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Hfe Permease and Haemophilus influenzae Manganese Homeostasis

Katherine Ganio1, Marufa Nasreen2,3, Zihao Yang2,3

  • 1Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.

ACS Infectious Diseases
|January 19, 2024
PubMed

Insights

Haemophilus influenzae uses the HfeA protein to acquire manganese, which is crucial for its survival against oxidative stress and virulence. This study reveals HfeA

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Haemophilus influenzae is a common bacterium in the human respiratory tract.
  • Oxidative stress is a major challenge for bacterial survival in host environments.
  • Iron and manganese are essential metals for bacterial growth and virulence.

Purpose of the Study:

  • To investigate the role of the hfeA gene in Haemophilus influenzae.
  • To elucidate the mechanism of manganese acquisition by H. influenzae.
  • To understand how manganese uptake contributes to H. influenzae virulence.

Main Methods:

  • Genetic disruption of the hfeA gene in H. influenzae.
  • Structural analysis of the HfeA protein and its metal-binding mechanism.
  • Assessing bacterial growth, enzyme activity, and survival under oxidative stress conditions.
  • Evaluating biofilm formation in the presence of superoxide.

Main Results:

  • The hfeA gene is essential for manganese recruitment via the HfeBCD transporter in H. influenzae.
  • Structural studies revealed a unique metal-binding mechanism in HfeA involving protein lobe rotation.
  • Disruption of hfeA led to reduced manganese acquisition, impaired growth, decreased manganese-superoxide dismutase activity, and altered survival in macrophages.
  • Changes in biofilm production were observed under superoxide stress.

Conclusions:

  • HfeA plays a critical role in H. influenzae manganese acquisition, impacting its virulence.
  • The HfeBCD permease system, particularly HfeA, is vital for combating oxidative stress.
  • Conserved hfeABCD genes in other Pasteurellaceae suggest similar functions in related pathogens.
Keywords:
ABC transporterHaemophilus influenzaeHi2019SBPhost–pathogenmetal homeostasissolute-binding proteinsuperoxide dismutase

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