The Postbiotic Activity of Lactobacillus paracasei 28.4 Against Candida auris

Abstract

<i>Candida auris</i> has emerged as a medically important pathogen with considerable resistance to antifungal agents. The ability to produce biofilms is an important pathogenicity feature of this species that aids escape of host immune responses and antimicrobial agents. The objective of this study was to verify antifungal action using <i>in vitro</i> and <i>in vivo</i> models of the <i>Lactobacillus paracasei</i> 28.4 probiotic cells and postbiotic activity of crude extract (LPCE) and fraction 1 (LPF1), derived from <i>L. paracasei</i> 28.4 supernatant. Both live cells and cells free supernatant of <i>L. paracasei</i> 28.4 inhibited <i>C. auris</i> suggesting probiotic and postbiotic effects. The minimum inhibitory concentration (MIC) for LPCE was 15 mg/mL and ranges from 3.75 to 7.5 mg/mL for LPF1. Killing kinetics determined that after 24 h treatment with LPCE or LPF1 there was a complete reduction of viable <i>C. auris</i> cells compared to fluconazole, which decreased the initial inoculum by 1-logCFU during the same time period. LPCE and LPF1 significantly reduced the biomass (<i>p</i> = 0.0001) and the metabolic activity (<i>p</i> = 0.0001) of <i>C. auris</i> biofilm. There was also a total reduction (~10⁸ CFU/mL) in viability of persister <i>C. auris</i> cells after treatment with postbiotic elements (<i>p</i> < 0.0001). In an <i>in vivo</i> study, injection of LPCE and LPF1 into <i>G. mellonella</i> larvae infected with <i>C. auris</i> prolonged survival of these insects compared to a control group (<i>p</i> < 0.05) and elicited immune responses by increasing the number of circulating hemocytes and gene expression of antimicrobial peptide galiomicin. We concluded that the <i>L. paracasei</i> 28.4 cells and postbiotic elements (LPCE and LPF1) have antifungal activity against planktonic cells, biofilms, and persister cells of <i>C. auris</i>. Postbiotic supplementation derived from <i>L. paracasei</i> 28.4 protected <i>G. mellonella</i> infected with <i>C. auris</i> and enhanced its immune status indicating a dual function in modulating a host immune response.