Pulmonary Surfactant Promotes Virulence Gene Expression and Biofilm Formation in Klebsiella pneumoniae

The interactions between and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this...

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Bibliographic Details
Published in:Infection and immunity 2018-07, Vol.86 (7)
Main Authors: Willsey, Graham G, Ventrone, Sebastian, Schutz, Kristin C, Wallace, Aaron M, Ribis, John W, Suratt, Benjamin T, Wargo, Matthew J
Format: Article
Language:English
Subjects:
Amino Acids, Branched-Chain - biosynthesis
Animals
Biofilms - drug effects
Biogenic Polyamines - physiology
Fimbriae, Bacterial - physiology
Gene Expression Regulation, Bacterial - drug effects
Host-Pathogen Interactions
Klebsiella pneumoniae - drug effects
Klebsiella pneumoniae - pathogenicity
Klebsiella pneumoniae - physiology
Male
Mice
Mice, Inbred C57BL
Molecular Pathogenesis
Pulmonary Surfactants - pharmacology
Virulence - genetics
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Summary:The interactions between and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional response of MGH 78578 to purified pulmonary surfactant. This work revealed changes within the transcriptome that likely contribute to host colonization, adaptation, and virulence Notable transcripts expressed under these conditions include genes involved in capsule synthesis, lipopolysaccharide modification, antibiotic resistance, biofilm formation, and metabolism. In addition, we tested the contributions of other surfactant-induced transcripts to survival using engineered isogenic KPPR1 deletion strains in a murine model of acute pneumonia. In these infection studies, we identified the MdtJI polyamine efflux pump and the ProU glycine betaine ABC transporter to be significant mediators of survival within the lung and confirmed previous evidence for the importance of leucine synthesis to bacterial survival during infection. Finally, we determined that pulmonary surfactant promoted type 3 fimbria-mediated biofilm formation in and identified two surfactant constituents, phosphatidylcholine and cholesterol, that drive this response. This study provides novel insight into the interactions occurring between and the host at an important infection site and demonstrates the utility of purified lung surfactant preparations for dissecting host-lung pathogen interactions .
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00135-18