Browsing by Author "Minakshi Sahu"

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A Randomized, Placebo-controlled, Double-blind Clinical Trial of Bacteriophage Cocktails in Chronic Wound Infections
(SAGE Publications Inc., 2024) Subhash Lal Karn; Satyanam Kumar Bhartiya; Arvind Pratap; Sanjay Kumar Saroj; Rajesh Kumar; Minakshi Sahu; Mayank Gangwar; Gopal Nath
Background: Chronic wounds are prevalent globally at endemic proportions. The common features associated with chronic wounds are prolonged inflammatory phase, infection with multidrug-resistant (MDR) bacteria, and subsequent biofilm formation. The present randomized-controlled trial (RCT) study was undertaken on chronic wounds of ≥6 weeks longer duration using customized phages to evaluate the efficacy and safety of bacteriophage therapy. Methods: The study was conducted from December 2021 to August 2023. Thirty patients in each of the arms (placebo and bacteriophage) were recruited with chronic wounds. The patients, both arms, received the conventional treatment of wound debridement, local antiseptics, and local and systemic antibiotics at the discretion of the treating surgeon. However, before applying the customized bacteriophage cocktail or placebo, the wound surface was thoroughly washed to remove the residual antiseptics. The phage cocktails or placebo were applied on alternate days. The wounds were evaluated using the Bates-Jensen Wound Assessment Tool for the progress of wound healing. Results: A total of 93.3% of the wound became sterile in 39 days (median sterility time), followed by complete healing by the end of 90 days in the phage group. Contrary to this, 83.3% of those on placebo therapy remained colonized by original bacteria or additional new bacteria without healing for up to 90 days. Conclusion: With the well-designed RCT, we could conclude that customized bacteriophage therapy using bacteriophage cocktails will definitely cure the chronic wound, irrespective of age, sex, diabetes status, and infection by MDR bacteria. © The Author(s) 2024.
Bacteriophage therapy a promising alternative treatment approach for infections caused by multidrug-resistant (MDR) Enterococcus species
(Elsevier B.V., 2025) Minakshi Sahu; Sudhir Kumar Singh; Meenakshi Singh; Alka Shukla; Gopal Nath
The 21st-century real threat is the upsurge of microbial resistance and the ineffectiveness of drugs to even a minor injury and common infection, which further leads to an increase in mortality rate. Enterococci bacterial species, such as Enterococcus faecalis and Enterococcus faecium, are common human pathogens that cause many diseases, such as bacteremia, urinary tract infections (UTI), meningitis, and endocarditis. The higher occurrence of MDR bacteria and the ineffectiveness of available antibiotics in treating infectious diseases have prompted a search for viable alternatives, such as bacteriophage therapy and combinational therapy of bacteriophage with standard antibiotics. The current review focuses on the role of Enterococcus spp. as the causative agent of life-threatening infections and how the bacteriophages are effective against them in reference to different clinical settings and their ability to thwart biofilm formation. Furthermore, combining antibiotics and bacteriophage improves killing efficacy and prevents phage resistance development. Compared to conventional antibiotics alone, the synergy between the antibiotics and phages disrupts the biofilm efficiently in MDR biofilm infections. Finally, the application of bacteriophage endolysin has been discussed, gathering significant attention worldwide due to their cell wall lysing propensity and potential therapeutic usage for treating enterococci-associated infectious diseases. © 2025
Efficacy of bacteriophage cocktails administered through mucosal and non-mucosal routes for urinary tract infections caused by Enterobacter cloacae: A preclinical study
(Academic Press, 2025) Srishti Singh; Alok Kumar Singh; Alakh Narayan Singh; Sudhir Kumar Singh; Virendra Bahadur Yadav; Mayank Gangwar; Minakshi Sahu; Deepak Kumar; Gopal Nath
This preclinical study assessed the effectiveness of a phage cocktail in completely curing Enterobacter cloacae-associated urinary tract infections (UTIs) in a mouse model, employing various routes and dosages (both in quantity and frequency). Three lytic phages, designated ΦENT1, ΦENT2, and ΦENT3, were identified and characterised phenotypically using transmission electron microscopy (TEM) and genotypically through ERIC and restriction enzyme analysis. To induce a UTI, ten groups of female Swiss albino mice were inoculated with 100 μL containing 1 × 109 CFU/mL via the urethral route with E. cloacae GNENT11213. The mice were subsequently treated with the phage cocktail via subcutaneous, oral, transurethral, and rectal routes. The efficacy of these routes was optimised at two doses of phages, namely 1 × 109 PFU/mL (5 mice) and 1 × 105 PFU/mL (5 mice). Furthermore, the levels of Endotoxins and Interleukin-6 (IL-6) were measured to assess the negative impact of phage therapy. Our findings indicated that E. cloacae GNENT11213 could be effectively eliminated with one dosage of 1 × 109Plaque-Forming Units per mouse (PFU/mouse) and two doses of the phage cocktail containing 1 × 105 PFU/mouse administered through the urethra (local mucosa). Interestingly, higher concentrations of phage particles and multiple doses were necessary for other mucosal routes, such as oral and rectal administration, to effectively eradicate E. cloacae GNENT11213 at any stage of acute illness UTI. Furthermore, phage treatment did not significantly alter the levels of IL-6 and Endotoxins. Non-mucosal routes, such as subcutaneous, were ineffective in curing the infection. © 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Gut Microbiome in Obesity: A Narrative Review of Mechanisms, Interventions, and Future Directions
(Springer, 2025) Ranjeet Kumar Vishwakarma; Priyanka Gautam; Minakshi Sahu; Gopal Nath; Bhupendra Singh Yadav
Obesity has reached pandemic levels worldwide and is increasingly recognized as a multifactorial condition beyond excess caloric intake and sedentary lifestyle. Accumulating evidence emphasizes that the gut microbiota (GM), primarily composed of Firmicutes and Bacteroidetes, plays a crucial role in regulating energy balance, immune response, and host metabolism. Gut dysbiosis, characterized by reduced microbial diversity and altered phylum-level composition and shifts toward commonly observed higher Firmicutes-to-Bacteroidetes ratios (although this finding is inconsistent across studies), contributes to enhanced energy harvest, systemic inflammation, and metabolic dysfunction. Key mechanisms involve GM production of short-chain fatty acids (SCFAs) and modulation of hormonal signals, including leptin, ghrelin, insulin, GLP-1, and PYY, alongside interactions via the gut-brain axis. These pathways link microbial composition to appetite regulation, fat storage, and energy balance. Emerging microbiome-targeted therapies, such as probiotics, prebiotics, dietary modulation (e.g., fiber-rich diets), fecal microbiota transplantation, and bacteriophage therapy, show promise in restoring GM balance, promoting weight loss, and improving metabolic health, though results vary and require further validation. Despite advances in metagenomics and metabolomics, gaps persist in establishing causality and long-term efficacy. The integration of GM data with host genetics, diet, and environmental factors through systems biology has the potential to facilitate personalized management of obesity. This review synthesizes the GM’s role in obesity pathogenesis and hormonal regulation, highlighting therapeutic potential and research directions for microbiota-based prevention and treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
In vitro efficacy of bacteriophage and colistin combinations in eradicating biofilm formed by colistin-resistant Enterobacter cloacae complex
(Elsevier B.V., 2025) Srishti Singh; Alok Kumar Singh; Virendra Bahadur Yadav; Sudhir Kumar Singh; Minakshi Sahu; Alakh Narayan Singh; Gopal Nath
In the case of dry antibiotic pipelines and the emergence of resistance against last-resort antibiotics, such as colistin, alternative medicinal techniques have been necessitated. In this context, the potential of phages as a viable alternative to antibiotics is a beacon of hope. Phage and antibiotic combination therapy is a compelling solution to the problem of phage or bacterial mutant generation. In most studies, phage and antibiotic combinations were used simultaneously. Only a few phages have been recently utilised before antibiotics, significantly reducing the bacterial load in vitro and in vivo. Therefore, we investigated the additive action of phage antibiotic combinations in preventing biofilm formation against three different colistin-resistant clinical isolates of the Enterobacter cloacae complex, specifically Enterobacter cloacae and Enterobacter hormaechei, at various time points with varying phage concentrations. We used different phage concentrations and sub-MICs of colistin combinations to determine the optimal phage concentration that shows synergy against three different clinical isolates of the Enterobacter cloacae complex. We also investigated the optimal time for applying antibiotics after phage treatment to eradicate Enterobacter cloacae complex in both planktonic and biofilm states. The cross-colistin susceptibility of colistin-resistant strain after co-treatment with SIM (Phage antibiotic simultaneous) and AF (Antibiotic added 8 h before phage) was also evaluated using the broth dilution method. In brief, applying phage before 8 h or 6 h of colistin, i.e. PF (Phage first followed by antibiotics) treatment at a dosage of 106 PFU/mL, was an effective sequential therapy for eliminating the biofilm and the planktonic form of Enterobacter cloacae complex. The Institutional Ethics Committee of Banaras Hindu University (Institute of Medical Sciences), Varanasi, with reference number Dean/2024/IAEC/6876, has approved this in vitro study. © 2025 The Authors
In-vitro analysis of biofilm formation and synergistic antibiotic-phage therapy for amoxicillin-resistant Escherichia coli
(Springer Science and Business Media Deutschland GmbH, 2025) Ranjeet Kumar Vishwakarma; Bhupendra Singh Yadav; Priyanka Gautam; Minakshi Sahu; Ayu Singh; Ashish Kumar; Gopal Nath
Biofilm formation by Escherichia coli (E. coli) significantly enhances bacterial resistance to antibiotics, complicating treatment, particularly in amoxicillin-resistant strains. Bacteriophage therapy demonstrates potential in treating biofilm-related infections, and the combination of phages and antibiotics (phage-antibiotic synergy, PAS) further enhances efficacy. This is the first study to evaluate PAS using penicillin-class antibiotics against multidrug-resistant (MDR) Gram-negative bacteria, E. coli. E. coli-specific lytic bacteriophages were isolated and characterized. PAS was evaluated in both planktonic and biofilm forms using sub-inhibitory concentrations of AMC. The viability of biofilm and planktonic forms was assessed not only by colony counts but also by flow cytometry. Moreover, morphological alterations were evaluated by scanning electron microscopy (SEM), and genomic alterations by PAS were analyzed through whole genome fingerprinting using ERIC PCR. In biofilm and planktonic form, phage first achieved effective bacterial killing after 24 h, when 106 PFU/mL was supplemented with amoxicillin clavulanic acid (AMC) combination after 7 h for optimal PAS killing. PAS treatment significantly reduced biofilm viability compared to phage therapy only, while AMC was not effective at all. SEM revealed disrupted cell walls, detachment of flagella, and rupture of bacterial cells, as well as changes in morphology and biofilm matrix in combination therapy. Phage-first treatment with ɸA3 followed by AMC after 7 h effectively eradicates multidrug-resistant E. coli, causing genomic changes that restore antibiotic sensitivity at subinhibitory doses, potentially addressing antimicrobial resistance. In PAS, a cocktail of phages may be advised to avoid the emergence of phage mutant strains. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.