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. 2019 Sep 9;26(1):69.
doi: 10.1186/s12929-019-0561-6.

Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria

Hala A Farrag  1 , Nagwa Abdallah  2 , Mona M K Shehata  3 , Ebthag M Awad  1
Affiliations
Free PMC article

Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria

Hala A Farrag et al. J Biomed Sci. .
Free PMC article

Abstract

Background: This study sought to develop new strategies for reverting the resistance of pathogenic Gram-negative bacilli by a combination of conventional antibiotics, potent permeabilizers and natural beta lactamase inhibitors enhancing the activity of various antibiotics.

Methods: The antibiotic susceptibility in the presence of natural non-antibacterial tested concentrations of phytochemicals (permeabilizers and natural beta lactamase inhibitors) was performed by disk diffusion and susceptibility assays. Thymol and gallic acid were the most potent permeabilizers and facilitated the passage of the antibiotics through the outer membrane, as evidenced by their ability to cause LPS release, sensitize bacteria to SDS and Triton X-100.

Results: The combination of permeabilizers and natural beta lactamase inhibitors (quercetin and epigallocatechin gallate) with antibiotics induced greater susceptibility of resistant isolates compared to antibiotic treatment with beta lactamase inhibitors alone. Pronounced effects were detected with 24.4 Gy in vitro gamma irradiation on permeability barrier, beta lactamase activity, and outer membrane protein profiles of the tested isolates.

Conclusions: The synergistic effects of the studied natural phytochemicals and antibiotics leads to new clinical choices via outer membrane destabilization (permeabilizers) and/or inactivation of the beta lactamase enzyme, which enables the use of older, more cost-effective antibiotics against resistant strains.

Keywords: Beta lactam resistance; In vitro gamma irradiation; Natural beta lactamase inhibitors; Outer membrane permeability; Pathogenic gram-negative bacilli; Permeabilizers.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
SDS-PAGE of Proteinase K-treated cell-free supernatants of Escherichia coli3 (silver staining). Lanes: 1, untreated (control); 2, irradiated supernatant; 3, thymol supernatant; 4, gallic acid supernatant; 5, EDTA supernatant; 6, chitosan supernatant
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