Catestatin: Antimicrobial Functions and Potential Therapeutics

Author:

Jati Suborno1,Mahata Sumana2,Das Soumita3,Chatterjee Saurabh4ORCID,Mahata Sushil K.25

Affiliation:

1. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA

2. Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA

3. Department of Biomedical and Nutritional Science, University of Massachusetts Lowell, Lowell, MA 01854, USA

4. Department of Medicine, University of California Irvine, Irvine, CA 92697, USA

5. VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA

Abstract

The rapid increase in drug-resistant and multidrug-resistant infections poses a serious challenge to antimicrobial therapies, and has created a global health crisis. Since antimicrobial peptides (AMPs) have escaped bacterial resistance throughout evolution, AMPs are a category of potential alternatives for antibiotic-resistant “superbugs”. The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352–372; bCgA344–364) was initially identified in 1997 as an acute nicotinic-cholinergic antagonist. Subsequently, CST was established as a pleiotropic hormone. In 2005, it was reported that N-terminal 15 amino acids of bovine CST (bCST1–15 aka cateslytin) exert antibacterial, antifungal, and antiyeast effects without showing any hemolytic effects. In 2017, D-bCST1–15 (where L-amino acids were changed to D-amino acids) was shown to exert very effective antimicrobial effects against various bacterial strains. Beyond antimicrobial effects, D-bCST1–15 potentiated (additive/synergistic) antibacterial effects of cefotaxime, amoxicillin, and methicillin. Furthermore, D-bCST1–15 neither triggered bacterial resistance nor elicited cytokine release. The present review will highlight the antimicrobial effects of CST, bCST1–15 (aka cateslytin), D-bCST1–15, and human variants of CST (Gly364Ser-CST and Pro370Leu-CST); evolutionary conservation of CST in mammals; and their potential as a therapy for antibiotic-resistant “superbugs”.

Funder

National Institutes of Health

AFTD Holloway Postdoctoral Fellowship

Publisher

MDPI AG

Subject

Pharmaceutical Science

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