Project description:Biosynthesis of metallic nanoparticles has acquired particular attention due to its economic feasibility, low toxicity, and simplicity of the process. In this study, extracellular synthesis of silver and zinc nanoparticle was carried out by Pseudomonas hibiscicola isolated from the effluent of an electroplating industry in Mumbai. Characterization studies revealed synthesis of 40 and 60 nm nanoparticles of silver (AgNP) and zinc (ZnNP), respectively, with distinct morphology as observed in TEM and its crystalline nature confirmed by XRD. DLS, zeta potential, NTA, and FTIR studies further characterized nanoparticles giving data about its size, stability, and functional groups. Considering the toxicity of nanoparticles the evaluation of antimicrobial activity was studied in the range of non-toxic concentration for normal cell lines. Silver nanoparticles were found to be the most effective antimicrobial against all tested strains and drug-resistant clinical isolates of MRSA, VRE, ESBL, MDR, Pseudomonas aeruginosa with MIC in the range of 1.25-5 mg/ml. Zinc nanoparticles were found to be specifically active against Gram-positive bacteria like Staphylococcus aureus including its drug-resistant variant MRSA. Both AgNP and ZnNP were found to be effective against Mycobacterium tuberculosis and its MDR strain with MIC of 1.25 mg/ml. The synergistic action of nanoparticles assessed in combination with a common antibiotic gentamicin (590 μg/mg) used for the treatment of various bacterial infections by Checker board assay. Silver nanoparticles profoundly exhibited synergistic antimicrobial activity against drug-resistant strains of MRSA, ESBL, VRE, and MDR P. aeruginosa while ZnNP were found to give synergism with gentamicin only against MRSA. The MRSA, ESBL, and P. aeruginosa strains exhibited MIC of 2.5 mg/ml except VRE which was 10 mg/ml for both AgNPs and ZnNPs. These results prove the great antimicrobial potential of AgNP and ZnNP against drug-resistant strains of community and hospital-acquired infections and opens a new arena of antimicrobials for treatment, supplementary prophylaxis, and prevention therapy.
Project description:The nickel (Ni)-specific chelator dimethylglyoxime (DMG) has been used for many years to detect, quantitate or decrease Ni levels in various environments. Addition of DMG at millimolar levels has a bacteriostatic effect on some enteric pathogens, including multidrug resistant (MDR) strains of Salmonella Typhimurium and Klebsiella pneumoniae. DMG inhibited activity of two Ni-containing enzymes, Salmonella hydrogenase and Klebsiella urease. Oral delivery of nontoxic levels of DMG to mice previously inoculated with S. Typhimurium led to a 50% survival rate, while 100% of infected mice in the no-DMG control group succumbed to salmonellosis. Pathogen colonization numbers from livers and spleens of mice were 10- fold reduced by DMG treatment of the Salmonella-infected mice. Using Nuclear Magnetic Resonance, we were able to detect DMG in the livers of DMG-(orally) treated mice. Inoculation of Galleria mellonella (wax moth) larvae with DMG prior to injection of either MDR K. pneumoniae or MDR S. Typhimurium led to 40% and 60% survival, respectively, compared to 100% mortality of larvae infected with either pathogen, but without prior DMG administration. Our results suggest that DMG-mediated Ni-chelation could provide a novel approach to combat enteric pathogens, including recalcitrant multi-drug resistant strains.
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain PS003.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain PS006.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain SP444.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain 04153260899A.