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Targeting and inactivation of bacterial toxins by human defensins

  • Elena Kudryashova , Stephanie M. Seveau and Dmitri S. Kudryashov EMAIL logo
Published/Copyright: May 9, 2017

Abstract

Defensins, as a prominent family of antimicrobial peptides (AMP), are major effectors of the innate immunity with a broad range of immune modulatory and antimicrobial activities. In particular, defensins are the only recognized fast-response molecules that can neutralize a broad range of bacterial toxins, many of which are among the deadliest compounds on the planet. For a decade, the mystery of how a small and structurally conserved group of peptides can neutralize a heterogeneous group of toxins with little to no sequential and structural similarity remained unresolved. Recently, it was found that defensins recognize and target structural plasticity/thermodynamic instability, fundamental physicochemical properties that unite many bacterial toxins and distinguish them from the majority of host proteins. Binding of human defensins promotes local unfolding of the affected toxins, destabilizes their secondary and tertiary structures, increases susceptibility to proteolysis, and leads to their precipitation. While the details of toxin destabilization by defensins remain obscure, here we briefly review properties and activities of bacterial toxins known to be affected by or resilient to defensins, and discuss how recognized features of defensins correlate with the observed inactivation.

Acknowledgments

This work was supported by The OSU Public Health Preparedness for Infectious Diseases (PHPID) program (New Investigator Grant to D.S.K.), the National Institute of General Medical Sciences of the NIH under award number R01GM114666 (to D.S.K.), and the National Institute of Health under award R01AI107250 (to S.M.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Received: 2017-1-24
Accepted: 2017-4-18
Published Online: 2017-5-9
Published in Print: 2017-9-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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