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Na+/H+ antiport is essential for Yersinia pestis virulence

Yusuke Minato1, Amit Ghosh, Wyatt J Faulkner

  • 1Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.

Infection and Immunity
|June 19, 2013
PubMed

Insights

Na(+)/H(+) antiporters are crucial for Yersinia pestis survival in blood. Disrupting these transporters, NhaA and NhaB, attenuates Y. pestis virulence, suggesting they are potential drug targets.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogen Physiology

Background:

  • Na(+)/H(+) antiporters are essential membrane proteins regulating cellular ion balance.
  • Yersinia pestis is a dangerous bacterial pathogen causing plague.
  • Understanding Y. pestis survival mechanisms is critical for developing new treatments.

Purpose of the Study:

  • To investigate the role of Na(+)/H(+) antiport in Yersinia pestis virulence.
  • To determine if Na(+)/H(+) antiporter genes (nhaA and nhaB) are essential for Y. pestis survival in host environments.

Main Methods:

  • Generating Y. pestis double deletion mutants lacking nhaA and nhaB genes.
  • Assessing mutant survival in vivo (plague model) and ex vivo (blood, serum).
  • Evaluating growth in artificial serum (Opti-MEM) and rich media under specific ionic and pH conditions.

Main Results:

  • Y. pestis strains lacking nhaA and nhaB were completely attenuated in a plague model.
  • The double deletion mutant exhibited significantly reduced survival in blood and serum.
  • Complementation with nhaA or nhaB restored blood survival, and growth inhibition was observed in serum-like media.

Conclusions:

  • Intact Na(+)/H(+) antiport (NhaA and NhaB) is indispensable for Y. pestis survival in the bloodstream.
  • These antiporters represent promising noncanonical drug targets for Y. pestis infections.
  • The findings may extend to other blood-borne bacterial pathogens.

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