Chemokine CCL28 is a potent therapeutic agent for oropharyngeal candidiasis.

In this study, we examine the in vivo Candida killing capacity of CCL28 in oropharyngeal candidiasis (OPC), as well as the spectrum and mechanism of anti-Candida activity. In the mouse model of OPC, application of wild type CCL28 reduces oral fungal burden in severely immunodeficient mice without causing excessive inflammation or altering tissue neutrophil recruitment. CCL28 is effective against multiple clinical strains of C. albicans. Polyamine protein transporters are not required for CCL28 anti-Candida activity. Both structured and unstructured CCL28 proteins show rapid and sustained fungicidal activity that is superior to clinical anti-fungal agents. Application of wild type CCL28 to C. albicans results in membrane disruption as measured by solute movement, enzyme leakage and induction of negative Gaussian curvature on model membranes. Membrane disruption is reduced in CCL28 lacking the functional C-terminal tail. Our results strongly suggest that CCL28 can exert antifungal activity in part via membrane permeation and has potential for development as an anti-Candida therapeutic agent without inflammatory side effects. PMID: 32423961 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research