Selective combinatory effect of antibiotics with phytochemicals and synthetic analogues of plant-derived compounds against diarrhoea-causing and beneficial intestinal bacteria

Ing. B.Sc. Hayford Osei-Owusu

Disertační práce

Abstract:

Despite being treated and preventable, diarrhoea-associated morbidity and mortality remains an important public health concern among children and adults, especially in developing countries. In addition, antibiotic-associated gut dysbiosis is a significant health problem globally. The development of combinatory agents that increase the selective inhibitory effect (synergism) against diarrhoea-causing pathogens and, at the same time, have a lowered impact (antagonism) or no adverse action on the gut microbiota is therefore suggested as a new strategy effective for diarrhoea treatment and prevention. In this study, the in vitro selective combinatory effect of ciprofloxacin with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of alkaloid-related compounds) against selected standard diarrhoeagenic (Bacillus cereus, Enterococcus faecalis, Listeria monocytogenes, Shigella flexneri and Vibrio parahaemolyticus) and gut beneficial (Bifidobacterium adolescentis, Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, Lacticaseibacillus casei and Lacticaseibacillus rhamnosus) bacteria was assessed using broth microdilution assay. Also, the combined effect of tetracycline together with the above-mentioned alkaloid-related compounds was evaluated against strains of diarrhoea bacteria, including E. faecalis, Escherichia coli, L. monocytogenes, S. flexneri, V. parahaemolyticus, and Yersinia enterocolitica in vitro. The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). The preliminary screening results indicated that combinations of alkaloid-related compounds with ciprofloxacin produce strong synergistic interactions. Further experiments showed that the combinations of ciprofloxacin with nitroxoline, sanguinarine and zinc pyrithione exhibited synergistic effect against the diarrhoeic bacteria with FICI values ranging from 0.071 to 0.5 whereas antagonistic effect was achieved at FICI values ranging from 4.012 to 8.023 towards the Bifidobacterium strains. Furthermore, the aforementioned combinations exhibited no interaction on Lacticaseibacillus strains tested. Ciprofloxacin/zinc pyrithione produced the greatest synergistic action against S. flexneri, whereas strong antagonistic interaction was observed towards B. breve for ciprofloxacin-nitroxoline combinations. Among combinations of alkaloid-related compounds with other antibiotics, tetracycline, when combined with either nitroxoline, sanguinarine, or zinc pyrithione, demonstrated synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. These findings indicate that certain combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeal medications that may have lower or no effect on the gut microbiota. Nevertheless, studies focusing on their in vivo anti-diarrheal activity and safety are required before any consideration for utilization in human medicine.

Keywords

alkaloid-related compounds, antagonism, bacteria, diarrhoea, dysbiosis, gut microbiota, mortality, synergism

Jazyk práce: angličtina

Datum vytvoření / odevzdání či podání práce: 26. 9. 2024

Obhajoba závěrečné práce

• Vedoucí: prof. Ing. Ladislav Kokoška, Ph.D.
• Oponent: Karel Šmejkal, Bc., externi, Přemysl Landa, MUDr., externi, Jiří Killer, externi

Česká zemědělská univerzita v Praze

Fakulta tropického zemědělství

Doktorský studijní program / obor:
Zemědělská specializace / Tropical Agrobiology and Bioresource Management