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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
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Contribution of Hfq to gene regulation and virulence in Histophilus somni

Dianjun Cao1, Bindu Subhadra1, Yue-Jia Lee1

  • 1Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, Long Island University, Brookville, New York, USA.

Infection and Immunity
|February 23, 2024
PubMed

Insights

The bacterial regulatory protein Hfq is crucial for Histophilus somni virulence. Deleting Hfq in H. somni significantly altered its lipooligosaccharide structure and reduced its ability to cause disease in cattle and mice.

Area of Science:

  • Bacteriology
  • Molecular Biology
  • Veterinary Microbiology

Background:

  • Histophilus somni is a major bacterial pathogen causing respiratory and systemic diseases in cattle.
  • Virulence factors of H. somni are known, but their regulatory mechanisms remain largely uncharacterized.
  • The post-transcriptional regulatory protein Hfq is a potential key regulator of bacterial virulence.

Purpose of the Study:

  • To investigate the role of Hfq in H. somni phenotype and virulence.
  • To characterize an Hfq deletion mutant (H. somni 2336Δhfq) and compare it to the wild-type strain.

Main Methods:

  • Construction and phenotypic analysis of an H. somni hfq deletion mutant.
  • Comparative analysis of protein and carbohydrate profiles, serum susceptibility, and intracellular survival in bovine monocytes.
  • Transcriptomic analysis (RNA sequencing) of the mutant and wild-type strains.
  • Virulence studies in mouse septicemia and calf respiratory challenge models.

Main Results:

  • The H. somni 2336Δhfq mutant exhibited a truncated, non-sialylated lipooligosaccharide (LOS) structure.
  • The mutant showed increased susceptibility to serum-mediated and intracellular killing.
  • Transcriptomic analysis revealed significant differential expression of genes involved in polysaccharide synthesis and virulence.
  • The H. somni 2336Δhfq mutant was attenuated in mouse and calf models, with reduced bacterial recovery and lung pathology in calves.

Conclusions:

  • Hfq plays a significant role in regulating H. somni virulence factors.
  • Hfq influences lipooligosaccharide biosynthesis and sialylation, impacting bacterial survival and pathogenicity.
  • Targeting Hfq could be a potential strategy for controlling H. somni infections in cattle.
Keywords:
HfqHistophilus somnibiofilmgene regulationlipooligosaccharidevirulence

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