Luteolin 4`-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo

The multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for developing new potential antimicrobials. This research was inspected if luteolin 4’-neohesperidoside (L4N) has antibacterial and synergistic activity against four antibiotic-resistant pathogens; Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, fosA positive shiga toxin producing Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus. In vitro antimicrobial susceptibility testing revealed a highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), K. pneumoniae (MIC of 53.33 ± 8.47 µg/mL) and STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activity. Prodigious synergistic combination was clearly noted with gentamycin (GEN) against Gram-negative bacteria. In case of B. cereus, combination of vancomycin (VAN) with L4N could inhibit efficiently bacterial growth despite being VAN resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding, and colonization. Treatment could significantly diminish the levels of pro-inflammatory marker, tumor necrosis factor-alpha (TNF-α), and immunoglobulin (IgM). Additionally, renal, and pulmonary lesions were remarkably enhanced with a significant lowering of bacterial loads inside the tissues. Finally, this study strongly presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti-K. pneumoniae potential, which is reported for the first time.