Macroenvironmental interactions as driving indicators for detecting tetracycline resistance spread among A. hydrophila exposure to environmentally relevant oxytetracycline levels

There have been efforts dedicating to investigating the effect of high levels of oxytetracycline (OTC) on tetracycline (TC) resistance among zoonotic pathogen Aeromonas hydrophila (AH), an antibiotic-resistant bacterial indicator. However, the dynamic behavior of TC-resistant AH in response to environmentally relevant OTC concentrations at a population-level has not been fully understood. Here we developed a bacterial population dynamic model to quantify TC-resistant AH posed by OTC-dependent resistance selection pressure. The key environmental factors known as water temperature, water activity, and pH were incorporated into model to produce pattern-oriented simulation outcomes. We estimated resistance acquisition number (R-0) and showed that R-0 was >1 at water temperature <26 degrees C, indicating coexistence of resistant- and susceptible-AH. Sensitivity tests revealed that cell density-dependent conjugation rate indicated crucial for influencing R-0 estimation. Our results also indicated that maximum fraction of TC-resistant AH was mostly affected by temperature/activity in water and increased with increasing of OTC concentrations. We estimated OTC concentrations causing 50 % maximum fold-change of TC-resistant AH fraction ranging from 7 to 19 mu g/L. Our findings suggest that control of TC resistance in AH requires particularly attention to water with temperature 26 degrees C lower, water activity 0.95 higher with pH similar to 5-8. Our mechanistic framework provides a useful tool-kit to improve our understanding of the critical role of OTC stress-induced macroenvironmental interactions in a TC resistance AH system and highlights the potential for antimicrobial management to promote resilience in aquatic ecosystems.