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Assessing Respiratory Immune Responses to Haemophilus Influenzae
06:32

Assessing Respiratory Immune Responses to Haemophilus Influenzae

Published on: June 29, 2021

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

Shigeki Nakamura1, Mikhail Shchepetov, Ankur B Dalia

  • 1Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Plos Pathogens
|January 22, 2011
PubMed

Insights

Non-typeable Haemophilus influenzae (NTHi) develops serum resistance in the lower respiratory tract by altering its outer membrane. This adaptation helps NTHi evade immune responses during chronic obstructive pulmonary disease exacerbations.

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Non-typeable Haemophilus influenzae (NTHi) is a common bacterium that can cause lower respiratory tract (LRT) infections, particularly during chronic obstructive pulmonary disease (COPD) exacerbations.
  • Isolates from the LRT exhibit greater resistance to serum's bactericidal effects compared to upper airway colonizers.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying serum resistance in NTHi isolates from the LRT.
  • To identify bacterial genes and pathways involved in NTHi's survival against serum-mediated immune responses.

Main Methods:

  • Construction and screening of mariner transposon mutants in a serum-resistant NTHi strain for loss of serum survival.
  • Analysis of bacterial outer membrane composition, stability, hydrophobicity, and phospholipid content in wild-type and mutant strains.
  • Assessment of natural immunoglobulin M and monoclonal antibody binding to bacterial surface.

Main Results:

  • Mutations in loci involved in lipooligosaccharide (LOS) biosynthesis and the vacJ/yrb genes conferred serum sensitivity.
  • VacJ and yrb gene products are crucial for outer membrane stability and regulate phospholipid trafficking.
  • VacJ and yrb mutants showed increased cell surface hydrophobicity and phospholipid content, leading to reduced serum resistance.
  • Serum-resistant NTHi isolates demonstrated higher expression of vacJ and yrb genes.

Conclusions:

  • NTHi adapts to the inflammatory LRT environment by modulating its outer membrane composition, specifically through the vacJ and yrb genes.
  • Upregulation of vacJ and yrb enhances outer membrane stability and reduces recognition by bactericidal antibodies, contributing to NTHi's persistence in the LRT.
  • These findings provide insights into NTHi pathogenesis and potential therapeutic targets for LRT infections.

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