Inhibition of multi-drug resistant Staphylococci by sodium chlorate and select nitro- and medium chain fatty acid compounds

Authors: BOŽIC, ALEKSANDAR - University Of Novi Sad; Anderson, Robin; ARZOLA-ALVAREZ, CLAUDIO - Universidad Autonoma De Chihuahua; RUIZ-BARRERA, OSCAR - Universidad Autonoma De Chihuahua; CORRAL-LUNA, AGUSTIN - Universidad Autonoma De Chihuahua; CASTILLO-CASTILLO, YAMICELA - Universidad Autonoma De Chihuahua; ARZOLA-RUBIO, ALEJANDRO - Universidad Autonoma De Chihuahua; Poole, Toni; Harvey, Roger; Hume, Michael; Beier, Ross; Nisbet, David

Submitted to: Journal of Applied Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/20/2019
Publication Date: 2/25/2019
Citation: Božic, A., Anderson, R.C., Arzola-Alvarez, C., Ruiz-Barrera, O., Corral-Luna, A., Castillo-Castillo, Y., Arzola-Rubio, A., Poole, T.L., Harvey, R.B., Hume, M.E., Beier, R.C., Nisbet, D.J. 2019. Inhibition of multi-drug resistant Staphylococci by sodium chlorate and select nitro- and medium chain fatty acid compounds. Journal of Applied Microbiology. 126(5):1508-1518. https://doi.org/10.1111/jam.14232.
DOI: https://doi.org/10.1111/jam.14232

Interpretive Summary: Staphylococcus aureus are recognized as important pathogens of humans, livestock, and other animals, and the recent emergence of staphylococcal strains expressing antibiotic resistance in food-producing livestock has raised concerns of greater health risks to livestock workers and consumers of potentially contaminated foods. The aim of this study was to determine and compare the antimicrobial effects of six different potential antimicrobial compounds against representative antibiotic-resistant staphylococci. Three antibiotic-resistant Staphylococcus aureus and two other species of staphylococci were grown in a rich growth-supporting broth that had either been untreated (control) or treated with the potential inhibitors. Results revealed that a compound called 2-nitropropanol was the most potent and persistent of all the compounds tested, achieving 58 to 99% decreases in growth rate and total amount of growth when compared to untreated controls. Growth inhibition by cultures treated solely with two other compounds, nitroethane or chlorate, did not persist, with adaption occurring by different mechanisms after 7 to 8 h incubation. Adaption did not occur in cultures co-treated with nitroethane and chlorate. Three medium chain fatty acid compounds that were tested had only modest effects on all but one of the staphylococci tested. Results from this study suggest that the differential antimicrobial activities exhibited by the mechanistically dissimilar inhibitors against methicillin-resistant staphylococci may yield opportunities to combine the different treatments to overcome their individual limitations and broaden their activity against other mastic and dermal pathogens. Ultimately, this research may lead to the development of new antimicrobial strategies to help livestock producers control important staphylococcal pathogens in their animals, thereby helping them to produce wholesome meat and milk at less cost for the American consumer.

Technical Abstract: The aims of this study were to determine the antimicrobial effects of 5 mM sodium chlorate, 9 mM nitroethane or 2-nitropropanol, as well as lauric acid, myristic acid, and the glycerol ester of lauric acid Lauricidin®, each at 5 mg/mL, against representative methicillin-resistant staphylococci, which are important mastitic- and opportunistic dermal-pathogens of humans and livestock. Three methicillin-resistant Staphylococcus aureus (MRSA) and two methicillin-resistant coagulase-negative staphylococci were cultured at 39 deg C in 5 mM nitrate-supplemented half-strength Brain Heart Infusion (BHI) broth treated without or with the potential inhibitors. Results revealed that 2-nitropropanol was the most potent and persistent of all the compounds tested, achieving 58 to 99% decreases in mean bacterial specific growth rates and maximum optical densities when compared to untreated controls, with S. aureus strain CP being the most insensitive. Growth inhibition by cultures treated solely with nitroethane and chlorate did not persist, with adaption occurring by different mechanisms after 7 to 8 h incubation. Adaption did not occur in cultures co-treated with nitroethane and chlorate. The medium chain fatty acid compounds had only modest effects on all but one of the staphylococci tested, the exception being the coagulase-negative Staphylococcus epidermidis strain NKR1. Results from this study suggest that the differential antimicrobial activities exhibited by the mechanistically dissimilar inhibitors against methicillin-resistant staphylococci revealed potential opportunities to combine the different treatments to overcome their individual limitations and broaden their activity against other mastitic and dermal pathogens.