Browsing by Author "Sudhir Kumar Singh"

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A novel nanotherapeutic approach: Dual action of green-synthesized silver nanoparticles from Clerodendrum serratum against MDR-ESKAPE pathogens with wound healing potential
(Editions de Sante, 2025) Ritu Raj Patel; Pandey Priya Arun; Vidyasagar; Aradhana Mishra; Sudhir Kumar Singh; Samer Singh; Brahmeshwar Mishra; Meenakshi Singh
The rapid emergence of multidrug-resistant (MDR) ESKAPE pathogens in healthcare settings, particularly chronic wound infections presents a critical challenge. Moreover, with antibiotic resistance reaching alarming levels and conventional treatments failing against biofilm-associated infections, there is an urgent need to develop novel and effective therapeutic strategies. In this study, silver nanoparticles (AgNPs) synthesized via a green method using Clerodendrum serratum leaf extract, along with their polyethylene glycol-coated derivative (PEG-AgNPs), were evaluated for their antibacterial and wound-healing potential. PEG-AgNPs demonstrated superior antibacterial efficacy, with significantly lower minimum inhibitory concentration (MIC) values (0.3906–12.5 μg/mL) compared to AgNPs (3.125–25 μg/mL). Time-kill studies further confirmed that PEG-AgNPs exhibited enhanced bactericidal properties. Mechanistic investigations revealed that their antibacterial activity resulted from bacterial cell membrane rupture, leading to cytoplasmic content leakage, as confirmed by FACS analysis. Furthermore, biofilm formation by these pathogens was evaluated, and the nanoparticles demonstrated remarkable anti-biofilm potency, particularly against Acinetobacter baumannii and Pseudomonas aeruginosa. The LC-MS analysis of C. serratum leaf extract revealed bioactive phytoconstituents, which were subjected to molecular docking studies against biofilm-forming factors in P. aeruginosa and A. baumannii confirming strong binding interactions. Additionally, the prepared nanoparticle-based gel formulations significantly enhanced in vivo wound healing in both uninfected and infected (A. baumannii and P. aeruginosa) wounds, highlighting their potential as dual-action therapeutic agents for inhibiting MDR pathogens and simultaneously promoting tissue regeneration. Therefore, these findings suggest that green synthesized nanoparticles, particularly PEG-AgNPs hold promise as novel interventions for combating MDR-ESKAPE infected wounds. © 2025 Elsevier B.V.
Advanced CMD predictor screening approach coupled with cellular automata-artificial neural network algorithm for efficient land use-land cover change prediction
(Elsevier Ltd, 2024) Kanhu Charan Panda; Ram Mandir Singh; Sudhir Kumar Singh
The prediction of future land use and land cover (LULC) change is essential for natural resource management and the development of environmental monitoring strategies, especially for a non-resilient system. Thus, a novel LULC prediction model was proposed by coupling a hybrid predictor screening approach with the Cellular Automata coupled Artificial Neural Network (CA-ANN) approach. The hybrid predictor screener was formed by integrating the outcomes of Correlation Coefficient (CC), Mutual Information (MI), and Decision Tree (DT) methods and termed as the CMD technique. The CA-ANN model was trained by LULC maps of 1995 and 2005 and tested by the map of 2020 for these four sets of variables (i.e., CC, MI, DT, and CMD). The results revealed that the CMD predictors were the most influential variables for LULC prediction, followed by the DT-based variables. In contrast, the CC-based predictors were found to be the least effective, followed by the MI variables. Thus, the CMD-CA-ANN model was established as the benchmark model in this study. The study showed that elevation and distance from roads were more critical variables for LULC prediction compared to slope and aspect parameters. The proposed model demonstrated that by 2080, there would be an increase in the area of built-up land (5.79%), cropland (4.35%), shrubland (1.62%), and water bodies (0.3%) and a decrease in the area of forested land (1.34%) and barren land (10%) in the study area. The research has the potential to significantly contribute to the identification and management of significant environmental changes. © 2024 Elsevier Ltd
Advances in heterologous protein expression strategies in yeast and insect systems
(Elsevier, 2022) Meenakshi Singh; Smita Gupta; Arun Kumar Rawat; Sudhir Kumar Singh
The production of recombinant proteins has very high commercial and therapeutic values, especially with the increasing need for immune therapeutics and vaccines. However, none of the expression hosts can guarantee high yields of recombinant products. The eukaryotic expression system, yeast and insect cell lines, with easily accessible genetic tools, rapid growth, high cell density, and simple and inexpensive culture media, offer a better alternative to bacterial and mammalian cell expression systems. Moreover, they are harnessed to achieve a greater yield of heterologous protein with proper post-translational modifications with better protein quality due to their conserved cellular and metabolic processes to humans and other mammals. In this chapter, we discuss the established and emerging synthetic biology tools for engineered strain development of yeast and advances made towards the insect cell lines and baculovirus expression vectors that have been successfully used to express difficult-to-express proteins over the last couple of decades. © 2022 Elsevier Inc. All rights reserved.
Aerosol-PM2.5 Dynamics: In-situ and satellite observations under the influence of regional crop residue burning in post-monsoon over Delhi-NCR, India
(Academic Press Inc., 2024) Ram Pravesh Kumar; Ranjit Singh; Pradeep Kumar; Ritesh Kumar; Shadman Nahid; Sudhir Kumar Singh; Charanjeet Singh Nijjar
The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 μg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 μg/m³ (24 h) by 27–34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention. © 2024 Elsevier Inc.
Appraisal of groundwater with special reference to nitrate using statistical index approach
(Elsevier B.V., 2019) Kishan Singh Rawat; Lordwin Jeyakumar; Sudhir Kumar Singh; Vinod Kumar Tripathi
Nitrate pollution is a serious groundwater problem, a statistical index called Normalized Difference Dispersal Index (NDDI) and nonparametric spatial statistical model have been used for appraisal of groundwater samples. The groundwater monitoring data of period (2005–2013) of Kanchipuram district of state Tamil Nadu, country India has been used in this study. Maximum NDDI value enrichment is exhibited by NO3 - (+ 1.0) at many locations in studied period and it shows absolute accretion (increment of NO3 -) and at few locations NO3 - (− 1.0) shows its absolute dilution (decrement of NO3 -). Mean index values of NO3 - are + 0.01, − 0.20, − 0.19, − 0.09, − 0.11, 0.00, − 0.04 and − 0.17, respectively in year 2006, 2007, 2008, 2009, 2010, 2011, 2012 and 2013. In order to quantify the site-specific variations through index, map of NO3 - a environmentally sensitive species was generated by ArcGIS ver. 10. Statistical index based mapping is an appraisal method for evaluation and comparative assessment of NO3 - ion at different sites. The elevated index values shows that the sampling locations are not safe for consumptive use. This statistical index has potential to identify the ion specific risk zones. © 2018
Appraisal of long term groundwater quality of peninsular India using water quality index and fractal dimension
(Indian Academy of Sciences, 2017) Kishan Singh Rawat; Sudhir Kumar Singh; T. German Amali Jacintha; Jasna Nemčić-Jurec; Vinod Kumar Tripathi
A review has been made to understand the hydrogeochemical behaviour of groundwater through statistical analysis of long term water quality data (year 2005–2013). Water Quality Index (WQI), descriptive statistics, Hurst exponent, fractal dimension and predictability index were estimated for each water parameter. WQI results showed that majority of samples fall in moderate category during 2005– 2013, but monitoring site four falls under severe category (water unfit for domestic use). Brownian time series behaviour (a true random walk nature) exists between calcium (Ca2+) and electric conductivity (EC); magnesium (Mg2+) with EC; sodium (Na+) with EC; sulphate (SO2−4) with EC; total dissolved solids (TDS) with chloride (Cl−) during pre- (2005–2013) and post- (2006–2013) monsoon season. These parameters have a closer value of Hurst exponent (H) with Brownian time series behaviour condition (H =0.5). The result of times series analysis of water quality data shows a persistent behaviour (a positive autocorrelation) that has played a role between Cl− and Mg2+,Cl− and Ca2+,TDSandNa+, TDS and SO2−4,TDSandCa2+ in pre- and post-monsoon time series because of the higher value of H (>1). Whereas an anti-persistent behaviour (or negative autocorrelation) was found between Cl− and EC, TDS and EC during pre- and post-monsoon due to low value of H. The work outline shows that the groundwater of few areas needs treatment before direct consumption, and it also needs to be protected from contamination. © Indian Academy of Sciences.
Appraisal of surface and groundwater of the subarnarekha river basin, Jharkhand, India: Using remote sensing, irrigation indices and statistical technique
(CRC Press, 2016) Sandeep Kumar Gautam; Abhay K. Singh; Jayant K. Tripathi; Sudhir Kumar Singh; Prashant K. Srivastava; Boini Narsimlu; Prafull Singh
Remote sensing and Geographic Information System (GIS) are very useful tools which could be used for synoptic representation of water quality of any area (Gupta and Srivastava 2010). Land use/land cover (LULC) changes quantification through satellite remote sensing is one of the major applications; it is important for assessing global environmental change processes, supports in making policies and optimizes the use of natural resources (Srivastava et al. 2012a). The LULC types, such as agricultural land and urban area associated with human activities, often affect both the surface andgroundwater quality. Hence monitoring spatial-temporal changes is essential to understand the driving factors that influence the water quality of an area (Merchant 1994; Wu and Segerson 1995; Srivastava et al. 2013). On the other hand, GIS is an important tool for spatial analysis and integration of spatial and non-spatial data to derive useful outputs (Singh et al. 2013a) and helps in decision making. It can be used for formulating a simple and robust water quality pollutionassessment tool for rapid information generation and broadcasting to water resources managers and the public (Vasanthavigar et al. 2010; Singh et al. 2012). © 2017 by Taylor & Francis Group.
Assessment of multi-source satellite products using hydrological modelling approach
(Elsevier Ltd, 2024) Aiswarya Rani Mahanta; Kishan Singh Rawat; Nirmal Kumar; Szilard Szabo; Prashant K. Srivastava; Sudhir Kumar Singh
Multi-source satellite products performance evaluation for varied geographical locations aids in quantification of hydrological variables and is useful in the strategy making and conservation of the hydrological resources available in a basin. The work was focused on assessing utility of multi-source satellite datasets to obtain the estimation of hydrologic variables and provide solution for areas that are poorly gauged. Assessment of the multi-source-satellite products was performed for the poorly gauged river basin with the help of SWAT concerning the Palar River basin, India. We analysed time series at the monthly, seasonal, and annual scales to quantify surface runoff, water yield, ET, & PET at the calibration station and for the entire basin for the period 2003 to 2021. SWAT model estimated highest monthly water yield during November–December, with annual water yield being maximum (220 mm in 2010) and average (99.4 mm), which can be used to understand water resources for irrigation, drinking aspects, and net storage. Average monthly surface runoff patterns were similar for SWAT, TerraClimate, and FLDAS. The FLDAS and SWAT simulated surface runoff show a resemblance in pattern and magnitude for the monthly and annual time series of the average basin scenario. The monthly PET obtained from SWAT and ERA-5 show a similar pattern for the entire basin and at the calibration site. The ET derived from satellite observation has over-predicted the model output at both the calibration site and entire basin. © 2023 Elsevier Ltd
Assessment of silica content in groundwater of Peninsular Indian region using statistical techniques
(Gadjah Mada University, 2021) Kishan Singh Rawat; Sudhir Kumar Singh; Vinod Kumar Tripathi
The groundwater resources from open dug wells are the ultimate and inevitable drinking water source in Chennai municipality. These are of shallow depth of 8 to 10m with a static water depth range of 30 to 75 m. This study's objective was to assess silica (in the form of Silicon Dioxide, Si02) in groundwater and to establish their baseline concentration. Twelve wells were monitored in the study area, in some parameters, namely: Chloride (Cl-), Total Dissolved Solids (TDS), pH, Electrical Conductivity (EC), and SiO2. We examined the existing relationship between silica and other measured water quality parameters (Cl-, pH, TDS, and EC) using Spearman correlation matrix analysis in SPSS software and Normalized Difference Dispersal Index (NDDI) in Simplex Numerix software that was applied to identify the hotspots of SiO2. The water pH ranges from 8.09 to 8.37 (slightly alkaline) with an appreciable amount of TDS (730.50 to 1294.50 ppm). The groundwater also contains abundant silica (15.50 to 24.0 ppm), Cl- (106 to 438 ppm), and EC (759.50 to 1837.50 μS/cm). Further, a geostatistical tool was used to derive NDDI map of groundwater quality parameters and quantified site-specific variations in parameters, namely SiO2, Cl-, pH, TDS, and EC values. Average NDDI value enrichment was exhibited by Si02 (0.09, ≈ 0.1) it reflects accretion, while average NDDI values of Cl- (-0.09, ≈-0.1), EC (-0.04), TDS (-0.03), and pH (-0.02), it outlined that by dilution in particular groundwater parameter. © 2020 by the authors. Licensec Indonesian Journal of Geography, Indonesia. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY NC) licensehttps://crcativecommons.org/liccnscs/by-nc/4.0/.
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
Biophysical and in-silico studies on the structure-function relationship of Brugia malayi protein disulfide isomerase
(Taylor and Francis Ltd., 2024) Pawan Kumar Doharey; Pravesh Verma; Amit Dubey; Sudhir Kumar Singh; Manish Kumar; Timir Tripathi; Mona Alonazi; Nikhat Jamal Siddiqi; Bechan Sharma
Human Lymphatic filariasis is caused by parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Protein disulfide isomerase (PDI), a redox-active enzyme, helps to form and isomerize the disulfide bonds, thereby acting as a chaperone. Such activity is essential for activating many essential enzymes and functional proteins. Brugia malayi protein disulfide isomerase (BmPDI) is crucial for parasite survival and an important drug target. Here, we used a combination of spectroscopic and computational analysis to study the structural and functional changes in the BmPDI during unfolding. Tryptophan fluorescence data revealed two well-separated transitions during the unfolding process, suggesting that the unfolding of the BmPDI is non-cooperative. The binding of the fluorescence probe 8-anilino-1-naphthalene sulfonic acid dye (ANS) validated the results obtained by the pH unfolding. The dynamics of molecular simulation performed at different pH conditions revealed the structural basis of BmPDI unfolding. Detailed analysis suggested that under different pH, both the global structure and the conformational dynamics of the active site residues were differentially altered. Our multiparametric study reveals the differential dynamics and collective motions of BmPDI unfolding, providing insights into its structure-function relationship. Communicated by Ramaswamy H. Sarma. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Chronic carriers and multidrug resistance in typhoid fever: pathogenesis, challenges, and integrated control strategies
(Springer Science and Business Media Deutschland GmbH, 2025) Deepak Kumar; Sudhir Kumar Singh; Gopal Nath
Typhoid fever, a systemic disease caused by Salmonella enterica serovar Typhi (S. Typhi), remains a major global health problem, particularly in regions with poor sanitation. Despite advancements in diagnostics and treatment, S. Typhi continues to impose a heavy disease burden, worsened by the emergence of multidrug-resistant (MDR) strains. Chronic carriers, accounting for 2–5% of infections, play a crucial role in disease transmission. These carriers are often asymptomatic but intermittently shed bacteria, sustaining S. Typhi within the human population. Gallstones are strongly associated with the chronic carrier state, providing a niche for bacterial biofilm formation that enhances persistence and antibiotic resistance. Furthermore, long-term colonisation of the gallbladder is linked to an increased risk of gallbladder cancer, a condition common in typhoid-endemic areas. The pathogenesis of typhoid fever involves bacterial invasion of the gastrointestinal mucosa, evasion of innate immunity, and systemic spread. Biofilm formation on gallstones promotes long-term persistence within the gallbladder, while immune responses and intestinal microbiota dynamics influence disease progression and bacterial shedding. Current diagnostic methods, including culture and serology, often fall short in identifying carriers, necessitating the development of innovative approaches for effective surveillance and control. Treating chronic carriers remains difficult due to the biofilm-associated resistance of S. Typhi. Although cholecystectomy combined with targeted antimicrobial therapy shows promise, it does not guarantee the elimination of the carrier state. This review emphasises the importance of integrating strategies that combine improved diagnostic tools, targeted therapies, and public health interventions to reduce the burden of typhoid fever and its chronic carriers. © Springer-Verlag GmbH Germany, part of Springer Nature 2025.
Current update on the antibiotic resistance profile and the emergence of colistin resistance in Enterobacter isolates from hospital-acquired infections
(Elsevier B.V., 2025) Srishti Singh; Alok Kumar Singh; Sudhir Kumar Singh; Virendra Bahadur Yadav; Akshay Kumar; Gopal Nath
Introduction: Bacterial pathogens are becoming a growing concern as antibiotic resistance among Gram-negative bacteria rises globally. The gram-negative, facultative anaerobic, rod-shaped bacteria belonging to the Enterobacteriaceae family, Enterobacter is a nosocomial pathogen, having ubiquitous distribution in natural environments, including sewage and dairy products. These bacteria increasingly exhibit a multidrug resistance phenotype, thus becoming resilient to available treatment therapies. The fact mentioned above has resulted in them being included in the “ESKAPE” group of opportunistic pathogens, which represents a group for which no effective therapeutic options would be available in a given scenario. So, this study aimed to identify antibiotic resistance patterns in Enterobacter species collected from the bacteriological section of the Institute of Medical Sciences, Banaras Hindu University, Varanasi. Materials and Methods: Fifty-one isolates were collected from clinical samples, including urine, pus, blood, cerebrospinal fluid, sputum, and stool. All isolates were phenotypically identified using VITEK-2 automated systems (ID GNB cards). Additionally, the isolates were genotypically characterised with species-specific primers via PCR, and whole genome sequencing was performed for two isolates, followed by antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method. Concurrently, broth dilution methods were used to determine the minimum inhibitory concentration (MIC) according to CLSI 2020 guidelines. The Multiple Antibiotic Resistance Index (MARI) was calculated by dividing the number of drugs to which the bacterial isolate is resistant by the total number of antibiotics used in the experiment. Results: The highest resistance rates were observed against levofloxacin (94 %), ciprofloxacin, and ampicillin, with 92 % (47/51) of isolates demonstrating resistance. Cefazolin also exhibited a high resistance rate, with 82 % (42/51) of resistant isolates. Notably, 96.07 % of isolates showed a multiple antibiotic resistance (MAR) index greater than 0.2, indicating a significant burden of multidrug-resistant Gram-negative bacteria. In contrast, 21.56 % had an index greater than 1.0, indicating resistance to all antibiotics tested. Conclusion: This paper highlights the latest information regarding drug resistance patterns in Enterobacter isolates. The last resort for treating gram-negative bacteria is increasingly losing its effectiveness due to the emergence of colistin-resistant strains. Therefore, alternative therapies, such as phage treatment or other antimicrobial agents, must be developed to combat these superbugs. © 2025 The Authors
Delineation and classification of rural–urban fringe using geospatial technique and onboard DMSP–Operational Linescan System
(Taylor and Francis Ltd., 2018) Sk. Mustak; Naresh Kumar Baghmar; Prashant K. Srivastava; Sudhir Kumar Singh; Ramesh Binolakar
This study aims to analyse the processes and patterns of peri-urbanization using diurnal earth observation data-sets from onboard DMSP–Operational Linescan System. In this study, multiple correlation, simple and conditional linear regression are used to find out the degree of relationship and spatial behavioural pattern of the factors responsible for the urbanization. All the factors are standardized using the Analytical Hierarchy Process (AHP) coupled fuzzy membership functions. AHP is used to derive the weighting of the factors to produce the urbanity index. In total three functional zones–urban, rural and urban shadow are generated based on factor standardization and spatial contiguity index. Urban fringe is sharing ≥ 60% of Urbanity Index followed by rural fringe (39.50–60% of urbanity index) and urban shadow <39.50% of urbanity index. Shape index indicates that the city is going through unplanned development following cross to star shape growth. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
Design, synthesis and mode of action of novel 2-(4-aminophenyl)benzothiazole derivatives bearing semicarbazone and thiosemicarbazone moiety as potent antimicrobial agents
(Birkhauser Boston, 2016) Meenakshi Singh; Sudhir Kumar Singh; Mayank Gangwar; Gopal Nath; Sushil K. Singh
A novel series of substituted benzothiazoles, bearing semicarbazone and thiosemicarbazone moieties, was designed, synthesized and evaluated for their antimicrobial activity and possible mode of action. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, IR and Mass spectral data. The results revealed that compounds SC06, SC09, TS05 and TS07 have potent antibacterial activity against both Gram-positive and Gram-negative strains. Compound TS05 displayed most potent activity with MIC values of 3.91, 7.81 and 1.56 μg/ml against S. aureus, E. coli and P. aeruginosa, respectively. The results from cytoplasmic membrane permeabilization assay, FACS study as well as DNA-binding assays, evaluated against clinically relevant pathogens S. aureus and E. coli, suggest membrane perturbing as well as intracellular mode of action of this class of compounds. In addition, hemolytic activity of the compounds was measured which indicated their low cytotoxicity. © 2015 Springer Science+Business Media New York.
Design, synthesis and mode of action of some new 2-(4'-aminophenyl) benzothiazole derivatives as potent antimicrobial agents
(Bentham Science Publishers B.V., 2016) Meenakshi Singh; Sudhir Kumar Singh; Mayank Gangwar; Satheeshkumar Sellamuthu; Gopal Nath; Sushil K. Singh
Background: The rapid evolution of antibiotic resistance poses a serious threat to public health. The development of heterocyclic benzothiazole derivatives, as efficient and potential agents, has been the focus of antibacterial drug discovery. Objective: Present study attempts to evaluate the antibacterial activity and mechanism of action of novel 2-(4'- aminophenyl) benzothiazole derivatives. Methods: Antibacterial activity of novel benzothiazole derivatives was evaluated by agar disc diffusion method against a panel of susceptible Gram-positive and Gram-negative strains. The mechanism of action was explored by bactericidal kinetics, membrane depolarization, fluorescent assisted cell cytometry and DNA cleavage studies. Results: Our findings revealed that compounds A07a and A07b turned out to be the most potent analogues having minimum inhibitory concentration values in the range of 3.91-31.2 g/ml against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli. The new benzothiazole derivatives displayed different modes of action as elucidated by the studies on intact bacterial cells and plasmid DNA. The structure activity relationship studies showed prominent activity of compound A07a containing oxime moiety on carbonyl carbon along with less bulky electron releasing and lipophillic group (methoxy and chloro) in phenyl ring at C2 position of 2-(4'-aminophenyl) benzothiazole ring system. Conclusion: The potent antibacterial activity of compounds (A07a and A07b) was mediated by membrane perturbing and intracellular mode of actions. These results further validate the use of these derivatives in the treatment of microbial diseases and provide scope for further research. © 2016 Bentham Science Publishers.
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.
Evaluation of Bacteriophage Cocktail on Septicemia Caused by Colistin-Resistant Klebsiella pneumoniae in Mice Model
(Frontiers Media S.A., 2022) Aprajita Singh; Alakh Narayan Singh; Nisha Rathor; Rama Chaudhry; Sudhir Kumar Singh; Gopal Nath
Objective: The emergence of resistance against last-resort antibiotics, carbapenem and colistin, in Klebsiella pneumoniae has been reported across the globe. Bacteriophage therapy seems to be one of the most promising alternatives. This study aimed to optimize the quantity and frequency of bacteriophage cocktail dosage/s required to eradicate the Klebsiella pneumoniae bacteria in immunocompetent septicemic mice. Methods: The three most active phages ɸKpBHU4, ɸKpBHU7, and ɸKpBHU14 characterized by molecular and TEM analyses were in the form of cocktail and was given intraperitoneally to mice after inducing the septicemia mice model with a constant dose of 8 × 107 colony-forming unit/mouse (CFU/mouse) Klebsiella pneumoniae. After that, the efficacy of the phage cocktail was analyzed at different dosages, that is, in increasing, variable, constant, and repeated dosages. Furthermore, interleukin-6 and endotoxin levels were estimated with variable doses of phage cocktail. Results: We have elucidated that phage therapy is effective against the Klebsiella pneumoniae septicemia mice model and is a promising alternative to antibiotic treatments. Our work delineates that a single dose of phage cocktail with 1 × 105 plaque-forming unit/mouse (PFU/mouse) protects the mice from fatal outcomes at any stage of septicemia. However, a higher phage dosage of 1 × 1012 PFU/mice is fatal when given at the early hours of septicemia, while this high dose is not fatal at the later stages of septicemia. Moreover, multiple repeated dosages are required to eradicate the bacteria from peripheral blood. In addition, the IL-6 levels in the 1 × 105 PFU/mouse group remain lower, but in the 1 × 1012 PFU/mouse group remains high at all points, which were associated with fatal outcomes. Conclusion: Our study showed that the optimized relatively lower and multiple dosages of phage cocktails with the strict monitoring of vitals in clinical settings might cure septicemia caused by MDR bacteria with different severity of infection. Copyright © 2022 Singh, Singh, Rathor, Chaudhry, Singh and Nath.
Exploring Metal Complexes for Cancer Treatment: Mechanistic Insights and Therapeutic Potential
(Elsevier B.V., 2025) Pandey Priya Arun; Ritu Raj Patel; Sudhir Kumar Singh; Kailash Parmar; Meenakshi Singh
Recent research in the field of cancer therapeutics has explored various potential drug treatments supported by metal- based scaffolds, following the investigation and clinical application of cisplatin, which has emerged as an active anti- cancer drug. Organometallic compounds have gained significant attention in cancer therapy due to their unique ability to interact with biomolecules, providing targeted and efficient anticancer activity. This has led to the development of metallodrugs, which encompass metal-based compounds with a wider range of functionalities and mechanisms of action compared to organic molecules. However, platinum-based metal complexes have limitations in their spectrum of anti-cancer activities, often resulting in side effects and resistance. To address these challenges, extensive research has been conducted to study and develop effective alternatives to platinum-based anticancer medications, encompassing metals such as ruthenium, vanadium, copper, iron, manganese, zinc, and cobalt. Metallodrugs represent a promising new category of potential cancer treatments, renewing interest in pursuing effective anti-cancer therapies. Nanomedicine strategies offer an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and enhance therapeutic efficacy. Multifunctional nanomaterials have demonstrated the ability to improve drug delivery by increasing bioavailability and optimizing pharmacokinetics, thereby enhancing the effectiveness of chemotherapeutic agents in overcoming multidrug resistance (MDR). By gaining a deeper understanding of their distinct characteristics and mechanisms of action, there is potential to explore avenues for developing targeted and effective anti-cancer treatments. This review explores the intricate details of various metal complexes, highlighting their unique properties and modes of action in combating cancer while providing valuable insights into their potential as promising agents for developing effective and targeted anticancer therapies, paving the way for future advancements in the field. © 2025 Elsevier B.V.
Facile green synthesis of silver nanoparticles derived from the medicinal plant Clerodendrum serratum and its biological activity against Mycobacterium species
(Elsevier Ltd, 2024) Vidyasagar; Ritu Raj Patel; Sudhir Kumar Singh; Deepa Dehari; Gopal Nath; Meenakshi Singh
The emergence of multidrug-resistant mycobacterial strains is a significant crisis that has led to higher treatment failure rates and more toxic and expensive medications for tuberculosis (TB). The urgent need to develop novel therapeutics has galvanized research interest towards developing alternative antimicrobials such as silver nanoparticles (AgNPs). The current study focused on the anti-mycobacterial activity of green-synthesized AgNPs and its polyethylene glycol encapsulated derivative (PEG-AgNPs) with improved stability using the leaves extract of Clerodendrum serratum. Different characterization methods were used to analyze them. DLS analysis revealed a lower polydispersity index of PEG-AgNPs, suggesting a more uniform size distribution than that of AgNPs. The HR-TEM results revealed that the AgNPs and PEG-AgNPs have predominantly spherical shapes in the size range of 9–35 nm and 15–60 nm, respectively, while positive values of Zeta potential indicate their stability. FTIR-ATR analysis confirmed the presence of functional groups responsible for reducing and capping the bio-reduced AgNPs, whereas the XRD data established its crystalline nature. Impressively, the PEG-AgNPs exhibited maximum inhibitory activity against different Tubercular and Non-Tuberculous Mycobacterium species i.e., Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium marinum, relative to those of AgNPs and Linezolid. The flow cytometry assay showed that the anti-mycobacterial action was mediated by an increase in cell wall permeability. Notably, the results of AFM confirm their ability to inhibit mycobacterial biofilm significantly. We demonstrated the nontoxic nature of these AgNPs, explicated by the absence of hemolytic activity against human RBCs. Overall, the results suggest that PEG-AgNPs could offer a novel therapeutic approach with potential anti-mycobacterial activity and can overcome the limitations of existing TB therapies. © 2024 The Authors