Antibacterial Activity Of Antibiotics Research Articles

Itaconate induces tolerance of Staphylococcus aureus to aminoglycoside antibiotics.

Staphylococcus aureus is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of S. aureus, but research in this area has been limited. In this study,the minimum inhibitory concentration (MIC) of the antibiotics against S. aureus was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in S. aureus through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of S. aureus was evaluated by monitoring the growth of S. aureus in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in S. aureus when exposed to itaconate. According to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.

Phenotypic characterization and antibiotic resistance of enterobacteria strains isolated from samples of patients in the towns of Moundou and Sarh in Chad

Today, enterobacteria constitute one of the most predominant causes of nosocomial and acquired infections in our communities. The bactericidal action of antibiotics on bacteria is used therapeutically, unfortunately the latter have started to develop resistances. Antibiotic resistance remains a major global public health issue, a serious problem in some of the world's poorest countries such as Chad. The objective of this study is to identify the strains of enterobacteria coming from samples of patients admitted to the Moundou and Sarh health centers, and to report their resistance profiles. A total of 278 samples consisting of urine (133) and stools (145) were collected in the laboratories of the two provincial hospitals of Sarh and Moundou between September and December 2021. The samples were processed and analyzed according to standard microbiology methods. The study of the sensitivity of different strains of enterobacteria with 14 antibiotic disks was evaluated by the disk diffusion method in agar medium. A total of 278 samples (urine, stool) including 111 strains of Enterobacteria, including 55 strains of E. coli, Enterobacter spp (n=17), klebsiella (n=11), Salmonella (n=9), Serratia ( n=7), Citrobacter (n=6) and Shigella (n=2) were isolated in the laboratory in the towns of Moundou and Sarh in Chad. The antibiogram carried out on all isolated strains of enterobacteria expressed a resistance ranging between 33.3% and 83.3% to 3rd generation cephalosporins, 30.3% and 50.0% to aminoglycosides. On the other hand, a strain of Salmonella is resistant to imipenem in Sarh. This study shows a high level of resistance acquired to different families of antibiotics by our bacterial strains studied. This resistance highlights the need to adapt therapeutic regimens to local epidemiology. Keywords : Characterization, Phenotype, Antibiotic resistance, Enterobacteria, Cities, Chad

Cost-effective one-spot hydrothermal synthesis of graphene oxide nanoparticles for wastewater remediation: AI-enhanced approach for transition metal oxides

Outer ear infections (OEs) affect millions of people each year and are associated with significant medical costs.The usage of multiple antibiotics to treat ear contamination is a concern because it can have an environmental impact, especially on soil and water.The increased use of antibiotics has exposed bacterial ecosystems to high concentrations of antibiotic residues.Although there have been efforts to minimize the impact of antibiotics, adsorption methods have yielded better and more viable results, and carbon-based materials are effective for environmental remediation.Graphene oxide (GO) is a versatile material used in various applications such as nanocomposites, antibacterial agents, photocatalysis, electronics, and biomedicine.GO can act as an antibiotic carrier and affect the antibacterial efficacy of antibiotics.However, the processes responsible for the antibacterial activity of GO and antibiotics in treating ear infections are unknown.This study investigates the effect of GO on the antibacterial activity of tetracycline (TT) against Escherichia coli (E.coli)-negative bacteria.Artificial Neural Network-Genetic Algorithm (ANN-GA) was applied to analyze data on the effectiveness of different doses and combinations of graphene oxide and antibiotics in treating ear infections.This study could help identify the most effective treatment protocols and potentially reduce the risk of antibiotic resistance.The R-squared (R2) value, RMSE, and MSE all fall within the proper levels for fitting criteria, with R2 ≥ 0.97 (97%), RMSE ≤ 0.036064, and MSE ≤ 0.00199 (6% variance).The outcomes showed high antimicrobial activity, resulting in a 5-log decline of E.coli.In experiments, GO was shown to coat the bacteria, interfere with their cell membranes, and aid in the prevention of bacterial growth, although this effect was somewhat weaker for E.coli.The concentration and duration at which bare GO can kill E.coli are both important factors.The antibacterial activity of antibiotics can be either boosted or reduced by the presence of GO, depending on the GO's interaction with the antibiotic, the GO's contact with the microbe, and the sensitivity of the bacteria to the antibiotic.The antibacterial efficiency of the combination of GO and antibiotics varies depending on the specific antibiotic and microorganism being targeted.

High expression of antimicrobial peptides cathelicidin-BF in Pichia pastoris and verification of its activity.

Antibacterial peptides are endogenous polypeptides produced by multicellular organisms to protect the host against pathogenic microbes, they show broad spectrum antimicrobial activities against various microorganisms and possess low propensity for developing resistance. The purpose of this study is to develop recombinant antibacterial peptide cathelicidin-BF by genetic engineering and protein engineering technology, and study its antibacterial activity in vitro and in vivo, so as to provide reference for the production and application of recombinant antibacterial peptide cathelicidin-BF. In this study, on account of Pichia pastoris eukaryotic expression system, we expressed and prepared antibacterial peptide cathelicidin-BF. Then, the minimum inhibitory concentration of antibacterial peptide cathelicidin-BF and the comparison with the antibacterial activity of antibiotics were determined through the antibacterial experiment in vitro. Chickens as infection model were used to verify the antibacterial peptide activity in vivo. The results show that the bacteriostatic ability of antibacterial peptide cathelicidin-BF is similar to that of antibiotics in certain concentration, and can reach the treatment level of antibiotics. Although the mode of administration of antibacterial peptide is still limited, this study can provide reference for the future research of antibacterial peptide.

The Combination Effect of Curcumin on the Antibacterial Activity of Antibiotics

يعتبر ظهور البكتيريا المقاومة للأدوية المتعددة للمضادات الحيوية الشائعة وتزايدها السريع من المشاكل الصحية الرئيسية ؛ أصبحت العديد من المضادات الحيوية أقل فاعلية ضد البكتيريا المسببة للأمراض ، لذلك هناك حاجة ملحة للبحث عن مواد جديدة مضادة للبكتيريا خاصة من المصادر الطبيعية. أظهرت العديد من الدراسات أن الأعشاب قد تؤثر إيجابًا على قابلية الميكروبات للمضادات الحيوية. في هذه الدراسة تم دراسة التأثير المركب للكركمين مع الأموكسيسيلين ضد البكتيريا الممرضة المختلفة (S. aureus ، Streptococcus ، E. coli ، Pseudomonas ، و Proteus) باستخدام طريقة الانتشار الجيد. تشير النتائج إلى أن الكركمين له تأثير تآزري ، ومضاد ، ولامبالاة عند إضافته إلى تركيزات مختلفة من الأموكسيسيلين ضد البكتيريا المسببة للأمراض. كانت الاستجابة التآزرية 70٪ ، واللامبالاة 20٪ ، والعداء 10٪. أظهرت النتائج أن الكركمين يحسن التأثير المبيد للجراثيم للمضاد الحيوي وله إمكانات في العلاج المركب ضد البكتيريا المسببة للأمراض المختلفة.

Tetracycline-loaded magnesium oxide nanoparticles with a potential bactericidal action against multidrug-resistant bacteria: In vitro and in vivo evidence

Worldwide, the emergence of diarrhoea-causing multi-drug resistant (MDR) bacteria has become a crucial problem in everyday life. Tetracycline (TC) is a bacteriostatic agent that has a wide spectrum of antibacterial activity. One potential strategy to enhance the penetration and antibacterial activity of antibiotics is the use of nanotechnology. In this context, this study dealt with the synthesis of TC loading in biocompatible magnesium oxide nanoparticles (MgONPs), its characterization, and the potency of killing against diarrhoea-causing MDR bacteria E. coli and S. flexneri. TC loaded- MgONPs (MgONPs-TC) were characterized by DLS, SEM-EDS, UV–vis spectroscopy, and FTIR techniques with adequate physical properties. Antibacterial and antibiofilm studies indicate that this nanoparticle successfully eradicated both planktonic and sessile forms of those bacteria. It also significantly reduced the production of bacterial EPS, different levels of antioxidant enzymes, and induced reactive oxygen species (ROS) in the bacterial cell as a mode of antibacterial action. In particular, MgONPs-TC were efficient in reducing the colonization of MDR E. coli and S. flexneri in the C. elegans model. Therefore, all these data suggest that MgONPs-TC are a highly promising approach to combating diseases associated with diarrhoea-causing MDR bacteria in the medical field with limited health care budgets.

Potential secondary metabolite analysis of soil Streptomyces sp. GMR22 and antibacterial assay on Porphyromonas gingivalis ATCC 33277

Infectious diseases caused by oral pathogenic bacteria are currently a serious problem due to the increasing incidence of antimicrobial resistance. Streptomyces sp. GMR22, a soil actinobacterium which has large-genome size. In previous studies, it was known to have antifungal, and antibiofilm activity on Candida albicans. However, its antibacterial activity on oral pathogenic bacterium, Porphyromonas gingivalis is not clear. This study aimed to identify potential active compound based on genome mining analysis and to evaluate the antibacterial activity of GMR22 extract on P. gingivalis ATCC 33277. Potential active compounds and biosynthesis gene clusters were analysis using antiSMASH version 5. Antibacterial activity assay was carried out by the microdilution method on P. gingivalis ATCC 33277. Based on genome mining analysis polyketide synthase (PKS), the Streptomyces sp. GMR22 is the abundant BGCs (35%) and has large-predicted compounds which have antibiotic-antibacterial activity (22.9%). On antibacterial assay, chloroform extract of GMR22 at 7.8 – 62.5 µg/mL has high antibacterial activity on P. gingivalis compared to other extracts. Soil Streptomyces sp. GMR22 bacterium has biotechnological potential to produce active compounds for antibacterial.

Restoration of antibacterial activity of inactive antibiotics via combined treatment with a cyanographene/Ag nanohybrid

The number of antibiotic-resistant bacterial strains is increasing due to the excessive and inappropriate use of antibiotics, which are therefore becoming ineffective. Here, we report an effective way of enhancing and restoring the antibacterial activity of inactive antibiotics by applying them together with a cyanographene/Ag nanohybrid, a nanomaterial that is applied for the first time for restoring the antibacterial activity of antibiotics. The cyanographene/Ag nanohybrid was synthesized by chemical reduction of a precursor material in which silver cations are coordinated on a cyanographene sheet. The antibacterial efficiency of the combined treatment was evaluated by determining fractional inhibitory concentrations (FIC) for antibiotics with different modes of action (gentamicin, ceftazidime, ciprofloxacin, and colistin) against the strains Escherichia coli, Pseudomonas aeruginosa, and Enterobacter kobei with different resistance mechanisms. Synergistic and partial synergistic effects against multiresistant strains were demonstrated for all of these antibiotics except ciprofloxacin, which exhibited an additive effect. The lowest average FICs equal to 0.29 and 0.39 were obtained for colistin against E. kobei and for gentamicin against E. coli, respectively. More importantly, we have experimentally confirmed for the first time, that interaction between the antibiotic's mode of action and the mechanism of bacterial resistance strongly influenced the combined treatment’s efficacy.

A bioinspired hierarchical nanoplatform targeting and responding to intracellular pathogens to eradicate parasitic infections

Intracellular bacteria-mediated antibiotic tolerance, which acts as a “Trojan horse,” plays a critical and underappreciated role in chronic and recurrent infections. Failure of conventional antibiotic therapy is often encountered because infected cells prevent drug permeation or the drug concentration is too low at the site of resident bacteria. New paradigms are therefore urgently needed for intracellular anti-infective therapy. Here, a novel therapeutic was developed for targeted delivery of antibiotics into bacteria-infected macrophages to improve drug accumulation in intracellular niches and bactericidal activity of antibiotics against intracellular pathogens. This hierarchical nanoplatform includes a glycocalyx-mimicking shell that enables rapid uptake by macrophages. Subsequently, the targeting moieties are activated in response to the bacteria, and the release of entrapped antibiotics is triggered by bacteria and bacteria-secreted enzymes. The self-immolative drug delivery nanoplatform eliminates intracellular pathogenic bacteria residing in macrophages more efficiently compared to drugs alone. The in vivo dynamically monitored nanosystem also efficiently inhibited the growth of intracellular Staphylococcus aureus in infected muscles of mice with negligible systemic toxicity. The novel dual-targeting design of an all-in-one therapeutic platform can be used as an alternative strategy to reanimate antibiotic therapy against multifarious intracellular bacterial infections.

Antibiotic susceptibility of Staphylococcus aureus with different degrees of biofilm formation

Staphylococcus aureus is one of the most common pathogens in biofilm-associated chronic infections. S. aureus living within biofilms evades the host immune response and is more resistant to antibiotics than planktonic bacteria. In this study, we generated S. aureus with low and high levels of biofilm formation using the rbf (regulator of biofilm formation) gene and performed a BioTimer assay to determine the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of various types of antibiotics. We showed that biofilm formation by S. aureus had a greater effect on MBC than MIC, probably due to the different growth modes between planktonic and biofilm bacteria. Importantly, we found that the MBC for biofilm S. aureus was much higher than that for planktonic cells, but there was little difference in MBC between low and high levels of biofilm formation. These results suggest that once the biofilm is formed, the bactericidal activity of antibiotics is significantly reduced, regardless of the degree of S. aureus biofilm formation. We propose that S. aureus strains with varying degrees of biofilm formation may be useful for evaluating the anti-biofilm activity of antimicrobial agents and understanding antibiotic resistance mechanisms by biofilm development.

Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation.

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M−1 and enthalpy change values up to −4 kJ·M−1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.

Molecular characterization and antibacterial activity of oral antibiotics and copper nanoparticles against endodontic pathogens commonly related to health care-associated infections.

To carry out molecular characterization and determine the antibacterial activity of oral antibiotics and copper nanoparticles (Cu-NPs) against endodontic strains isolated from persistent infections. Root canal samples from 24 teeth in different patients with persistent endodontic infections were obtained. The isolated strains were identified by biochemical tests and 16S rDNA sequencing. Genotyping was achieved by molecular methods. The antibacterial activity of antibiotics and copper nanostructures was determined by using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Furthermore, a time-kill kinetics assay was evaluated. Nonparametric tests (Kruskal-Wallis ANOVA) were performed (p value <0.05). Twenty-one isolated strains were identified. Six isolates of Enterococcus faecalis were grouped into two clusters of three isolates each, two of which were clones. All were clarithromycin-resistant and erythromycin. Eight Pseudomonas putida presented two clusters, two Pseudomonas spp. were not clonal, and all were resistant to the tested antibiotics except tetracycline. Two of five strains of Cutibacterium acnes were clonal, and all were resistant only to metronidazole. The lowest MIC and MBC values were obtained with Cu-NPs. Time-kill kinetics using Cu-NPs showed a significant decrease in all tested species within 4 h and reached 100% in 2 h for C. acnes. In this study, in relation to health care-associated infections, endodontic strains of each species isolated at least in one patient were polyclonal. In Pseudomonas spp., at least one clone was shared between patients. E. faecalis and C. acnes strains were susceptible to low Cu-NP concentrations, while Pseudomonas spp. strains were resistant. Assessing and keeping track of the susceptibility of clinical strains to antimicrobial compounds is important for the clinical outcome. Based on our results, Cu-NPs could be an alternative for endodontic treatment, in order to avoid selection of resistant strains.

Green tea extract-mediated augmentation of imipenem antibacterial activity against Enterobacter cloacae clinical isolates

The emergence of pathogenic bacteria with β-lactam antibiotics-resistant profile has threatened the continued use of such antibiotics in the future. This research was conducted to investigate the antimicrobial activity of green tea ethanol extract (GTE) and its ability to improve the antibacterial action of several β-lactam antibiotics against Enterobacter cloacae clinical isolates. The simplicia of green tea was extracted by sonication for 30 minutes using 50% ethanol solvent, and the total phenolic content of the GTE was subsequently determined. Next, the GTE used in testing against two clinical isolates of E. cloacae was obtained from the Pathology Laboratory of Wahidin Sudiro Husodo Hospital in Makassar. The sensitivity of bacteria to GTE was confirmed using the agar diffusion method, the Vitek® rapid method, and the double-disk synergistic test. Antibacterial activity of antibiotics, GTE, and combination of antibiotics with GTE were then tested against clinical isolates of E. cloacae using the checkerboard microdilution assay. The results showed that GTE contained 51.64 ± 0.21 % measured as gallic acid equivalent and 37.95 + 5.17 % Epigallocatechin gallate (EGCG). The confirmatory test results indicated that one clinical isolate of E. cloacae (code 13/04) was resistant to amoxicillin-clavulanate but did not produce an extended-spectrum β-lactamase (ESBL). Another clinical E. cloacae isolate (code 275B/06) was indicated to produce ESBL and demonstrated to yield resistance to amoxicillin-clavulanate and cefotaxime. The minimum inhibitory concentration of GTE against the two clinical isolates of E. cloacae was &gt;8000 ppm (8 mg/ml). In conclusion, GTE could not increase the antibacterial activity of amoxicillin and cefotaxime, but it was sufficient to improve the activity of imipenem against the tested isolates of E. cloacae .

Galbofloxacin: a xenometal-antibiotic with potent in vitro and in vivo efficacy against S. aureus.

Siderophore-antibiotic drug conjugates are considered potent tools to deliver and potentiate the antibacterial activity of antibiotics, but only few have seen preclinical and clinical success. Here, we introduce the gallium(iii) complex of a ciprofloxacin-functionalized linear desferrichrome, Galbofloxacin, with a cleavable serine linker as a potent therapeutic for S. aureus bacterial infections. We employed characterization using in vitro inhibitory assays, radiochemical, tracer-based uptake and pharmacokinetic assessment of our lead compound, culminating in in vivo efficacy studies in a soft tissue model of infection. Galbofloxacin exhibits a minimum inhibitory concentration of (MIC98) 93 nM in wt S. aureus, exceeding the potency of the parent antibiotic ciprofloxacin (0.9 μM). Galbofloxacin is a protease substrate that can release the antibiotic payload in the bacterial cytoplasm. Radiochemical experiments with wt bacterial strains reveal that 67Galbofloxacin is taken up efficiently using siderophore mediated, active uptake. Biodistribution of 67Galbofloxacin in a mouse model of intramuscular S. aureus infection revealed renal clearance and enhanced uptake in infected muscle when compared to 67Ga-citrate, which showed no selectivity. A subsequent in vivo drug therapy study reveals efficient reduction in S. aureus infection burden and sustained survival with Galbofloxacin for 7 days. Ciprofloxacin had no treatment efficacy at identical molecular dose (9.3 μmol kg−1) and resulted in death of all study animals in <24 hours. Taken together, the favorable bacterial growth inhibitory, pharmacokinetic and in vivo efficacy properties qualify Galbofloxacin as the first rationally designed Ga-coordination complex for the management of S. aureus bacterial infections.

Role of Secondary Oxidative Stress in the Bactericidal Action of Antibiotics

Exposure to β-lactam, fluoroquinolone, and aminoglycoside antibiotics caused an increase in the production of hydrogen peroxide and the expression of OxyR-regulon of the oxidative stress response in Escherichia coli cells. Under the conditions of microaeration, the attenuation of secondary oxidative stress due to the addition of the antioxidant thiourea influenced the antibacterial effect of fluoroquinolones. Thiourea potentiated the effect of sublethal (not decreasing the number of colony-forming units below 103/mL) doses of the antibiotic and increased the viability of cells exposed to lethal doses. The addition of thiourea reduced the expression of OxyR-regulon activated by the sublethal action of the antibiotic to the level of antibiotic-free culture. When exposed to lethal doses, a decrease in the antibiotic-mediated expression of oxidative stress response genes in the presence of thiourea was also observed; however, the expression level remained higher compared to antibiotic-free culture. This may indicate the dual role of ROS under antibiotic treatment as the damaging agents contributing to cell death and as signal molecules activating stress responses.

Teicoplanin-loaded chitosan-PEO nanofibers for local antibiotic delivery and wound healing

Antibiotic-loaded nano-delivery systems offer an advanced approach to overcome several limitations associated with antibiotic therapy. Antibiotic-loaded nanofibers can be applied topically for skin and wound healing, post operation implants for the prevention of abdominal adhesion, and prophylaxis and treatment of infections in orthopedic surgery. Here, the authors report the development of local antibiotic delivery system using chitosan- polyethylene oxide (PEO) nanofibers for delivery of teicoplanin. Successful electrospinning of chitosan-PEO solution containing 2 and 4 w/v% teicoplanin resulted in uniform and bead-less nanofibers. Nanofibers were able to release teicoplanin up to 12 days. Antibacterial test in agar diffusion and time-kill study on Staphylococcus aureus also demonstrate that loading teicoplanin in chitosan-PEO nanofibers not only kept the antibacterial activity of antibiotic but also, enhanced it up to 1.5 to 2 fold. Teicoplanin loaded nanofibers did not show any cytotoxicity to human fibroblast. Moreover, in vivo study on rat full thickness wound model confirmed safety and efficacy of applying teicoplanin loaded nanofibers and significant improve in wound closure was observed especially with nanofibers containing 4% teicoplanin. The sustained release profile, enhanced drug activity, cytocompatibility, and significant wound healing activity affirm the potential applications of teicoplanin-loaded nanofibers in wound healing and local antibiotic delivery.

Microbial Sensor for Determination of Amoxicillin Activity

A sensor based on the electrodynamic microwave resonator has been developed to determine the antibacterial activity of antibiotics using amoxicillin as an example. Microbial cells immobilized on the polystyrene film surface were used as a sensitive element of the sensor. The optimal conditions for the immobilization of Escherichia coli Xl-1 microbial cells on the surface of a thin polystyrene film modified in high-frequency argon discharge plasma and deposited on a lithium niobate plate were determined. The effect of amoxicillin on immobilized microbial cells was studied using the developed sensor. It has been established that the increase in con- centration of amoxicillin from 5 to 50 μg/ml leads to a significant change in the reflection coefficient S11 at the resonance frequency from the lithium niobate plate in the range of -12.6 dB — -15.1 dB. It has been shown that the developed sensor allows determining the antibacterial activity of drugs in the studied concentration range with an analysis time of 15 min.

Effect of the lantibiotic nisin on inhibitory and bactericidal activities of antibiotics used against vancomycin-resistant enterococci

ObjectivesAntibiotic resistance is a serious issue facing clinicians all over the world. Vancomycin-resistant enterococci (VRE) are amongst the most common resistant pathogens that are isolated from patients suffering from infections in our locality. New antimicrobial agents such as the lantibiotic nisin have been previously examined against resistant bacteria as it has strong antibacterial action with no chance of resistance development. This study aimed to explore the effect of nisin in combination with the conventional antibiotics against VRE, with a view to using it as an auxiliary therapy with such antibiotics for combating resistant isolates. MethodsTwenty-three VRE had been examined for the combined effect of nisin with the routine sets of antibiotics using the microplate dilution technique for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) testing. Checkerboard microbroth assay was conducted for inspection of synergism between nisin and either ampicillin or chloramphenicol. ResultsAn obvious improvement of inhibitory and bactericidal activities of the tested antibiotics after addition of lantibiotic nisin was observed, with a remarkable reduction in the MIC values of vancomycin against all of the isolates. Nisin recorded a synergistic outcome when combined with either ampicillin or chloramphenicol using the checkerboard assay. ConclusionNisin could be effectively considered as a supplementary agent to traditional antibiotics in the management of VRE-associated infections, as it had a synergistic outcome with commonly prescribed antibiotics such as ampicillin and chloramphenicol.

What Can Go Wrong When Applying Immune Modulation Therapies to Target Persistent Bacterial Infections.

Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity. Often, the causative agents of persistent infections are not drug-resistant species. Instead, bacterial persister cells temporarily enter a physiological state that is refractory to different classes of antibiotics. Supplemental therapies that potentiate antibiotic bactericidal efficiency and/or immune clearance of persistent pathogenic species may greatly improve the outcome of infectious disease. Here, we discuss the various outcomes in experimental studies in which a mega-dose of the energy-boosting vitamin B3 (nicotinamide) was applied in murine models of chronic infection to stimulate immune clearance of chronic infection or as an immune prophylactic treatment against the highly infectious pathogen, Burkholderia pseudomallei. It is our intent to raise awareness of the risks associated with immune modulation therapies. There is great variance in host immune responses to pathogenic bacteria. Each immune modulation approach needs to be tailored to a well-characterized host-pathogen interaction.

Synergistic antibacterial actions of graphene oxide and antibiotics towards bacteria and the toxicological effects of graphene oxide on human epidermal keratinocytes

Graphene oxide (GO) has displayed antibacterial activity that has been investigated in the past, however, information on synergistic activity of GO with conventional antibiotics is still lacking. The objectives of the study were to determine the combinatorial actions of GO and antibiotics against Gram-positive and Gram-negative bacteria and the toxicological effects of GO towards human epidermal keratinocytes (HaCaT). Interactions at molecular level between GO and antibiotics were analyzed using Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Changes in the antibacterial activity of antibiotics towards bacteria through the addition of GO was investigated. Toxicity of GO towards HaCaT cells were examined as skin cells play a role as the first line of defense of the human body. The ATR-FTIR characterizations of GO and antibiotics showed adsorption of tested antibiotics onto GO. The combinatorial antibacterial activity of GO and antibiotics were found to increase when compared to GO or antibiotic alone. This was attributed to the ability of GO to disrupt bacterial membrane to allow for better adsorption of antibiotics. Cytotoxicity of GO was found to be dose-dependent towards HaCaT cell line, it is found to impose negligible toxic effects against the skin cells at concentration below 100 μg/mL.