Effect of various drugs on differentially detectable persisters of Mycobacterium tuberculosis generated by long-term lipid diet
| Autor: | Umamageswaran Venugopal, Gyan Chandra, Suman Bharti, Shaheb Raj Khan, Rahul K. Maurya, Manju Y. Krishnan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Microbiology (medical) food.ingredient Tuberculosis 030106 microbiology Immunology Population Antitubercular Agents Microbial Sensitivity Tests Models Biological Microbiology Clofazimine Mycobacterium tuberculosis 03 medical and health sciences chemistry.chemical_compound food Tuberculosis Multidrug-Resistant medicine Agar education education.field_of_study biology Fatty Acids medicine.disease biology.organism_classification Lipids In vitro Culture Media Phenotype 030104 developmental biology Infectious Diseases chemistry Bedaquiline Rifampicin medicine.drug |
| Zdroj: | Tuberculosis. 115:89-95 |
| ISSN: | 1472-9792 |
| Popis: | Persisters of Mycobacterium tuberculosis (Mtb) that fail to form colonies on agar media when de-stressed are termed as differentially detectable (DD) persisters. Since in the host, Mtb primarily survives by utilizing lipids, we used a long-term lipid diet model to induce DD persisters of M. tuberculosis. Persisters were induced by replacing the dextrose-containing medium with one containing fatty acids instead of dextrose (FAM). After 2, 4 or 6 weeks, CFU and most probable number assays were performed; the difference between the two gave an estimate of DD persisters. Since rifampicin has been shown to induce formation of DD persisters in vitro, one set of FAM cultures were also given short-term rifampicin stress after 2, 4 or 6 weeks. Fraction of DD persisters increased with time and rifampicin treatment enhanced the effect of fatty acids, at 2 and 4 weeks. At six weeks, even in the absence of rifampicin, ∼95% population were DD persisters. The DD persisters were vulnerable to drugs interfering with bacterial respiration such as thioridazine, bedaquiline and clofazimine. The study indicates potential formation of DD persisters of Mtb in a lipid-rich microenvironment in the host even before antibiotic therapy. |
| Databáze: | OpenAIRE |
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