**1. Introduction**

Microbial infections in critically ill patients are a global threat. With failing host defense, the use of antibiotics has taken the place for containment of those infections. Nevertheless, the microbes have also evolved with time to develop resistance against those drugs. This arm's race between antibiotic drugs and pathogens had led to the rise of multi-drug-resistant microbes, called "superbugs", which emphasizes the urgent need to develop new modes of treatment. Since antimicrobial peptides (AMPs) have evaded bacterial resistance for millions of years of evolution [1], AMPs could be a potential solution for antibiotic resistant "superbugs". Chromogranin A (CgA), the acidic and secretory proprotein [2,3], is proteolytically cleaved to generate several biologically important peptides, including Catestatin (CST: hCgA352–372) [4–12]. The 21 amino acid peptide CST (human: S352SMKLSFRARAYGFRGPGPQL372; bovine: R344SMRLSFRARGYGFRGPGLQL364) was identified in 1997 as a physiologic brake in catecholamine secretion, which acts by noncompetitive inhibition of nicotinic-cholinergic signaling [5,13–18]. CST is now established as a pleiotropic peptide [6,19,20]

**Citation:** Jati, S.; Mahata, S.; Das, S.; Chatterjee, S.; Mahata, S.K. Catestatin: Antimicrobial Functions and Potential Therapeutics. *Pharmaceutics* **2023**, *15*, 1550. https://doi.org/10.3390/ pharmaceutics15051550

Academic Editors: Scavello Francesco, Jean-Eric Ghia and Amiche Mohamed

Received: 1 April 2023 Revised: 9 May 2023 Accepted: 14 May 2023 Published: 20 May 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

The non-hemolytic antimicrobial (bacteria, fungus, and yeast) effects of CST (bCST1–15 aka cateslytin) were first reported in 2005, where CST was shown to act by penetrating fungal and yeast cell membranes [21]. The study showed that less than 10 μM peptide was required to kill the bacteria. Antibacterial activities were also reported for the two human variants of CST (G364S-CST and P370L-CST) [22] with minimal inhibitory concentration (MIC) of 1–20 μM [21]. Later, D-bCST1–15 (where L-amino acids were changed to D-amino acids: r344smrlsfrargygfr358) was shown to exert more potent antibacterial (both Grampositive and Gram-negative bacteria) effects than natural CST [23]. The present review will focus on the antimicrobial effects of CST, with special emphasis on the mechanisms underlying its antibacterial effects, therapeutic potential, and evolutionary conservation.
