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Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae.


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Title: Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae.
Authors: Nakamura, Shigeki / Shchepetov, Mikhail / Dalia, Ankur B / Clark, Sarah E / Murphy, Timothy F / Sethi, Sanjay / Gilsdorf, Janet R / Smith, Arnold L / Weiser, Jeffery N
Issue Date: 6-Jan-2011
Publisher: Public Library of Science
Citation: PLoS Pathogens, 7(1), e1001247; 2011
Abstract: Non-typeable Haemophilus influenzae (NTHi), a common commensal of the human pharynx, is also an opportunistic pathogen if it becomes established in the lower respiratory tract (LRT). In comparison to colonizing isolates from the upper airway, LRT isolates, especially those associated with exacerbations of chronic obstructive pulmonary disease, have increased resistance to the complement- and antibody-dependent, bactericidal effect of serum. To define the molecular basis of this resistance, mutants constructed in a serum resistant strain using the mariner transposon were screened for loss of survival in normal human serum. The loci required for serum resistance contribute to the structure of the exposed surface of the bacterial outer membrane. These included loci involved in biosynthesis of the oligosaccharide component of lipooligosaccharide (LOS), and vacJ, which functions with an ABC transporter encoded by yrb genes in retrograde trafficking of phospholipids from the outer to inner leaflet of the cell envelope. Mutations in vacJ and yrb genes reduced the stability of the outer membrane and were associated with increased cell surface hyrophobicity and phospholipid content. Loss of serum resistance in vacJ and yrb mutants correlated with increased binding of natural immunoglobulin M in serum as well as anti-oligosaccharide mAbs. Expression of vacJ and the yrb genes was positively correlated with serum resistance among clinical isolates. Our findings suggest that NTHi adapts to inflammation encountered during infection of the LRT by modulation of its outer leaflet through increased expression of vacJ and yrb genes to minimize recognition by bactericidal anti-oligosaccharide antibodies.
URI: http://hdl.handle.net/10069/24983
ISSN: 15537366
DOI: 10.1371/journal.ppat.1001247
PubMed ID: 21253576
Rights: © 2011 Nakamura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/24983

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