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1.
Infect Dis Now ; 54(2): 104865, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38350558

ABSTRACT

OBJECTIVES: To identify the potential target genes for detection of Orientia tsutsugamushi (OT) in pediatric acute encephalitis syndrome (pAES). METHODS: DNA was extracted from whole blood of 100 pAES cases having tested positive (n = 41) and negative (n = 59) for scrub typhus (ST) by IgM ELISA. These samples were subjected to standard PCR for 56 kDa, 47 kDa, 16 s rRNA, groEL, traD genes and the newly identified 27 kDa gene. RESULTS: Among the selected gene targets, 56 kDa demonstrated its superiority for OT detection over the other tested genes. The presence of OT was confirmed via PCR targeting 56 kDa gene in 17 out of the 41 (41.4 %) IgM-positive ST AES cases and 38 out of the 59 (64.4 %) ST IgM negative cases. None of the other gene targets were amplified. CONCLUSION: Integration of serological diagnosis with molecular diagnostics targeting the 56 kDa gene for routine testing of AES patients would facilitate detection of OT in AES endemic regions.


Subject(s)
Acute Febrile Encephalopathy , Scrub Typhus , Child , Humans , Scrub Typhus/diagnosis , Acute Febrile Encephalopathy/diagnosis , Enzyme-Linked Immunosorbent Assay , Immunoglobulin M , Polymerase Chain Reaction
2.
Bioorg Chem ; 106: 104454, 2021 01.
Article in English | MEDLINE | ID: mdl-33213895

ABSTRACT

Being crucial part of plant-based novel discovery of drug from natural resources, a study was done to explore the antibacterial potential of curcumin mimics in combination with antibiotics against multidrug resistant isolates of Pseudomonas aeruginosa. The best candidate Van D, a curcumin mimics reduced the MIC of tetracycline (TET) up to 16 folds against multidrug resistant clinical isolates. VanD further inhibited the efflux pumps as evident by ethidium bromide efflux and by in-silico docking studies. In another experiment, it was also found that Van D inhibits biofilm synthesis. This derivative kills the KG-P2, an isolate of P. aeruginosa in a time dependent manner, the post-antibiotic effect (PAE) of tetracycline was extended as well as mutant prevention concentration (MPC) of TET was also decreased. In Swiss albino mice, Van D reduced the proinflammatory cytokines concentration. In acute oral toxicity study, this derivative was well tolerated and found to be safe up to 1000 mg/kg dose. To the best of our knowledge, this is the first report on curcumin mimics as synergistic agent via inhibition of efflux pump.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Chalcones/therapeutic use , Drug Resistance, Bacterial/drug effects , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/toxicity , Bacterial Outer Membrane Proteins/metabolism , Biofilms/drug effects , Chalcones/chemical synthesis , Chalcones/metabolism , Chalcones/toxicity , Curcumin/chemistry , Curcumin/pharmacology , Drug Design , Drug Synergism , Female , Male , Membrane Transport Proteins/metabolism , Mice, Inbred BALB C , Microbial Sensitivity Tests , Molecular Docking Simulation , Protein Binding , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Tetracycline/pharmacology
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