Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

Drug Tolerance in Mycobacteria Replicating in a Microdialyser Mediated by an Efflux Mechanism Frederick Balagadde 1 , Brilliant B. Luthuli 1 , Georgiana Purdy 2 . 1 KwaZulu-Natal Research Institute for TB-HIV (K-RITH), Durban, South Africa, 2 Oregon Health and Sciences University, Portland, OR, USA. Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis is the world’s deadliest curable disease, responsible for an estimated 1.5 million deaths annually. A major challenge in controlling TB is the requirement for prolonged (6 to 9 months of) multidrug therapy to overcome drug-tolerant mycobacteria that persist in human tissues, although the same drugs can sterilize genetically identical mycobacteria growing in axenic culture within days. Recent studies have shown that the intracellular (or intramacrophage) mycobacterial sub-population, which makes up an essential component of human TB infection, is significantly more tolerant to antibiotics compared to the extracellular population. To investigate intramacrophage drug tolerance, we present a microdialyser—a microfabricated physical cell culture system that mimics confinement of replicating mycobacteria, such as in a macrophage during infection. Furthermopre, unlike bactericidal antibiotics, bacteriostatic drugs ultimately depend upon the immune system for sterilization, and are therefore poor treatment options where the immune system is compromised, as in the case of co-infection with HIV. Distinguishing between bacteriostatic and bactericidal action of antimicrobial drugs can be cumbersome using conventional drug susceptibility testing methods but the microdialyser can rapidly resolve this distinction for antimicrobial agents.

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