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Antibacterial efficacy and possible mechanism of action of 2-hydroxyisocaproic acid (HICA)

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journal contribution
posted on 2023-05-03, 19:25 authored by Amila Pahalagedara, Steve Flint, Jon Palmer, Gale BrightwellGale Brightwell, Tanushree Gupta
The exploitation of natural antimicrobial compounds that can be used in food preservation has been fast tracked by the development of antimicrobial resistance to existing antimicrobials and the increasing consumer demand for natural food preservatives. 2-hydroxyisocaproic acid (HICA) is a natural compound produced through the leucine degradation pathway and is produced in humans and by certain microorganisms such as lactic acid bacteria and Clostridium species. The present study investigated the antibacterial efficacy of HICA against some important bacteria associated with food quality and safety and provided some insights into its possible antimicrobial mechanisms against bacteria. The results revealed that HICA was effective in inhibiting the growth of tested Gram-positive and Gram-negative bacteria including a multi-drug resistant P. aeruginosa strain in this study. The underlying mechanism was investigated by measuring the cell membrane integrity, membrane permeability, membrane depolarisation, and morphological and ultrastructural changes after HICA treatment in bacterial cells. The evidence supports that HICA exerts its activity via penetration of the bacterial cell membranes, thereby causing depolarisation, rupture of membranes, subsequent leakage of cellular contents and cell death. The current study suggests that HICA has potential to be used as an antibacterial agent against food spoilage and food-borne pathogenic bacteria, targeting the bacterial cell envelope.


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© 2022 Pahalagedara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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Journal title

PLoS One




Pahalagedara, A. S. N. W., Flint, S., Palmer, J., Brightwell, G., & Gupta, T. B. (2022). Antibacterial efficacy and possible mechanism of action of 2-hydroxyisocaproic acid (HICA). PLoS One, 17(4), e0266406.