Comparative meta-analysis of antimicrobial resistance from different food sources along with one health approach in the Egypt and UK.

BACKGROUND: Antimicrobial resistance (AMR) is a critical global issue that poses significant threats to human health, animal welfare, and the environment. With the increasing emergence of resistant microorganisms, the effectiveness of current antimicrobial medicines against common infections is diminishing. This study aims to conduct a competitive meta-analysis of surveillance data on resistant microorganisms and their antimicrobial resistance patterns in two countries, Egypt and the United Kingdom (UK). METHODS: Data for this study were obtained from published reports spanning the period from 2013 to 2022. In Egypt and the UK, a total of 9,751 and 10,602 food samples were analyzed, respectively. Among these samples, 3,205 (32.87%) in Egypt and 4,447 (41.94%) in the UK were found to contain AMR bacteria. RESULTS: In Egypt, the predominant resistance was observed against ß-lactam and aminoglycosides, while in the United Kingdom, most isolates exhibited resistance to tetracycline and ß-lactam. The findings from the analysis underscore the increasing prevalence of AMR in certain microorganisms, raising concerns about the development of multidrug resistance. CONCLUSION: This meta-analysis sheds light on the escalating AMR problem associated with certain microorganisms that pose a higher risk of multidrug resistance development. The significance of implementing One Health AMR surveillance is emphasized to bridge knowledge gaps and facilitate accurate AMR risk assessments, ensuring consumer safety. Urgent actions are needed on a global scale to combat AMR and preserve the effectiveness of antimicrobial treatments for the well-being of all living beings.

Determination of Antioxidants by DPPH Radical Scavenging Activity and Quantitative Phytochemical Analysis of Ficus religiosa.

The use of F. religiosa might be beneficial in inflammatory illnesses and can be used for a variety of health conditions. In this article, we studied the identification of antioxidants using (DPPH) 2,2-Diphenyl-1-picrylhydrazylradical scavenging activity in Ficus religiosa, as F. religiosa is an important herbal plant, and every part of it has various medicinal properties such as antibacterial properties that can be used by the researchers in the development and design of various new drugs. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) is a popular, quick, easy, and affordable approach for the measurement of antioxidant properties that includes the use of the free radicals used for assessing the potential of substances to serve as hydrogen providers or free-radical scavengers (FRS). The technique of DPPH testing is associated with the elimination of DPPH, which would be a stabilized free radical. The free-radical DPPH interacts with an odd electron to yield a strong absorbance at 517 nm, i.e., a purple hue. An FRS antioxidant, for example, reacts to DPPH to form DPPHH, which has a lower absorbance than DPPH because of the lower amount of hydrogen. It is radical in comparison to the DPPH-H form, because it causes decolorization, or a yellow hue, as the number of electrons absorbed increases. Decolorization affects the lowering capacity significantly. As soon as the DPPH solutions are combined with the hydrogen atom source, the lower state of diphenylpicrylhydrazine is formed, shedding its violet color. To explain the processes behind the DPPH tests, as well as their applicability to Ficus religiosa (F. religiosa) in the manufacture of metal oxide nanoparticles, in particular MgO, and their influence on antioxidants, a specimen from the test was chosen for further study. According to our findings, F. religiosa has antioxidant qualities and may be useful in the treatment of disorders caused by free radicals.

Quaternary Lipophilic Chitosan and Gelatin Cross-Linked Antibacterial Hydrogel Effectively Kills Multidrug-Resistant Bacteria with Minimal Toxicity toward Mammalian Cells.

Wounds or tissue openings in the skin are susceptible to bacterial attack, which can deteriorate and slow down the healing process. In this regard, antimicrobial gels are valuable as they mitigate the infection spread and assist in the healing. Despite the success, commercially available release-active antimicrobial gels suffer from narrow-spectrum activity, resistance induction, reservoir exhaustion, and in some cases may be associated with toxicity. To circumvent these limitations, herein, we have developed new quaternary lipophilic chitosan derivatives (QuaChi) synthesized by modifying the primary alcohol of the sugar moieties without altering the free amino groups of glucosamines. Compared to protonated chitosan, the synthesized derivatives exhibited improved water solubility and enhanced antibacterial activity against multidrug-resistant Gram-positive and Gram-negative bacteria including clinical isolates. The enhanced antibacterial activity was evident from the bacterial membrane depolarization leading to rapid inactivation of ∼105-106 bacterial cells within 2 h. The applicability of the chitosan derivatives was further demonstrated by developing antibacterial hydrogels by cross-linking the free amino groups of QuaChi with biocompatible gelatin through amide linkages. The hydrogel showed ∼5-7 log reduction of various multidrug-resistant bacteria including the stationary-phase cells within 6 h. Scanning electron microscopy revealed the loss of integrity of the bacterial structure when treated with the hydrogel, whereas mammalian cells (human embryonic kidney-293 (HEK-293)), when exposed to the hydrogel, appeared to be healthy with retained morphology. Collectively, these findings suggest that the developed hydrogel formulation can find potential applications to combat notorious drug-resistant bacterial infections in the healthcare settings.

Nanonization of a chemically synthesized flavone HMDF (3-hydroxy-3',4'-methylenedioxyflavone) by entrapping within calcium phosphate nanoparticles and exploring its antioxidant role on neural cellsin vitroand zebrafishin vivo.

The chemical synthesis of 3-hydroxy-3',4'-methylenedioxyflavone (HMDF) was reported to generate a modified flavone of potent antioxidant activity with significant neuropharmacological properties. In this study, HMDF was nanonized by entrapping within calcium phosphate nanoparticles (CPNPs). HMDF-CPNPs were of (i) size 25 nm, (ii) zeta potential (-) [22 ± 3] mV and (iii) entrapment efficiency 67%. HMDF-CPNPs, but not HMDF alone, inhibited thein vitroactivity of acetylcholinesterase enzymes to break down the major neurotransmitter compound acetylcholine. Moreover, nanonized HMDF had more antioxidant activity than bulk HMDF, as observed from its ability to protect mouse neural (N2A) cells from oxidative damage caused by H2O2exposure at the levels of cell viability, intracellular reactive oxygen species, mitochondrial membrane potential, cell cycle stages, nuclear integrity and neural connectivity. Anin vivostudy on zebrafish larvae (Denio rerio) also demonstrated that H2O2-mediated larval death was checked by HMDF-CPNP treatment. These results, therefore, suggest that HMDF-CPNPs may be developed as a potential antioxidant, particularly as a neuroprotectant.

Nanonized tetracycline cures deadly diarrheal disease 'shigellosis' in mice, caused by multidrug-resistant Shigella flexneri 2a bacterial infection.

We reported earlier about nano-formulation of tetracycline through its entrapment within calcium-phosphate nano-particle (CPNP) and about killing of pathogenic bacterium Shigella flexnari 2a, resistant to tetracycline (and 9 other antibiotics), by the nanonized antibiotic (Tet-CPNP). Here, we report on therapeutic role of Tet-CPNP against deadly diarrheal disease 'shigellosis' in mice, caused by Shigella infection. Our findings revealed that occurrence of mushy-stool excretion, colon-length shortening, weight-loss and bacterial colonization in gastrointestinal tract of mice due to shigellosis was significantly reduced by Tet-CPNP treatment. Histo- and immuno-logical studies showed that changes in morphology and level of inflammatory cytokines TNF-α, IL-1ß and IFN-γ in intestinal tissue of Shigella-infected mice were reverted to almost normal features by Tet-CPNP treatment. Bulk tetracycline had no anti-shigellosis action. Thus, nanonization of tetracycline rejuvenated the old, cheap, broad-spectrum antibiotic from obsolescence (due to resistance generation), making it highly beneficial for diarrhea-prone developing countries with limited health-care budgets.

Study of arsenic (III) removal by monolayer protected silver nanoadsorbent and its execution on prokaryotic system.

This work deals with the removal of arsenic by nanoadsorbent from aqueous environment that is subsequently applied to the biological system for the evaluation of its efficiency. We started our aspiration by the modification of carboxylate functionalized silver nanoparticle (nanoadsorbent) fabrication process. Batch mode arsenic uptake study by the nanoadsorbent was conducted considering several altering parameters and the reactants in addition to products were evaluated by several analytical techniques for the interpretation of the interaction mechanism. It was found nanoadsorbent, Ag@MSA is an efficient system for the exclusion of arsenic (III) from the aqueous system and due to the alteration in the ratio of silver content and protective agent, the characteristic profile of silver nanoparticles with an average diameter of 15 nm also became changed in respect of reported results. Here the low pH range (4-6) favors the interaction between nanoparticle and arsenic and it was found that the interaction was chemical in nature through adsorption or complex formation with surface carboxylate groups of the protecting agent (MSA). Following the interaction, a successful removal of arsenic (III) was achieved at a percentage of 94.16 with an initial concentration of 45 mg/L and equilibrium time of 60 min. Hence nanoparticles were executed against the toxic effect of arsenic in E. coli, an important gut microbe of higher animals, for the restoration of bacterial growth in arsenic pre-removed media. In this context the validation of this removal efficiency against arsenic induced toxicity was proved through several morphological studies, degree of oxidative damages and other biochemical attributes.

A simple robust method of synthesis of copper-silver core-shell nano-particle: evaluation of its structural and chemical properties with anticancer potency.

A simple method of synthesis of a stable bimetallic copper-silver nano-particle (CuAg-NP) was developed by successive reduction of Cu(NO3)2 and AgNO3, using hydrazine hydrate as the reducing agent and gelatin and poly-vinyl pyrrolidone (PVP) as the capping agents. The round-shaped particles were of a core-shell structure with a core of Cu0 atoms surrounded by a shell of Ag0 atoms. The size and the mol. wt. of the NPs were (100 ± 10) nm and (820 ± 157) Kd, respectively; the particles were crystalline in nature and 90% of the precursors Cu(NO3)2 and AgNO3 were converted to the NPs. The particles were more toxic to cancer cells than normal cells; the dose of the NPs (4-5 µg ml-1), that killed about 75% of the different human cancer cell lines viz, HepG2 (liver cancer), A549 (lung cancer) and AGS (stomach cancer), killed only about 22.5% of the normal cell lines viz, WRL68 (liver) and WI38 (lung). Therefore, the NP may be developed as a potent anticancer drug in future. The more detailed study on the cytotoxicity of the CuAg-NP on the HepG2 cell line revealed that the particles caused cell cycle arrest in a G2/M phase, depolarization of mitochondrial membrane potential, translocation of phosphatidylserine residues from inner to outer leaflets of cell membrane and DNA degradation; these phenomena confirmed that the NP-induced cell death was apoptotic in nature.

Tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP): Rejuvenation of an obsolete antibiotic to further action.

BACKGROUND: Increasing resistance in bacteria towards antibiotics has made it imperative to research on their revitalization to combat infectious diseases. This study dealt with synthesis of a nano-form of the antibiotic tetracycline, its characterization and potency of killing different multi-drug resistant diarrhea-causing bacteria. METHODS: Nano-formulation was done by loading tetracycline within biocompatible calcium phosphate nanoparticle. The synthesized tetracycline-loaded calcium phosphate nanoparticle (Tet-CPNP) was characterized by the techniques like TEM, DLS, EDS, FTIR, spectrofluorimetry and dialysis. Bactericidal activity of nano-particulate tetracycline was investigated by agar plating, spectrophotometry, phase contrast-fluorescence-atomic force microscopy and flow cytometry techniques. RESULTS: The Tet-CPNPs were 8±5nm in size and nearly spherical in shape, efficiency of tetracycline loading in CPNP was about 20% and the release of antibiotic from Tet-CPNPs was sustainable during 7days. Minimum inhibitory concentration (MIC) of Tet-CPNP on multiple antibiotic (including tetracycline) resistant bacteria like Escherichia coli, Salmonella kentuckey and Shigella flexneri was in the range of 20-40µg/ml, whereas MIC of free tetracycline was in the range of 150-180µg/ml. NP-mediated cell filamentation and cell membrane disintegration caused cell killing. Moreover, death of Shigella-infected Zebra fish larvae was stalled by Tet-CPNP treatment. CPNP itself had no toxic effect on bacteria as well as on Zebra fish. CONCLUSION: Our nano-formulation of tetracycline might reclaim a nearly obsolete antibiotic to further potential function. GENERAL SIGNIFICANCE: Such a study on revival of an old, cheap, broad-spectrum antibiotic to further action is highly beneficial to developing countries with limited health care budgets.

Peptide-Based Polymer-Polyoxometalate Supramolecular Structure with a Differed Antimicrobial Mechanism.

Because of the increasing prevalence of multidrug resistance feature, several investigations have been so far reported regarding the antibiotic alternative supramolecular bioactive agents made of hybrid assemblies. In this regard, it is well-established that combinational therapy inherited by assembled supramolecular structures can improve the bioactivity to some extent, but their mode of action has not been studied in detail. We provide first direct evidence that the improved mechanism of action of antimicrobial supra-amphiphilic nanocomposites differs largely from their parent antimicrobial peptide-based polymers. For the construction of a hybrid combinational system, we have synthesized side-chain peptide-based antimicrobial polymers via RAFT polymerization and exploited their cationic nature to decorate supra-amphiphilic nanocomposites via interaction with anionic polyoxometalates. Because of cooperative antimicrobial properties of both the polymer and polyoxometalate, the nanocomposites show an enhanced antimicrobial activity with a different antimicrobial mechanism. The cationic stimuli-responsive peptide-based polymers attack bacteria via membrane disruption mechanism, whereas free radical-mediated cell damage is the likely mechanism of polymer-polyoxometalate-based supra-amphiphilic nanocomposites. Thus, our study highlights the different antimicrobial mechanism of combinational systems in detail, which improves our understanding of enhanced antimicrobial efficacy.

Nanocarrier-mediated probiotic delivery: a systematic meta-analysis assessing the biological effects.

Probiotics have gained a significant attention as a promising way to improve gut health and overall well-being. The increasing recognition of the potential health advantages associated with functional food products, leading to a specific emphasis on co-encapsulating probiotic bacteria and bioactive compounds within a unified matrix. To further explore this concept, a meta-analysis was performed to assess the effects of probiotics encapsulated in nanoparticles. A comprehensive meta-analysis was conducted, encompassing 10 papers published from 2017 to 2022, focusing on the encapsulation of probiotics within nanoparticles and their viability in various gastrointestinal conditions. The selection of these papers was based on their direct relevance to the research topic. Random-effect models were used to aggregate study-specific risk estimates. In the majority of studies, it was observed that nano-encapsulated nanoparticles showed improved viability over time compared to their free state counterparts. At various time intervals, the odds ratios (OR) with 95% confidence intervals (CI) were estimated using fixed and random effect models. At 0 min, the OR (95%CI) was 2.79 (2.79; 2.80) and 2.38 (2.14; 2.64) for. At 30 and 60 min observation was at similar rate of 2.23 (2.23; 2.24) and 2.05 (1.73; 2.43). However, at 90 min it was 1.39 (1.39; 1.39) and 1.66 (1.29; 2.14) and at 120 min 2.41 (2.41; 2.42) and 2.03 (1.63; 2.52). Overall evaluation of encapsulation revealed an improvement in probiotic bacterial viability in simulated the gastrointestinal environments.

The Role of Animal-Assisted Therapy in Enhancing Patients' Well-Being: Systematic Study of the Qualitative and Quantitative Evidence.

Background: Animal-assisted therapy, also known as pet therapy, is a therapeutic intervention that involves animals to enhance the well-being of individuals across various populations and settings. Objective: This systematic study aims to assess the outcomes of animal-assisted therapy interventions and explore the associated policies. Methods: A total of 16 papers published between 2015 and 2023 were selected for analysis. These papers were chosen based on their relevance to the research topic of animal-assisted therapy and their availability in scholarly databases. Thematic synthesis and meta-analysis were used to synthesize the qualitative and quantitative data extracted from the selected papers. Results: The analysis included 16 studies that met the inclusion criteria and were deemed to be of moderate or higher quality. Among these studies, 4 demonstrated positive results for therapeutic mediation and one for supportive mediation in psychiatric disorders. Additionally, all studies showed positive outcomes for depression and neurological disorders. Regarding stress and anxiety, 3 studies indicated supportive mediation, while 2 studies showed activating mediation. Conclusions: The overall assessment of animal-assisted therapy shows promise as an effective intervention in promoting well-being among diverse populations. Further research and the establishment of standardized outcome assessment measures and comprehensive policies are essential for advancing the field and maximizing the benefits of animal-assisted therapy.

Functionalized chitosan based antibacterial hydrogel sealant for simultaneous infection eradication and tissue closure in ocular injuries.

Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)­silver chloride nanocomposites (QAm1-Agx) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by ∼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed ∼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds.

Polyoxometalate-Polymer Directed Macromolecular Architectonics of Silver Nanoparticles as Effective Antimicrobials.

A novel inorganic-organic-inorganic ternary bioactive material formulated on antimicrobial peptide-based polymer has been reported. Supramolecular approach has been employed to incorporate molecularly crowded tyrosine-based polymer stabilized silver nanoparticles into membrane bound vesicles exploiting polyoxometalate-triggered surface templating strategy. Utilizing the covalent reversible addition fragmentation chain transfer (RAFT) polymerization and exploiting templated supramolecular architectonics at biopolymer interface, the bioactive ternary polymeric nanohybrids have been designed against Shigellosis leveraging the antibacterial activities of silver nanoparticle, cationic amphiphilic tyrosine polymer and inorganic polyoxometalate. The detail investigation against Shigella flexneri 2a cell line demonstrates that the collaborative mechanism of the ternary hybrid composite enhances the bactericidal activity in comparison to only polyoxometalate and polymer stabilized silver nanoparticle with an altered mechanism of action which is established via detailed biological analysis.

Multifunctional Suture Coating for Combating Surgical Site Infections and Mitigating Associated Complications.

Despite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited ∼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes.

Antimicrobial nanocomposite coatings for rapid intervention against catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs) pose a significant challenge in hospital settings. Current solutions available on the market involve incorporating antimicrobials and antiseptics into catheters. However, challenges such as uncontrolled release leading to undesirable toxicity, as well as the prevalence of antimicrobial resistance reduce the effectiveness of these solutions. Additionally, conventional antibiotics fail to effectively eradicate entrenched bacteria and metabolically suppressed bacteria present in the biofilm, necessitating the exploration of alternative strategies. Here, we introduce a novel polymer-nanocomposite coating that imparts rapid antimicrobial and anti-biofilm properties to coated urinary catheters. We have coated silicone-based urinary catheters with an organo-soluble antimicrobial polymer nanocomposite (APN), containing hydrophobic quaternized polyethyleneimine and zinc oxide nanoparticles, in a single step coating process. The coated surfaces exhibited rapid eradication of drug-resistant bacteria within 10-15 min, including E. coli, K. pneumoniae, MRSA, and S. epidermidis, as well as drug-resistant C. albicans fungi. APN coated catheters exhibited potent bactericidal activity against uropathogenic strains of E. coli, even when incubated in human urine. Furthermore, the stability of the coating and retention of antimicrobial activity was validated even after multiple washes. More importantly, this coating deterred biofilm formation on the catheter surface, and displayed rapid inactivation of metabolically repressed stationary phase and persister cells. The ability of the coated surfaces to disrupt bacterial membranes and induce the generation of intracellular reactive oxygen species (ROS) was assessed through different techniques, such as electron microscopy imaging, flow cytometry as well as fluorescence spectroscopy and microscopy. The surface coatings were found to be biocompatible in an in vivo mice model. Our simple one-step coating approach for catheters holds significant potential owing to its ability to tackle multidrug resistant bacteria and fungi, and the challenge of biofilm formation. This work brings us one step closer to enhancing patient care and safety in hospitals.

Subretinal hyporeflective globule: A novel OCT finding in central serous chorioretinopathy.

PURPOSE: To describe the subretinal hyporeflective globule in cases of central serous chorioretinopathy (CSC). METHODS: A retrospective analysis of consecutive cases of CSC presenting to a tertiary eye care center in eastern India was conducted. Subretinal hyporeflective globules were identified as small globular lesions below the external limiting membrane/ellipsoid zone, but above the RPE layer. They had a hyperreflective border with a hyporeflective core and a clear posterior tail of hyper-transmission. RESULTS: The present study analyzed 137 eyes of 137 patients. Eighty (58.4%) eyes had acute disease at presentation, 48 (35%) eyes had chronic disease, and eight (5.8%) eyes had resolved CSC. Subretinal hyporeflective globules were seen in 27 (21.8%) eyes, of which choroidal caverns were seen in seven (5.1%) eyes. Twenty-five eyes with chronic CSC and only two eyes with acute CSC had subretinal hyporeflective globules. Three eyes with resolved CSC had subretinal hyporeflective globules. CONCLUSION: We describe subretinal hyporeflective globule as a novel optical coherence tomography (OCT) finding in cases of CSC and describe its clinical correlates.

Mechanistic Studies on the Reaction of Nitrocobalamin with Glutathione: Kinetic evidence for formation of an aquacobalamin intermediate.

The essential but also toxic gaseous signaling molecule nitric oxide is scavenged by the reduced vitamin B12 complex cob(II)alamin. The resulting complex, nitroxylcobalamin (NO--Cbl(III)), is rapidly oxidized to nitrocobalamin (NO2Cbl) in the presence of oxygen; however it is unlikely that nitrocobalamin is itself stable in biological systems. Kinetic studies on the reaction between NO2Cbl and the important intracellular antioxidant, glutathione (GSH), are reported. In this study, a reaction pathway is proposed in which the ß-axial ligand of NO2Cbl is first substituted by water to give aquacobalamin (H2OCbl+), which then reacts further with GSH to form glutathionylcobalamin (GSCbl). Independent measurements of the four associated rate constants k1, k-1, k2, and k-2 support the proposed mechanism. These findings provide insight into the fundamental mechanism of ligand substitution reactions of cob(III)alamins with inorganic ligands at the ß-axial site.

Engineering Photo-Crosslinked Antimicrobial Coating to Tackle Catheter-Associated Infections In Vivo.

Microbial colonization on urinary and intravascular catheter surfaces results in steeply rising cases of catheter-associated infections as well as blood stream infections. Currently marketed efforts include impregnation and loading of antimicrobials and antiseptics that leach out into the local environment and inactivate microbes. However, they suffer from uncontrolled release, induction of resistance, and undesired toxicity. Here, in this manuscript, we have developed a photocurable, covalent coating on catheters using quaternary benzophenone-based amide (QSM-1). The coating was found to be active against drug-resistant bacteria and fungi. The coating inactivated stationary and persister cells of superbug MRSA and inhibited the formation of biofilms with retained activity against broad-spectrum bacteria when challenged in realistic urinary conditions. The coating was seen to be biocompatible in vitro and in vivo. Remarkably, the coated catheters showed reduced fouling and >99.9% reduction in bacterial burden when implanted in vivo in a mice model of subcutaneous implantation. We conceive the possibility of application of QSM-1-coated catheters in the healthcare settings to tackle the notorious catheter-associated nosocomial infections.

Small molecular adjuvants repurpose antibiotics towards Gram-negative bacterial infections and multispecies bacterial biofilms.

Gram-negative bacterial infections pose a significant challenge due to two major resistance elements, including the impermeability of the outer membrane and the overexpression of efflux pumps, which contribute to antibiotic resistance. Additionally, the coexistence of multispecies superbugs in mixed species biofilms further complicates treatment, as these infections are refractory to most antibiotics. To address this issue, combining obsolete antibiotics with non-antibiotic adjuvants that target bacterial membranes has shown promise in combating antibacterial resistance. However, the clinical translation of this cocktail therapy has been hindered by the toxicity associated with these membrane active adjuvants, mainly due to a limited understanding of their structure and mechanism of action. Towards this goal, herein, we have designed a small molecular adjuvant by tuning different structural parameters, such as the balance between hydrophilic and hydrophobic groups, spatial positioning of hydrophobicity and hydrogen bonding interactions, causing moderate membrane perturbation in bacterial cells without any toxicity to mammalian cells. Moderate membrane perturbation not only enhances the internalization of antibiotics, but also increases the intracellular concentration of drugs by hampering the efflux machinery. This revitalises the efficacy of various classes of antibiotics by 32-512 fold, without inducing toxicity. The leading combination not only exhibits potent bactericidal activity against A. baumannii biofilms but also effectively disrupts mature multispecies biofilms composed of A. baumannii and methicillin-resistant Staphylococcus aureus (MRSA), which is typically resistant to most antibiotics. Importantly, the combination therapy demonstrates good biocompatibility and excellent in vivo antibacterial efficacy (>99% reduction) in a skin infection model of A. baumannii. Interestingly, A. baumannii shows reduced susceptibility to develop resistance against the leading combination, underscoring its potential for treating multi-drug resistant infections.

Biocide loaded shear-thinning hydrogel with anti-biofilm efficacy cures topical infection.

The continuous intervention of multidrug-resistant (MDR) bacterial infections worsens and slows the dynamicity of natural wound healing processes. Fortunately, antibiotics, metal ions, or metal nanoparticle-loaded antimicrobial hydrogels have been developed to tackle infections at injury sites and speed up the healing process. Despite their success, these marketed released based hydrogels are still limited owing to their lack of broad-spectrum activity, inability to tackle biofilm-associated infections, susceptibility towards resistance development, fast release kinetics, and mild to moderate toxicity. To address these shortcomings, we report the development of a biocompatible, shear-thinning, injectable gellan-gelatin hydrogel loaded with a peptidomimetic potent biocide (ASAM-10). The hydrogel upon sustained biocide release (60% within 72 h), displays a broad-spectrum antibacterial activity with negligible in vitro (hemolysis < 20%) and in vivo toxicity (no adverse effects on dermal layer of mice). Besides tackling bacterial dormant subpopulation (1-6 Log reduction), the optimized hydrogel is able to disrupt the preformed bacterial biofilm and even kill the biofilm-trapped pathogens with enhanced pathogenicity. Above all, the lead hydrogel was proficient in tackling methicillin-resistant Staphylococcus aureus (MRSA) wound infections in a mouse model through its safe topical administration. Overall, the biocide-loaded hydrogel can be considered as a promising candidate to combat MDR chronic infections at the wound site.