Cholecalciferol, Ergosterol, and Cholesterol Enhance the Antibiotic Activity of Drugs

Abstract

Abstract. Background: This is the first report demonstrating the antibiotic-modifying activity of cholecalciferol. Aim: In this study, cholecalciferol was evaluated against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Methods: The antibacterial and modulatory effects of cholecalciferol, ergosterol, and cholesterol (8–512 μg/mL) were evaluated by microdilution assay against multiresistant bacterial strains. Results: Cholecalciferol, when combined with aminoglycosides, was more effective against P. aeruginosa, reducing the concentration of amikacin and gentamicin necessary to inhibit bacterial growth from 156.25 to 39.06 μg/mL and from 39.06 to 9.76 μg/mL, respectively. It is possible that cholecalciferol, due to its lipid-soluble nature, had a lipophilic interaction with the cell membrane, enhancing antibiotic uptake. Cholesterol and ergosterol were used to see if the mechanism of action of cholecalciferol was similar to that of these lipid compounds. Ergosterol and cholesterol increased aminoglycoside activity, where the effect was greater with higher subinhibitory concentration of sterol. Conclusions: There is no reported study on the use of cholesterol and ergosterol as modulators of antibiotics or any other drug, making this the first study in this area highlighting the interaction between cholesterol, ergosterol, and cholecalciferol with regard to modifying aminoglycoside activity.

Vitamin E as promising adjunct treatment option in the combat of infectious diseases caused by bacterial including multi-drug resistant pathogens – Results from a comprehensive literature survey

“…Vitamin D, for instance, displayed antibacterial effects against Porphyromonas gingivalis [36], Streptococcus mutans [37], and Helicobacter pylori [38]. In addition, synergistic antimicrobial effects of vitamin D in combination with distinct antibiotic compounds directed against MDR strains of P. aeruginosa and S. aureus have also been described [39]. Furthermore, in an acute campylobacteriosis model, vitamin D application could sufficiently dampen pro-inflammatory immune responses upon peroral infection of mice with the enteropathogen Campylobacter jejuni [34].…”

Antimicrobial and immune-modulatory effects of vitamin D provide promising antibiotics-independent approaches to tackle bacterial infections – lessons learnt from a literature survey

“…Previous reports documented health-beneficial effects of vitamins in general [4, 5, 6, 7, 8, 9, 10, 11, 12]. Among these, vitamin D has been shown to alleviate several morbidities, including bacterial infections caused by Mycobacterium tuberculosis and S. aureus [8, 18, 19, 20, 21, 22].…”

“…Previous reports documented health-beneficial effects of vitamins in general [4, 5, 6, 7, 8, 9, 10, 11, 12]. Among these, vitamin D has been shown to alleviate several morbidities, including bacterial infections caused by Mycobacterium tuberculosis and S. aureus [8, 18, 19, 20, 21, 22]. In addition, vitamin D has been shown to support clearance of P. aeruginosa by macrophages [8, 23] and to exert direct bactericidal activity against Helicobacter pylori [6, 7, 24], as well as against Streptococcus mutans [4].…”

“…Among these, vitamin D has been shown to alleviate several morbidities, including bacterial infections caused by Mycobacterium tuberculosis and S. aureus [8, 18, 19, 20, 21, 22]. In addition, vitamin D has been shown to support clearance of P. aeruginosa by macrophages [8, 23] and to exert direct bactericidal activity against Helicobacter pylori [6, 7, 24], as well as against Streptococcus mutans [4]. Notably, in vitro studies revealed that the expression of distinct virulence factors in Porphyromonas gingivalis , as well as bacterial growth, could be inhibited by vitamin D application [25].…”

Vitamin D3 Inhibits Helicobacter pylori Infection by Activating the VitD3/VDR-CAMP Pathway in Mice

“…Immune cells contain all the machinery required to synthesize and respond to VitD3, and this machinery is enhanced by challenge to the immune system (Gombart, 2009). Notably, VitD3 has been shown to support the clearance of Pseudomonas aeruginosa (P. aeruginosa) by use of macrophages (Nouari et al, 2016;Andrade et al, 2018) and to exert direct bactericidal activity against Streptococcus mutants (Saputo et al, 2018). In vitro studies have revealed that VitD3 application can inhibit virulence factor expression in Porphyromonas gingivalis and halt bacterial growth (Grenier et al, 2016).…”