Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability

Abstract

The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), have been reported to bind lipopolysaccharide (LPS), opsonize microorganisms, and enhance the clearance of lung pathogens. In this study, we examined the effect of SP-A and SP-D on the growth and viability of Gram-negative bacteria. The pulmonary clearance of Escherichia coli K12 was reduced in SP-A–null mice and was increased in SP-D–overexpressing mice, compared with strain-matched wild-type controls. Purified SP-A and SP-D inhibited bacterial synthetic functions of several, but not all, strains of E. coli, Klebsiella pneumoniae, and Enterobacter aerogenes. In general, rough E. coli strains were more susceptible than smooth strains, and collectin-mediated growth inhibition was partially blocked by coincubation with rough LPS vesicles. Although both SP-A and SP-D agglutinated E. coli K12 in a calcium-dependent manner, microbial growth inhibition was independent of bacterial aggregation. At least part of the antimicrobial activity of SP-A and SP-D was localized to their C-terminal domains using truncated recombinant proteins. Incubation of E. coli K12 with SP-A or SP-D increased bacterial permeability. Deletion of the E. coli OmpA gene from a collectin-resistant smooth E. coli strain enhanced SP-A and SP-D–mediated growth inhibition. These data indicate that SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane

Macrophage-independent Fungicidal Action of the Pulmonary Collectins

“…Several lines of evidence suggest that the collectins increase the permeability of the surface of Hc, as we have recently demonstrated for some but not all strains of Escherichia coli (8). Incubation of yeast with both collectins increased protein leak from the organism and enhanced the access of a hydrolysis-activated fluorescent substrate to intracellular alkaline phosphatase.…”

Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial‐associated lymphoid tissue

“…2,6 SP-D enhances the in vitro production of superoxide by alveolar macrophages 7 and inhibits T-lymphocyte proliferation. 8 In both in vitro and in vivo studies, SP-D has been reported to bind to, and mediate the clearance of, apoptotic inflammatory cells by alveolar macrophages.…”

Pulmonary Collectins Protect Macrophages against Pore-forming Activity of Legionella pneumophila and Suppress Its Intracellular Growth

“…We have shown previously that SP-A and SP-D regulate pulmonary inflammation through interaction with pattern recognition receptors, including Toll-like receptors, CD14 and MD-2 (8 -11). Pulmonary collectins also directly interact with microbes, including Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, and Mycoplasma pneumoniae, and inhibit their growth (12,13).…”