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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
38
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.