Synthesis and antimicrobial evaluation of gamma borono phosphonate compounds in Escherichia coli and Mycobacterium smegmatis

ABSTRACT Poor-quality medicines undermine the treatment of infectious diseases, such as tuberculosis, which require months of treatment with rifampin and other drugs. Rifampin resistance is a critical concern for tuberculosis treatment. While subtherapeutic doses of medicine are known to select for antibiotic resistance, the effect of drug degradation products on the evolution of resistance is unknown. Here, we demonstrate that substandard drugs that contain degraded active pharmaceutical ingredients select for gene alterations that confer resistance to standard drugs. We generated drug-resistant Escherichia coli and Mycobacterium smegmatis strains by serially culturing bacteria in the presence of the rifampin degradation product rifampin quinone. We conducted Sanger sequencing to identify mutations in rifampin-resistant populations. Strains resistant to rifampin quinone developed cross-resistance to the standard drug rifampin, with some populations showing no growth inhibition at maximum concentrations of rifampin. Sequencing of the rifampin quinone-treated strains indicated that they acquired mutations in the DNA-dependent RNA polymerase B subunit. These mutations were localized in the rifampin resistance-determining region (RRDR), consistent with other reports of rifampin-resistant E. coli and mycobacteria. Rifampin quinone-treated mycobacteria also had cross-resistance to other rifamycin class drugs, including rifabutin and rifapentine. Our results strongly suggest that substandard drugs not only hinder individual patient outcomes but also restrict future treatment options by actively contributing to the development of resistance to standard medicines.

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ANTIMICROBIAL EVALUATION OF DIFFERENT EXTRACTS OF NIRGUNDI LEAF AGAINST PSEUDOMONAS AERUGINOSA, STAPHYLOCOCCUS AUREUS, ESCHERICHIA COLI AND KLEBSIELLA AEROGENES

International Journal of Research in Ayurveda and Pharmacy ◽

10.7897/2277-4343.094100 ◽

2018 ◽

Vol 9 (4) ◽

pp. 13-16

Author(s):

Satyapal Sharma ◽

Gaurav Sharma ◽

Sudipta Kumar Rath

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Klebsiella Aerogenes ◽

Antimicrobial Evaluation

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Design, Synthesis, and Antimicrobial Evaluation of New Annelated Pyrimido[2,1-c][1,2,4]triazolo[3,4-f][1,2,4]triazines

Molecules ◽

10.3390/molecules25061339 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1339 ◽

Cited By ~ 1

Author(s):

Islam H. El Azab ◽

Nadia A.A. Elkanzi

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Positive Control ◽

Design Synthesis ◽

Aspergillus Brasiliensis ◽

In Vitro Investigation ◽

Bacillus Subtilis Atcc ◽

Antimicrobial Evaluation

A series of 34 new pyrimido[2,1-c][1,2,4]triazine-3,4-diones were synthesized and fully characterized using IR, NMR, MS, and microanalytical analysis. In vitro investigation of 12 compounds of this series revealed promising antimicrobial activity of the conjugates 15a and 15f–j that were tagged with electron-withdrawing groups, with sensitivities ranging from 77% to as high as 100% of the positive control. The investigation of antimicrobial activity included Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6535, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 8739 (EC), and fungal strains Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404.

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Protective role of Mycobacterium leprae small heat-shock protein in heterologous hosts, Escherichia coli and Mycobacterium smegmatis, grown under stress

Journal of Medical Microbiology ◽

10.1099/jmm.0.057851-0 ◽

2013 ◽

Vol 62 (7) ◽

pp. 959-967 ◽

Cited By ~ 9

Author(s):

Jayapal Jeya Maheshwari ◽

Kuppamuthu Dharmalingam

Keyword(s):

Escherichia Coli ◽

Heat Shock ◽

Heat Shock Protein ◽

Mycobacterium Smegmatis ◽

Small Heat Shock Protein ◽

Mycobacterium Leprae ◽

Protective Role ◽

Low Oxygen

The aim of this study is to examine the in vivo role of a small heat-shock protein (sHsp18) from Mycobacterium leprae in the survival of heterologous recombinant hosts carrying the gene encoding this protein under different environmental conditions that are normally encountered by M. leprae during its infection of the human host. Using an Escherichia coli system where shsp18 expression is controlled by its native promoter, we show that expression of shsp18 is induced under low oxygen tension, nutrient depletion and oxidative stress, all of which reflect the natural internal environment of the granulomas where the pathogen resides for long periods. We demonstrate the in vivo chaperone activity of sHsp18 through its ability to confer survival advantage to recombinant E. coli at heat-shock temperatures. Additional evidence for the protective role of sHsp18 was obtained when Mycobacterium smegmatis harbouring a copy of shsp18 was found to multiply better in human macrophages. Furthermore, the autokinase activity of sHsp18 protein demonstrated for what is believed to be the first time in this study implies that some of the functions of sHsp18 might be controlled by the phosphorylation state of this protein. Results from this study suggest that shsp18 might be one of the factors that facilitate the survival and persistence of M. leprae under stress and autophosphorylation of sHsp18 protein could be a mechanism used by this protein to sense changes in the external environment.

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