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Abstract

Galangin and quercetin can be used as a promise route against infections of Gram negative bacteria (GNB) which recorded high incidence in patients with acute myeloid leukemia (AML) due to their immunocompromised state. This study assessed the antibacterial activity of galangin and quercetin against four species of GNB collected from AML patients by determining of sub-minimum inhibitory concentrations (sub-MICs) of these flavonoids. Then, the sub-MICs of both flavonoid agents were applied to evaluate their antibacterial effect on gene expression levels targeting four of porin encoding genes included ompK36 for Klebsiella pneumoniae, ompA for Escherichia coli, oprD2 for Pseudomonas aeruginosa, and oprD for Acinetobacter baumannii. The microbiological tests for 132 urine samples yielded 27 (20.45%) isolates of GNB grouped as 10 (37.03%) K. pneumoniae, 8 (29.62%) E. coli, 5 (18.51%) P. aeruginosa, and 4 (14.81%) A. baumannii. The antimicrobial susceptibility for eight antibiotics from different classes showed these GNB isolates exhibited high resistance rates (80-90%) for the most of these agents. Meropenem and cefoxitin were the most effective agents against all GNB. The multidrug resistance (MDR) pattern was demonstrated among 23 (85.18%) of GNB. Galangin and quercetin exhibited bacteriostatic effect against species of MDR GNB at MICs of 7.8-125 μg/mL for galangin and 7.8-500 μg/mL for quercetin in which galangin statistically demonstrated higher antibacterial efficacy against MDR GNB than quercetin. Besides, sub-MICs of both flavonoids reduced the gene expression levels of the targeted porin encoding genes except ompA from E. coli isolates. The downregulation of these genes was mainly implicated in exhibiting MDR patterns among GNB by limiting the entry of antimicrobials across the membrane. Galangin and quercetin can potentially target risk infections caused by MDR GNB which are resistant for most commonly utilized antibiotics; therefore, these flavonoids can be employed as a suitable alternative choice over common ineffective antibiotics.

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