2‐hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species

Abstract

The amino acid derivative 2-hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml(-1) . Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml(-1) was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad-spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections.

A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

“…HICA was most active against C. albicans biofilms at acidic pH, in line with previous studies where planktonic cultures were used [43], [44]. The main focus of the present study was to investigate the anti-biofilm efficacy of HICA against various comparators whereby it was critical to grow the biofilms under standardised conditions before treatment at acidic and neutral conditions.…”

“…Recent studies from our group show promising efficacy of D,L-2-hydroxyisocaproic acid (HICA) against the growth of a spectrum of planktonically grown pathogenic bacteria and fungi including C. albicans , C. glabrata and C. tropicalis [43], [44]. HICA is a α-hydroxy-aminoacid and a leucine metabolite, which is produced by Lactobacillus species and also found in human muscle and connective tissues [45]–[47].…”

2‐Hydroxyisocaproic acid is bactericidal in human dental root canals ex vivo

“…) and several Candida species (Sakko et al . ), the present findings confirm the potential use of HICA paste as an interappointment medication in root canal treatment.…”

“…2-hydroxyisocaproic acid (HICA) is a protein fermentation product, which has broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria (Hietala et al 1979, Sakko et al 2012, and against fungal species (Sakko et al 2014) and Candida albicans biofilms (Nieminen et al 2014a). It also has anti-inflammatory activity (Nieminen et al 2014b).…”

dl-2-Hydroxyisocaproic Acid Attenuates Inflammatory Responses in a Murine Candida albicans Biofilm Model

“…The efficacy of HICA against a spectrum of planktonically grown bacteria and fungi has been reported (18,19). HICA is an ␣-hydroxy amino acid produced during Lactobacillus fermentation and is also found in human tissues (20,21).…”