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

Huixing Wu, Alexander Kuzmenko, Sijue Wan, Lyndsay Schaffer, Alison Weiss, James H. Fisher, Kwang Sik Kim, Francis X. McCormack

Research output: Contribution to journalArticle

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, Klebsiellapneumoniae, and Enterobacteraerogenes. 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.

Original languageEnglish (US)
Pages (from-to)1589-1602
Number of pages14
JournalJournal of Clinical Investigation
Volume111
Issue number10
DOIs
StatePublished - May 2003

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Pulmonary Surfactant-Associated Protein D
Pulmonary Surfactant-Associated Protein A
Gram-Negative Bacteria
Permeability
Membranes
Growth
Collectins
Escherichia coli K12
Escherichia coli
Lipopolysaccharides
Pulmonary Surfactant-Associated Proteins
Cell Membrane Permeability
Lung
Recombinant Proteins
Macrophages
Calcium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wu, H., Kuzmenko, A., Wan, S., Schaffer, L., Weiss, A., Fisher, J. H., ... McCormack, F. X. (2003). Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. Journal of Clinical Investigation, 111(10), 1589-1602. https://doi.org/10.1172/JCI200316889

Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. / Wu, Huixing; Kuzmenko, Alexander; Wan, Sijue; Schaffer, Lyndsay; Weiss, Alison; Fisher, James H.; Kim, Kwang Sik; McCormack, Francis X.

In: Journal of Clinical Investigation, Vol. 111, No. 10, 05.2003, p. 1589-1602.

Research output: Contribution to journalArticle

Wu, Huixing ; Kuzmenko, Alexander ; Wan, Sijue ; Schaffer, Lyndsay ; Weiss, Alison ; Fisher, James H. ; Kim, Kwang Sik ; McCormack, Francis X. / Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 10. pp. 1589-1602.
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