Antresh Kumar

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Papers by Antresh Kumar

Antimicrobial effect of pimozide by targeting ROS‐mediated killing in Staphylococcus aureus

Biotechnology and Applied Biochemistry

Mucormycosis threats: A systemic review

Journal of Basic Microbiology

Synthesis and Regulation of Fungal Secondary Metabolites

Microorganisms for Sustainability, 2019

Fungi are well known for their ability to produce a multitude of secondary metabolites (SMs) whic... more Fungi are well known for their ability to produce a multitude of secondary metabolites (SMs) which act as a weapon of defense to protect themselves against parasites and predators. A variety of fungal SMs have proved to serve as an important factor for decades. The synthesis of SMs in fungi is a complex, multi-step process and is stage-specific under specialized conditions. SMs are primarily synthesized by non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) enzymes. The genes encoded for SM synthesis are often located in the cluster form at the sub-telomere region. The SM biosynthetic gene cluster comprises of genes encoding for NRPS/PKS, a transcription factor, and other accessory genes essential for assembly and maturation of SM. The regulation of SM synthesis in fungi can be achieved by pathway-specific (in-clustered transcription factor), global regulatory proteins and chromatin remodeling. The regulatory protein-encoding gene present in each gene cluster is considered to be a crucial regulatory circuit of the SM biosynthetic pathway. Moreover, the regulation of fungal SM biosynthesis is also guided by global regulatory proteins responsive to pH, carbon, nitrogen, light/dark, and other environmental cues. Histone modifications by methylation and acetylation often altered the chromatin structure; as a result, these changes repress or express the genes of SM biosynthetic pathway. Taken together, we conclude that fungal SM ability as antibiotics to toxins is useful to mankind.

Effects of Nitrogenus Sources on Antifungal Secondrymetabolite Production by Aspergillus Nidulans

Curcumin Epigenetically Represses Histone Acetylation of Echinocandin B Producing Emericella rugulosa

Physiologia

Echinocandin B is a natural product that possesses potent antifungal property against a wide arra... more Echinocandin B is a natural product that possesses potent antifungal property against a wide array of fungi. This antifungal agent is produced by Emericella rugulosa. The biosynthetic genes of echinocandin B are physically organized in two gene clusters (ecd and hty). The ecd gene cluster comprises 12 genes (ecdA–L). On the other hand, hty contains six genes (htyA–F). These gene clusters regulate Echinocandin B expression and play an essential role in chromatin modifications. The present study elucidates the epigenetic regulatory network of echinocandin B production using Histone acetyltransferase (HAT) inhibitor; curcumin using transcriptional gene expression analysis. The High-performance liquid chromatography (HPLC) analysis revealed suppression of the echinocandin B levels in the cells treated with curcumin. Curcumin was also found to repress the expression of different ecd genes by several folds. Taken together, we conclude that curcumin targets echinocandin B production by inh...

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Review of: "Saponins and their synergistic antibacterial activity with traditional antibiotics against Staphylococcus aureus and Escherichia coli: Review

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Un-regulatory actions of ecdB transcription factor present in echinocandin B biosynthetic gene cluster

Journal of biotechnology & biomaterials, Dec 14, 2017

Statement of the Problem: Candida infection is a major threat for, immunocompromised patients, in... more Statement of the Problem: Candida infection is a major threat for, immunocompromised patients, in transplantation, AIDS and malignancy patients undergone in ICU which accounts ~40% ICU mortality. Echinocandin B (ECB), a cyclic hexa-peptide antifungal is mainly used for the treatment of such Candida and Aspergillus infectious pathogens that refractory to Azoles and Polyenes. It inhibits 1,3-β-glucan synthase by blocking the cell wall synthesis. The biosynthetic gene cluster of Echinocandin B of Aspergillus nidulans NRRL 11440 was identified, it contains various structural genes such as NRPS, transporters, acyl-AMP ligase, various oxygenases adjacent to a transcription factor ecdB. The regulatory mechanism and function of this ecdB transcription factor was not so far known which has been targeted to be explored in present study. Methodology & Theoretical Orientation: The functional analysis of ecdB transcription factor was investigated by gene knockout strategy. The ECB production and transcriptional analysis was observed by HPLC and semi-quantitative PCR respectively. Findings: The Echinocandin B production in ecdB knockout strain (ΔecdB) and WT and no significant difference was found both at production and expression level as compared to WT, while expression of ecdB gene is completely lost in ΔecdB strain. Moreover, growth, sporulation, spore germination rates and morphology were also found same with no difference as compared to WT. Conclusion & Significance: Taken together, ecdB present with in the gene cluster has no direct role in regulation the ECB biosynthesis, in addition to that it also not involved in developmental and morphological process of the cell. We suggest that other regulatory network present outside the cluster may have role in ECB biosynthesis. Biography Arvind Kumar has completed his MTech in Biotechnology and recently engaged in the research as PhD Fellow in Central University of South Bihar, Patna, (India). He has expertise in elucidation of regulatory network involved in fungal secondary metabolite biosynthetic gene clusters. He also has expertise in the screening, isolation and characterization of bioactive secondary metabolites from fungi as well as plants. Recently, he has started working in the field of molecular characterization and elucidation of regulatory network involved in echinocandin B production. Previously, he has identified a new plant derived insecticide for mosquito control and patented for its commercial use.

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Design and development of conductive nanomaterials for electrochemical sensors: a modern approach

Materials Today Chemistry, 2022

Synthesis and Regulation of Fungal Secondary Metabolites

Microorganisms for Sustainability, 2019

Ajeet BJ paper copy

ab initio modelling of ICL3 and the surface-charge distribution on the Mdr1 protein

Application of Silver Nanoparticles as a New Alternative Antiviral Agent for SARS-CoV-2: A Review

Current Nanoscience, 2021

Background: Today, SARS-CoV-2 (COVID-19), a viral disease caused by the novel coronavirus (a tiny... more Background: Today, SARS-CoV-2 (COVID-19), a viral disease caused by the novel coronavirus (a tiny crowned virus), has become one of the threats for human beings all over the world and caused the death of millions of people worldwide. Many vaccines have been developed and administered to people in several countries; however, due to their propensity to create new strains, it appears that curing all corona strains will be challenging. So, it is necessary to identify the structure of the virus, mechanism of action, and its antiviral activities against drugs and other functional materials. Method: AgNPs have unique physicochemical and antimicrobial properties. This review describes the structure and nature of the virus and the mechanism of action of an antiviral drug such as silver nanoparticles (AgNPs) with the virus. In addition, different methods for synthesis of AgNPs, application of AgNPs as an antiviral agent against influenza virus, human immuno deficiency virus (HIV), herpes simp...

Progression of β-Lactam Resistance in Staphylococcus aureus

Staphylococcus aureus [Working Title], 2021

Staphylococcus aureus is a notorious human pathogen that causes superficial and invasive infectio... more Staphylococcus aureus is a notorious human pathogen that causes superficial and invasive infections both in nosocomial and community-acquired settings. The prevalence of staphylococcal infections became more challenging after emerging resistance against topical antibiotics. S. aureus evolved resistance to β-lactam antibiotics due to modification and expression of penicillin-binding proteins (PBP), inactivation of drug by β-lactamase synthesis, limiting uptake of drug by biofilm formation, and reducing uptake by expression of efflux pump. The wave of resistance was first observed in penicillin by β-lactamase production and PBPs modification. The second wave of resistance emerged to methicillin by appearing methicillin-resistant S. aureus (MRSA) strains. Cephalosporin has long been used as the last resort for preventing MRSA infections, but resistant strains appeared during treatment. In progression to control MRSA or related infections, carbapenems have been used but strains develope...

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Functional characterization of host toxic EcdB transcription factor protein of echinocandin B biosynthetic gene cluster

Biotechnology and Applied Biochemistry, 2019

Short title: Functional characterization of EcdB protein of Emericella rugulosa.

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Information theoretic measures and mutagenesis identify a novel linchpin residue involved in substrate selection within the nucleotide-binding domain of an ABCG family exporter Cdr1p

Archives of Biochemistry and Biophysics, 2019

Information theoretic measures and mutagenesis identify a novel linchpin residue involved in subs... more

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Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against Staphylococcus aureus

Drug discoveries & therapeutics, 2018

Staphylococcus aureus is an opportunistic pathogen, responsible for superficial and invasive infe... more Staphylococcus aureus is an opportunistic pathogen, responsible for superficial and invasive infections both in nosocomial and community-acquired settings. The incidences of infection have become more problematic attributable to emerging drug resistance and biofilm formation. These challenges suggest the need for new antimicrobial agents against S. aureus. In present work, we purified a fungal xenobiotic (FI3) which elicits a potent antimicrobial activity against a list of tested microbes including methicillin sensitive (MSSA) and methicillin resistance (MRSA) S. aureus. The cell growth of MSSA and MRSA were completely ceased with the 1× minimum inhibitory concentration (MIC); 32 µg/mL and 128 µg/mL, respectively. The cell viability severely decreased within 90 min, due to disturbance of membrane homeostasis. This bactericidal effect was enhanced at lower pH (pH 4) with a speculation to retain positive charge. The FI3 potently disrupts biofilm adherence at 64 µg/mL and found to be a...

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Green synthesis and characterization of silver nanoparticles using Boerhaavia diffusa plant extract and their anti bacterial activity

Industrial Crops and Products, 2014

a b s t r a c t Green synthesis of silver nanoparticles was carried out using Boerhaavia diffusa ... more a b s t r a c t Green synthesis of silver nanoparticles was carried out using Boerhaavia diffusa plant extract as a reduc- ing agent. The biosynthesized AgNPs were characterized by SEM-EDAX, XRD, TEM, UV-Vis, and FT-IR spectroscopy techniques. UV-Vis spectroscopy of prepared silver colloidal solution showed absorp- tion maxima at 418 nm. XRD and TEM analysis revealed that AgNPs are face-centered, cubic structure being spherical in shape with an average particle size of 25 nm. The AgNPs were tested for antibacte- rial activity against three fish bacterial pathogens viz., Aeromonas hydrophila, Pseudomonas fluorescens and Flavobacterium branchiophilum and they demonstrated highest sensitivity toward F. branchiophilum when compared to other two bacterial pathogens. © 2013 Elsevier B.V. All rights reserved.

A key structural domain of the Candida albicans Mdr1 protein

Biochemical Journal, 2012

A major multidrug transporter, MDR1 (multidrug resistance 1), a member of the MFS (major facilita... more A major multidrug transporter, MDR1 (multidrug resistance 1), a member of the MFS (major facilitator superfamily), invariably contributes to an increased efflux of commonly used azoles and thus corroborates their direct involvement in MDR in Candida albicans. The Mdr1 protein has two transmembrane domains, each comprising six transmembrane helices, interconnected with extracellular loops and ICLs (intracellular loops). The introduction of deletions and insertions through mutagenesis was used to address the role of the largest interdomain ICL3 of the MDR1 protein. Most of the progressive deletants, when overexpressed, eliminated the drug resistance. Notably, restoration of the length of the ICL3 by insertional mutagenesis did not restore the functionality of the protein. Interestingly, most of the insertion and deletion variants of ICL3 became amenable to trypsinization, yielding peptide fragments. The homology model of the Mdr1 protein showed that the molecular surface-charge distri...

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Ouabain potentiates the antimicrobial activity of aminoglycosides against Staphylococcus aureus

BMC Complementary and Alternative Medicine, 2019

Background: Staphylococcus aureus is a notorious pathogen which often causes nosocomial and commu... more Background: Staphylococcus aureus is a notorious pathogen which often causes nosocomial and community attained infections. These infections steadily increased after evolving the resistance due to indecorous practice of antibiotics and now become a serious health issue. Ouabain is a Na + /K +-ATPase inhibitor that leads to increase the heart contraction in patients with congestive heart failure. Methods: In the present study, in vitro antimicrobial effect of ouabain together with aminoglycosides was determined against clinical and non-clinical S. aureus strains. Using checkerboard, Gentamycin uptake and biofilm assays, we analysed he interactions of ouabain with aminoglycosides. Results: Ouabain induced the staphylocidal potency of aminoglycosides by remarkably reducing the MIC of gentamycin (GEN) by 16 (0.25 μg/mL), 8 folds (0.5 μg/mL) amikacin (AMK); and 16 folds (1.0 μg/mL) with kanamycin (KAN), compared to their individual doses. OBN severely reduced cell viability within 60 min with GEN (1 μg/mL), KAN (2 μg/mL) and 90 min with AMK (1 μg/mL). This bactericidal effect was enhanced due to GEN uptake potentiated by 66% which led to increase the cell permeability as revealed by leakage of bacterial ATP and nitrocefin assay. The biofilm adherence disrupted by 80 and 50% at 5 mg/mL and 1.5 mg/mL OBN and 50 and 90% biofilm formation was inhibited at 5 mg/mL (MBIC 50) and 10 mg/mL (MBIC 90), respectively. Moreover, OBN with GEN further induced biofilm inhibition by 67 ± 5% at pH 7.0. Conclusions: Taken together, we established that OBN synergizes the antimicrobial activity of aminoglycosides that induces cell killing due to intracellular accumulation of GEN by disturbing cell homeostasis. It may be proven an effective approach for the treatment of staphylococcal infections.

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A novel catalytic mechanism for ATP hydrolysis employed by the N-terminal nucleotide-binding domain of Cdr1p, a multidrug ABC transporter of Candida albicans

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2008

Although essentially conserved, the N-terminal nucleotide-binding domain (NBD) of Cdr1p and other... more Although essentially conserved, the N-terminal nucleotide-binding domain (NBD) of Cdr1p and other fungal transporters has some unique substitutions of amino acids which appear to have functional significance for the drug transporters. We have previously shown that the typical Cys193 in Walker A as well as Trp326 and Asp327 in the Walker B of N-terminal NBD (NBD-512) of Cdr1p has acquired unique roles in ATP binding and hydrolysis. In the present study, we show that due to spatial proximity, fluorescence resonance energy transfer (FRET) takes place between Trp326 of Walker B and MIANS [2-(4-maleimidoanilino) naphthalene-6sulfonic acid] on Cys193 of Walker A motif. By exploiting FRET, we demonstrate how these critical amino acids are positioned within the nucleotide-binding pocket of NBD-512 to bind and hydrolyze ATP. Our results show that both Mg 2+ coordination and nucleotide binding contribute to the formation of the active site. The entry of Mg 2+ into the active site causes the first large conformational change that brings Trp326 and Cys193 in close proximity to each other. We also show that besides Trp326, typical Glu238 in the Q-loop also participates in coordination of Mg 2+ by NBD-512. A second conformational change is induced when ATP, but not ADP, docks into the pocket. Asn328 does sensing of the γ-phosphate of the substrate in the extended Walker B motif, which is essential for the second conformational change that must necessarily precede ATP hydrolysis. Taken together our results imply that the uniquely placed residues in NBD-512 have acquired critical roles in ATP catalysis, which drives drug extrusion.

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