that they may contribute to host antimicrobial defense (7,11,12,26). On the other hand, the role of sPLA 2 s in viral infections has not been defined.…”

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

“…Moreover, host cells up-regulate their lysosomal phospholipase A activity following mycobacterial infection (27). This may hint toward a bactericidal activity of this enzyme as shown for other phospholipase A 2 types (28). It may also be a direct response to the increased amount of phospholipids in the phagosome, facilitating degradation of cardiolipin, and release of lysocardiolipin.…”

Multiple Roles of Phospholipase A2during Lung Infection and Inflammation

“…In addition to the numerous contributions toward the enhancement of the inflammatory response attributable to sPLA 2 s, several isoforms exert an innate defensive role by virtue of their inherent bactericidal activity (15). Gram-positive organisms, such Listeria monocytogenes, Staphylococcus aureus, and Bacillus anthracis, appear to be directly susceptible to sPLA 2 activity both in vitro and in vivo owing to the ability of sPLA 2 to hydrolyze bacterial-membrane phospholipids (36,41,42,61,96). Interestingly, lethal factor produced by B. anthracis is capable of down-regulating sPLA 2 group IIA expression by alveolar macrophages, a potential virulence mechanism utilized by anthrax to protect itself from destruction by host defenses (36).…”