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PMID: 12750409 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 111 ·No. 10 ·2003-05-00 ·Pages 1589-602

Wu H, Kuzmenko A, Wan S, Schaffer L, Weiss A, Fisher JH, Kim KS, McCormack FX

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.

MeSH Terms
Animals Bacterial Outer Membrane Proteins/genetics Bronchoalveolar Lavage Fluid/chemistry,microbiology Cell Division/drug effects Cell Membrane Permeability/drug effects Collectins/pharmacology Dactinomycin/pharmacokinetics Escherichia coli/drug effects,genetics,metabolism Escherichia coli Infections/drug therapy,metabolism Fluorescent Dyes/pharmacokinetics Genetic Predisposition to Disease Gram-Negative Bacteria/drug effects,genetics,metabolism Humans Mice Mice, Inbred C3H Mice, Knockout Microbial Sensitivity Tests Pulmonary Surfactant-Associated Protein A/deficiency,genetics,pharmacology Pulmonary Surfactant-Associated Protein D/biosynthesis,genetics,pharmacology Rats Rats, Sprague-Dawley Respiratory Tract Infections/drug therapy,metabolism
Chemicals
Bacterial Outer Membrane Proteins Collectins Fluorescent Dyes Pulmonary Surfactant-Associated Protein A Pulmonary Surfactant-Associated Protein D OMPA outer membrane proteins Dactinomycin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wu Huixing
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Kuzmenko Alexander
Wan Sijue
Schaffer Lyndsay
Weiss Alison
Fisher James H
Kim Kwang Sik
McCormack Francis X
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI16889
Published
2003-05-00
Pages
1589-602
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC155045
Subset
IM
Grants
NHLBI NIH HHS · HL-61612 · United States
NIEHS NIH HHS · P30ES-0609606 · United States
Corrections
CommentIn
PMID: 12750392
External Links
PubMed source DOI: 10.1172/JCI16889 PMC Full Text View journal details
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