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.

Background The colibactin and cytotoxic necrotizing factor 1 (Cnf 1) are toxins with cell cycle modulating effects that contribute to tumorgenesis and hyperproliferation. This study aimed to investigate the prevalence and pathologic effects of Cnf 1 and colibactin among hemolytic uropathogenic Escherichia coli ( UPEC ). The bioinformatics approach incorporated in this study aimed to expand the domain of the in vitro study and explore the prevalence of both toxins among other bacterial species. A total of 125 E. coli isolates were recovered from UTIs patients. The isolates were tested for their hemolytic activity, subjected to tissue culture and PCR assays to detect the phenotypic and genotypic features of both toxins. A rat ascending UTI in vivo model was conducted using isolates expressing or non-expressing Cnf 1 and colibactin (ClbA and ClbQ). The bioinformatics analyses were inferred by Maximum likelihood method and the evolutionary relatedness was deduced by MEGA X. Results Only 21 (16.8%) out of 125 isolates were hemolytic and 10 of these (47.62%) harbored the toxins encoding genes ( cnf 1 + , clbA + and clbQ + ). The phenotypic features of both toxins were exhibited by only 7 of the ( cnf 1 + clbA + clbQ + ) harboring isolates. The severest infections, hyperplastic and genotoxic changes in kidneys and bladders were observed in rats infected with the cnf 1 + clbA + clbQ + isolates. Conclusion Only 33.3% of the hemolytic UPEC isolates exhibited the phenotypic and genotypic features of Cnf 1 and Colibactin. The in vivo animal model results gives an evidence of active Cnf 1 and Colibactin expression and indicates the risks associated with recurrent and chronic UTIs caused by UPEC . The bioinformatics analyses confirmed the predominance of colibactin pks island among Enterobacteriaceae family (92.86%), with the highest occurrence among Escherichia species (53.57%), followed by Klebsiella (28.57%), Citrobacter (7.14%), and Enterobacter species (3.57%). The Cnf 1 is predominant among Escherichia coli (94.05%) and sporadically found among Shigella species (1.08%), Salmonella enterica (0.54%), Yersinia pseudotuberculosis (1.08%), Photobacterium (1.08%), Moritella viscosa (0.54%), and ...

BackgroundLife-threatening central venous catheter-related infections are primarily initiated by biofilm formation on the catheter surface. Antibiotic lock therapy is recommended for eradicating intraluminal biofilm. In the era of antibiotic resistance, antibiotics of natural origins provide an effective and cheap option for combating resistant strains. Garlic especially stole the spotlight because of its impressive antimicrobial effectiveness against such superbugs.AimIs to estimate the potential use of fresh garlic extract (FGE) as a lock agent against multi-drug resistant (MDR) bacteria.MethodsThe agar well diffusion and broth microdilution techniques were employed to test the antimicrobial activities of FGE against five MDR strains; E. coli, Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Serratia marscens (S. marscens) and Methicillin-resistant Staphylococcus aureus (MRSA). Then the protective and therapeutic efficiencies of FGE against bacterial biofilms were in-vitro evaluated; at concentrations of 100, 75, 50 and 25%; in tissue culture plate (TCP) and on the polyurethane (PU) sheets using the crystal violet (CV) assay and colony-forming unit (CFU), respectively. Scanning electron microscopy (SEM) was also used to confirm eradication of biofilms on PU sheets. Finally, systemic and deep tissue infections by P. aeruginosa and MRSA were induced in mice that were then treated by FGE at either 100 or 200 mg/kg for seven days. Where the antibacterial activity was assessed by tissue and blood culturing at the end of the treatment period. Biochemical, hematological and histological parameters were also investigated.ResultsFGE exhibited potent in-vitro and in-vivo antibacterial and antibiofilm activities against MDR strains. It not only didn’t exhibit toxicological effects at the hematological and the histological levels but also provided protective effects as demonstrated by the significant drop in the biochemical parameters.ConclusionFGE has the potential to be used as a prophylactic and/or therapeutic lock agent against biofilm-associated infections caused by MDR bacteria.

In the era of antibiotic resistance, antimicrobial polymers represent state of the art innovation evolved to fight biofilm-associated infections. In the present study, novel self-disinfecting polyurethane (PU) catheter materials were developed. Gamma radiation-induced graft copolymerization was used to functionalize PU using acrylic acid-co-glycidyl methacrylate (AAc/GMA) binary comonomer. The grafted PU, PU-g-(AAc-co-GMA), was subsequently modified by covalent immobilization of cefepime and/or wet in-situ intermatrix synthesis of ZnO (NPs) to produce PU-g-(AAc-co-GMA)/cefepime, PU-g-(AA-co-GMA-cefepime/ZnO and PU-g-(AAc-co-GMA)/ZnO nanocomposites, respectively. Modified polymers were characterized by Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and scanning electron microscope (SEM). Finally, the antibacterial and antibiofilm characteristics were evaluated against five multidrug-resistant (MDR) clinical bacterial isolates; including Gram-positive and Gram-negative microorganisms. FTIR confirmed the successful grafting and subsequent immobilization of cefepime. Formation of ZnO was verified by EDX analysis, while XRD analysis revealed the crystalline nature of ZnO NPs with a size range of 43-62 nm. Moreover, SEM showed the morphology, particle size and distribution of ZnO NPs within the prepared nanocomposites. The modified PU catheter nancomposites with or without cefepime showed excellent antibacterial and anti-biofilm characteristics. The prepared polymeric biocides could be potential candidates in medical care to combat biofilm formation on biomaterials.

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