Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability
Open accessAbstract
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.
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Inactivation of alveolar surfactant decreases the elimination of surfactant-sensitive bacteria.
“The inactivation of alveolar surfactant decreases the elimination of surfactant-sensitive bacteria.”
From The microbiome and critical illness (2016) · cites this paper as [57]
In alveolar injury, the bactericidal surfactant layer is inactivated and microbial elimination is slowed by impairment of mucociliary clearance.
“The bactericidal surfactant layer is inactivated55,57 and microbial elimination is slowed by impairment of mucociliary clearance.”
From The microbiome and critical illness (2016) · cites this paper as [57]
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- Authors
- Wu, H., Kuzmenko, A., Wan, S., Schaffer, L., Weiss, A., Fisher, J. H., Kim, K. S., & McCormack, F. X.
- Affiliations
- University of Cincinnati (US)
- University of Colorado Denver (US)
- Johns Hopkins University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2003-05-15
- Volume
- 111
- Issue
- 10
- Pages
- 1589-1602
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC155045
- OpenAlex
- W2128714994
- Cited by
- 412
- References
- 68
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 12 · 2023: 8 · 2022: 13 · 2021: 25 · 2020: 19 · 2019: 15 · 2018: 14 · 2017: 18 · 2016: 12 · 2015: 24 · 2014: 12 · 2013: 15 · 2012: 21
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL61612, R01HL061612)
- National Institute of Environmental Health Sciences (P30ES-0609606)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- surfactant protein A, surfactant protein D, Gram-negative bacteria, bacterial growth inhibition, membrane permeability, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, lipopolysaccharide, OmpA, antimicrobial activity, bacterial clearance, C-terminal domain
- MeSH terms
- Animals, Bacterial Outer Membrane Proteins, Bronchoalveolar Lavage Fluid, Cell Division, Cell Membrane Permeability, Dactinomycin, Escherichia coli, Escherichia coli Infections, Fluorescent Dyes, Gram-Negative Bacteria, Humans, Mice, Inbred C3H, Microbial Sensitivity Tests, Respiratory Tract Infections, Rats, Sprague-Dawley, Mice, Knockout, Genetic Predisposition to Disease, Collectins, Pulmonary Surfactant-Associated Protein A, Pulmonary Surfactant-Associated Protein D, Mice, Rats
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