In Silico and In Vitro Investigations of Novel Strategies to Combat Drug‐Resistant <i>Comamonas aquatica</i>

Comamonas aquatica, an emerging nosocomial pathogen, poses significant clinical challenges through biofilm-mediated antimicrobial resistance. This study investigated the efficacy of cuminaldehyde combined with tetracycline against C. aquatica biofilms using an integrated approach. In silico predictions (PASS online, SwissADME, PROTOX 3.0, OSIRIS) indicated that cuminaldehyde exhibited favorable oral bioavailability with acceptable toxicity profiles, while tetracycline showed limited oral absorption due to molecular size and polarity constraints. Experimentally, individual minimum inhibitory concentrations (MICs) were determined as 300 μg/mL for cuminaldehyde and 0.2 μg/mL for tetracycline. The fractional inhibitory concentration index (FICI) of 0.66 demonstrated additive interactions between the compounds (cuminaldehyde and tetracycline). The result indicated that the combinatorial application of compounds exhibited enhanced antimicrobial potential against the test organism. Furthermore, co-application of cuminaldehyde and tetracycline was found to show increased antibiofilm potential against the same organism. The result showed that the biofilm inhibition under the influence of the combinatorial application could be attributed to the enhancement of bacterial cell membrane permeability and accumulation of intracellular reactive oxygen species. In a nutshell, the findings of this study highlight a promising strategy of using combinatorial therapy involving cuminaldehyde-tetracycline for dealing with biofilm-associated infections caused by C. aquatica.