The obtained 3-amidoquinuclidine QACs showed a broad range of antibacterial activities related to the hydrophobic-hydrophilic balance of the QAC structures. Here, we report the synthesis and structure-function study of three structurally distinct series of naturally derived soft QACs. Recent studies of the structure–activity relationship suggest that the introduction of the amide functional group into QAC structures results in soft variants that retain their antimicrobial properties while opening the possibility of fine-tuned activity regulation. However, due to the growing trend of bacterial resistance and high toxicity of QACs, research in this field remains a pressing matter. Quaternary ammonium compounds (QACs) are among the most effective antimicrobial agents that have been used for more than a century. Although CCCP is an experimental agent with no therapeutic value clinically, further studies are necessary to decipher the mechanisms underlying the CST-CCCP synergy to inform the development of adjuvants that could be therapeutically effective in CST-resistant infections. We concluded that CCCP reverse CST resistance in CST-resistant Enterobacteriaceae. Eight isolates tested positive for the MEM-CCCP disc synergy test. Addition of CCCP reversed resistance to CST, TGC, IMP, and MEM in 44, three, zero, and zero isolates respectively CST had the highest mean minimum inhibitory concentration (MIC) fold change (193.12 p-value<0.0001) post CCCP compared to that of MEM (1.70), IMP (1.49) and TGC (1.16). Results and conclusions: Susceptibility to MEM, imipenem (IMP), CST, and TGC was found in only two, zero, 17 and nine isolates respectively. oxytoca/michiganensis (n=2) with known carbapenem resistance mechanisms and undescribed CST and TGC resistance mechanisms were subjected to broth microdilution and meropenem (MEM) disc synergy test in the presence and absence of carbonyl cyanide m-chlorophenylhydrazine (CCCP), a H+ conductor (protonophore). (n=15), Serratia marcescens (n=12), Citrobacter freundii (n=8), Escherichia coli (n=2), and K. Methods: Sixty-three clinical Enterobacteriaceae isolates comprising of Klebsiella pneumoniae (n=24), Enterobacter spp. Hence, the quest to find other agents that will synergistically restore the efficacy of these antibiotics have increased. However, resistance to these reserve antibiotics are increasingly being reported worldwide. Background: Carbapenems (CAR), colistin (CST), and tigecycline (TGC) alone or in combination therapy has become the last-resort antibiotics for treating infections caused by multidrug resistant (MDR) bacteria.
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