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Title: Porin-Mediated transport of fluoroquinolones in Mycobacterium Tuberculosis
Keywords: Fluoroquinolones, mycobacteria, tuberculosis, transport, porin, latency
Issue Date: 10-Jan-2013
Citation: JANSY PASSIFLORA SARATHY (2013-01-10). Porin-Mediated transport of fluoroquinolones in Mycobacterium Tuberculosis. ScholarBank@NUS Repository.
Abstract: Subpopulations of Mycobacterium tuberculosis are able to survive antibiotic treatment for a prolonged time in a dormant state. We used an established model of nutrient deprivation to shift down M. tuberculosis from growth to non-replicating survival. LC/MS techniques were used to quantify drug penetration in replicating and nutrient-starved bacilli. We found that intracellular concentrations of fluoroquinolones, rifamycins and linezolid were lower during non-replication. Our characterization of fluoroquinolone uptake in M. tuberculosis led us to conclude that they are most likely taken up via a facilitated passive uptake process. We have shown that polyamines, which are porin channel inhibitors, effectively reduce the permeability of the mycobacterial outer membrane to fluoroquinolones. Gene expression studies showed that several outer membrane proteins are significantly down-regulated during non-replication. We concluded that a reduction in intracellular accumulation due to the modification of porin-mediated uptake processes contributes to the drug resistance demonstrated by M. tuberculosis during latency.
Appears in Collections:Ph.D Theses (Open)

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