Chamomile oil and apigenin as novel modulators of mexA, mexB, mexR, and oprM efflux pump genes in multidrug-resistant Pseudomonas aeruginosa

Recent studies have shown that antimicrobial resistance has become a great threat. This study focuses on and investigates the effect of some natural compounds on the expression of efflux pump genes that play an important role in antimicrobial resistance in Pseudomonas aeruginosa. Among the 93 Pseudomonas aeruginosa that were isolated from different clinical samples, 20% were multidrug-resistant, 32% were extensively drug-resistant, and 2% were pandrug-resistant. Identification of the isolates was done using 16S rRNA gene amplification and sequencing. GC-MS analysis of chamomile oil revealed (is-.beta.-Farnesene) as the major component. Minimum inhibitory concentration values of each of apigenin, chamomile oil, and ceftazidime were evaluated for five of the isolates. Bacterial growth curve analysis revealed a decline in bacterial growth after treatment with sub-MIC levels of chamomile oil and apigenin. The gene expression of each mexA, mexB, mexR, and oprM efflux pump gene in the bacterial isolates using quantitative PCR was evaluated in untreated and treated isolates with a sub-MIC value of apigenin and chamomile oil. Chamomile oil significantly reduced the expression of all four genes. On the other hand, apigenin downregulated most genes but upregulated mexA in two isolates and mexB in one isolate. Meanwhile, Chamomile oil exhibited stronger downregulation of efflux pump genes compared to apigenin, with fold changes ranging from 2.28 to 14.3. Accordingly, these novel findings suggest that chamomile oil and apigenin can have a significant effect on inhibiting efflux pump gene expression, thus combating multidrug-resistant P. aeruginosa, and offering new avenues for developing effective natural therapeutic adjuvants to overcome antibiotic resistance. This is preliminary evidence for the gene regulatory potential of chamomile oil and apigenin.