Propionic acid and its esterified derivative suppress the growth of methicillin-resistant Staphylococcus aureus USA300

Abstract

Previously, we demonstrated that Propionibacterium acnes, a human skin commensal bacterium, ferments glycerol into short-chain fatty acids, including propionic acid. Propionic acid suppressed the growth of Staphylococcus aureus USA300, a community-acquired methicillin-resistant bacterium, in vitro and in vivo. In this study, it is demonstrated that the anti-USA300 activity of propionic acid persisted after buffering the acid with 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid. This suggests that the growth suppression of USA300 mainly resulted from the antimicrobial activity of propionic acid per se and not from the acidity of the medium. In addition, proprionic acid significantly reduced the intracellular pH of USA300 and exhibited broad-spectrum antimicrobial activity against Escherichia coli and Candida albicans. P. acnes showed a higher tolerance to propionic acid. Next, an esterified derivative of propionic acid was synthesised. Propionic acid and the esterified derivative were equivalent in their efficacy to suppress the growth of USA300 in vitro. The esterified derivative thus provides an alternative to propionic acid as an antimicrobial agent against S. aureus.

A Precision Microbiome Approach Using Sucrose for Selective Augmentation of Staphylococcus epidermidis Fermentation against Propionibacterium acnes

“…As shown in Figure 3, four SCFAs were produced in the fermented media of S. epidermidis . Results in our previous papers demonstrated that pH buffering does not influence the antimicrobial activities of SCFAs [15]. Furthermore, SCFAs can passively diffuse through the cell wall of bacteria and kill bacteria by lowering the intracellular pH [8].…”

“…Our previous studies have demonstrated that a co-drug—butyric acid 2-(2-butyryloxyethoxy) ethyl ester—can release two active butyric acids in mice (data not shown). A co-drug—propionic acid 2-(2-propionyloxy-ethoxy)-ethyl ester—exerts antimicrobial activity [15]. Application of these co-drugs onto acne lesions may conquer the drawbacks of SCFAs with short half-lives for acne treatments.…”

The skin microbiome is different in pediatric versus adult atopic dermatitis

“…7 Additionally, metabolites of adult-associated skin commensals can decrease skin pH and enhance antimicrobial activities, thus suppressing adherence and growth of S. aureus in human keratinocytes. 4, 8, 9 …”

Studies on the role of the skin microbiome in healthy skin and under pathogenic conditions

“…However, measurements in other, more easily accessible organs (e.g., the colon), where fermenting bacterial species are present suggests that PA levels can be as high as 20-140 mM (Garland SH 2001). These concentrations are sufficient to control pathogenic microbes: minimal bactericidal or fungicidal PA concentrations for different species were found to be 10-25 mM (Wang Y 2014). Based on these data, we chose PA concentrations of 1-10mM for our in vitro experiments that was in a range often used by other investigators (Allaker RP 1985).…”

“…In addition, PA exhibits antimicrobial properties that may be independent of its acidic nature (Wang Y 2014). High PA concentrations, however, may also have deleterious effects, leading to cellular damage and, thus, compromising the integrity of the epidermal barrier.…”