Abstract
The aim of this study is to investigate the antimicrobial synergistic effect against Campylobacter jejuni, a leading foodborne pathogen that causes human gastroenteritis, by cinnamon oil, encapsulated curcumin, and zinc oxide nanoparticles (ZnO NPs). We compared three approaches to study the antimicrobial interactions, including the time-killing method, the fractional inhibitory concentration index (FICI) method, and a mathematical concentration-effect model. Isobologram analysis was performed to evaluate the synergy in different combinations, and a median-effect equation was applied to identify the combinations of synergistic effects at median, bacteriostatic, and bactericidal reduction levels. The time-killing method overestimated the synergistic interaction between antimicrobials, while the FICI method failed to detect an existing synergistic phenomenon. This lack of accuracy and sensitivity was mainly due to combining antimicrobials without a deep understanding of their concentration-effect relationships. Our results showed that each antimicrobial had a unique concentration-effect curve. Specifically, encapsulated curcumin showed a sharp sigmoidal curve unlike cinnamon oil and ZnO NPs. A mathematical model was applied to study the interaction between antimicrobials with a different shape of concentration-effect curve. We observed an additive effect of cinnamon oil/ZnO NPs and synergistic interactions of other binary combinations (cinnamon oil/encapsulated curcumin and ZnO NPs/encapsulated curcumin). The tertiary combination of cinnamon oil/ZnO NPs/encapsulated curcumin at IC25 (additive line <1-log CFU/mL) presented the greatest synergistic effect by reducing the bacterial population over 8-log CFU/mL. This mathematical model provided an alternative strategy to develop a new antimicrobial strategy.
Highlights
Campylobacter is one of the leading bacterial causes of human infectious diseases worldwide
The maximum theoretical additive effect used in this study was 82% (
The 0.5 × minimum bactericidal concentrations (MBC) of all single antimicrobials had a mild effect with ≤1 log reduction and no significant effect compared to the control groups at all time points (P > 0.05) (Figure 1)
Summary
Campylobacter is one of the leading bacterial causes of human infectious diseases worldwide. Campylobacter jejuni is the most common species that accounts for ∼80% of campylobacteriosis with a relatively low infectious dose (∼500–800 cells) (Nachamkin et al, 2008). C. jejuni infections usually lead to non-fatal and self-limiting gastroenteritis, including watery diarrhea, nausea, and vomiting; severe autoimmune neurological disorders such as Guillain–Barré syndrome may occur in immunocompromised individuals (Kaakoush et al, 2015). Transmission of C. jejuni is commonly through the consumption of meat product (e.g., poultry and beef), raw milk, and/or contaminated drinking water. For all of these reasons, there is an urgent need to develop a new strategy of antimicrobial usage to reduce the prevalence of Campylobacter in the environment and agri-food products
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