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

Abstract

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.

Rapid Quantitative Analysis of Metabolites in Kimchi Using LC-Q-Orbitrap MS

“… 28 2-Hydroxyisocaproic acid is produced through the leucine degradation pathway, and it was effective in inhibiting the growth of tested Gram-positive and Gram-negative bacteria. 29 HICA was not detected in the initial stage of kimchi fermentation. However, it was detected at a level of 0.241 mMol in the 1st week and detected approximately twice as much in the 2nd week at 0.486 mMol.…”

“…2-Hydroxyisocaproic acid and 3-phenyl lactic acid are known to be functional substances produced via the LAB metabolism of kimchi . 2-Hydroxyisocaproic acid is produced through the leucine degradation pathway, and it was effective in inhibiting the growth of tested Gram-positive and Gram-negative bacteria . HICA was not detected in the initial stage of kimchi fermentation.…”

Commensal Lactobacilli Metabolically Contribute to Cervical Epithelial Homeostasis in a Species-Specific Manner

“…Clinical studies have found that high concentrations of valine, leucine, and isoleucine are correlated with a high prevalence of lactobacilli in healthy pregnant women ( 101 , 102 ). Interestingly, our study indicated that, relative to mock-inoculated controls, all lactobacilli produced levated levels of branched-chain amino acids or related metabolites, such as 2-hydroxy-3-methylvalerate and alpha-hydroxyisocaproate, which are putative antimicrobial properties ( 103 ). Others have observed metabolites such as glycerophospholipids being positively correlated with Lactobacillus abundance ( 104 ).…”

Valorization of Spent Sugarcane Fermentation Broth as a Source of Phenolic Compounds

“…All compounds are listed in decreasing order of signal intensity. The highest compounds identified in negative ionization mode were the quinoxalines xanthurenic acid and kynurenic acid, along with the phenyllactic and leucinic acids (Table 6), two important antimicrobial compounds [36,37]. The highest compounds identified in positive ionization mode were tricin 7-rhamnosyl-(1->2)-galacturonide, a tricin derivative, two isomers of 6-hydroxyluteolin 6,4 -dimethyl ether 7-rutinoside, and the vitamin riboflavin (Table 7).…”

“…Besides the high antioxidant activity of the final extract, antimicrobial activity could have also possibly been attained by the presence of specific organic acids such as phenyllactic and leucinic acids [36,37]. In the same way, the amino acids and peptides present play important roles in action as antimicrobial, antithrombotic, antihypertensive, opioid, immunomodulatory, antioxidant, and mineral binding agents [39].…”