Type IIA Secreted Phospholipase A2 in Host Defense against Bacterial Infections

sPLA2-IIA is an endogenous antimicrobial protein produced by many tissues and host cells, and displays high constitutive expression at barrier sites and inducible expression in the circulation. sPLA2-IIA is unique in its particular selectivity and potency in killing Gram-positive bacteria; it plays an underappreciated role in defense against Gram-negative pathogens. Bacteria can interfere with sPLA2-IIA-mediated killing through manipulation of its expression or through cell-envelope modifications and effective repair mechanisms. On mucosal surfaces, sPLA2-IIA expression impacts on the composition of the microbiome. sPLA2-IIA could be used as a stand-alone therapeutic agent, or as an adjunct therapy to existing antibiotics, to treat infections caused by antibiotic-resistant bacteria. The enzyme type IIA secreted phospholipase A2 (sPLA2-IIA) is crucial for mammalian innate host defense against bacterial pathogens. Most studies have investigated the role of sPLA2-IIA in systemic bacterial infections, identifying molecular pathways of bacterial resistance against sPLA2-IIA-mediated killing, and providing insight into sPLA2-IIA mechanisms of action. Sensitization of (antibiotic-resistant) bacteria to sPLA2-IIA action by blocking bacterial resistance or by applying sPLA2-IIA to treat bacterial infections might represent a therapeutic option in the future. Because sPLA2-IIA is highly expressed at mucosal barriers, we also discuss how sPLA2-IIA is likely to be an important driver of microbiome composition; we anticipate that future research in this area may bring new insights into the role of sPLA2-IIA in health and disease. The enzyme type IIA secreted phospholipase A2 (sPLA2-IIA) is crucial for mammalian innate host defense against bacterial pathogens. Most studies have investigated the role of sPLA2-IIA in systemic bacterial infections, identifying molecular pathways of bacterial resistance against sPLA2-IIA-mediated killing, and providing insight into sPLA2-IIA mechanisms of action. Sensitization of (antibiotic-resistant) bacteria to sPLA2-IIA action by blocking bacterial resistance or by applying sPLA2-IIA to treat bacterial infections might represent a therapeutic option in the future. Because sPLA2-IIA is highly expressed at mucosal barriers, we also discuss how sPLA2-IIA is likely to be an important driver of microbiome composition; we anticipate that future research in this area may bring new insights into the role of sPLA2-IIA in health and disease. occurs by antibiotic inactivation by bacteria, binding site modifications, or alterations of antibiotic accumulation through modification of bacterial permeability. a molecule stored in primary granules of neutrophils that is cytotoxic to Gram-negative bacteria by complex formation with lipopolysaccharide (LPS). an acute-phase protein found in blood plasma. In healthy adults concentrations are low but rise in response to inflammation. In the clinic, CRP is used as an inflammation marker. components of the innate immune system, consisting of small proteins that circulate in the blood as inactive precursors. Activation of the complement system can occur through three pathways, resulting in bacterial opsonization, recruitment of phagocytes, and the formation of the MAC that kills Gram-negative bacteria through pore formation. an inherited disease caused by mutations in the transmembrane conductance regulator (CFTR). CF is characterized by mucous dehydration resulting in obstructions of tracts such as the digestive and respiratory systems. Bacterial airway infections are a major problem in CF. microbial imbalance inside the body, such as impaired microbiota composition. a classification of bacteria based on the color staining procedure developed by Gram. host innate response to infection or harmful stimulation characterized by redness, swelling, heat, pain, and organ dysfunction. lipid microdomains within plasma membranes. They serve to compartmentalize cellular processes and promote kinetically favorable interactions that are necessary for signal transduction. bacterial proteins that carry an LPXTG amino acid motif through which they are covalently anchored to cell wall peptidoglycan. a lytic pore consisting of multiple complement proteins; forms in bacterial target membranes. conserved structures in pathogens such as LPS and peptidoglycan that are recognized by host specific receptors such as TLRs. a characteristic component of the bacterial cell wall. Consists of a mesh-like network of sugars and amino acids. a superfamily of enzymes that hydrolyze phospholipids in both eukaryotic and prokaryotic cell membranes. cell wall glycopolymers of Gram-positive bacteria. TAs are classified as lipoteichoic acids or wall teichoic acids depending on anchoring to the membrane or PG, respectively. a family of evolutionary conserved innate receptors that specifically recognize microbial molecules. also known as pancreatic sPLA2, an enzyme that is mostly involved in food digestion. the only sPLA2 family member with high bactericidal activity, predominantly against Gram-positive bacteria. a needle-like structure used by bacteria to inject toxins into eukaryotic cell.