Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria

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.

Multidrug Resistant Acinetobacter baumannii Biofilms: Evaluation of Phenotypic–Genotypic Association and Susceptibility to Cinnamic and Gallic Acids

“…Nonetheless, as far as we know, scarce data are available about its antimicrobial activity against MDR A. baumannii. Gallic acid is a phenolic acid with reported antibacterial activity, especially in combination with conventional antibiotics ( Shao et al, 2015 ; Dos Santos et al, 2018 ; Farrag et al, 2019 ). Notably, the mean minimal effective dose of cinnamic acid (1.2 mg/ml) was significantly lower than that of gallic acid (1.67 mg/ml).…”

A Novel Weissella cibaria Strain UTNGt21O Isolated from Wild Solanum quitoense Fruit: Genome Sequence and Characterization of a Peptide with Highly Inhibitory Potential toward Gram-Negative Bacteria

“…No significant dose response was detected in case of E. coli, while with Salmonella cells a dose dependent response was detected, suggesting that with the increase of the peptide concentration the membrane destabilized increasing its permeability. When Salmonella cells were treated with 2× MIC peptide and the ONP release was monitored over time (30,60,80, 100, and 120 min), we observed that the steady-state level of β-galactosidase was recorded at 60 min and remained constant while in case of E. coli the steady state level was reached at 100 min (data not shown). However, the increase of cytoplasmic membrane permeabilization may correlate with the membrane disruption, leading to leakage of cell cytoplasmic content and cell death.…”

“…After the complete genome was assembled, BLAST analysis was carried out to identify to which species each scaffold showed similarity. Out of 31 contigs analyzed 20 contigs hits matched the core genome of different groups within Weissella and for 11 contigs (15,17,21,23,24,(26)(27)(28)(29)(30)(31) no match was shown in database ( Table S4). The largest contig 1 of the subject query (UTNGt21O) hits W. cibaria genome with an 83 percentage of identity with no gaps (0).…”

“…Natural antimicrobial peptides that inhibit the growth of pathogenic bacteria could be a suitable alternative to disinfectant solutions that are only meant to kill rapidly, but this feature is not maintained throughout time, such as conservation during storage [30]. In this study, to identify the effect of the peptide UTNGt21O on cell viability, different doses were added to Salmonella enterica subsp.…”

Phage-Encoded Endolysins

“…In Gram-negative bacteria, the peptidoglycan layer (susceptible layer) is protected by a less permeable outer membrane. Various strategies have been adopted to address this issue, including the use of outer membrane permeabilizers such as EDTA, gallic acid, and thymol in combination with endolysins in Gram-negative bacteria to provide significant results [ 169 ]. permeablilizer…”