Format

Send to

Choose Destination
See comment in PubMed Commons below
Antimicrob Agents Chemother. 2012 May;56(5):2223-30. doi: 10.1128/AAC.06288-11. Epub 2012 Mar 5.

Targeting persisters for tuberculosis control.

Author information

1
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. yzhang@jhsph.edu

Abstract

Mycobacterial persisters, the survivors from antibiotic exposure, necessitate the lengthy treatment of tuberculosis (TB) and pose a significant challenge for our control of the disease. We suggest that persisters in TB are heterogeneous in nature and comprise various proportions of the population depending on the circumstances; the mechanisms of their formation are complex and may be related to those required for persistence in chronic infection. Results from recent studies implicate multiple pathways for persister formation, including energy production, the stringent response, global regulators, the trans-translation pathway, proteasomal protein degradation, toxin-antitoxin modules, and transporter or efflux mechanisms. A combination of specifically persister-targeted approaches, such as catching them when active and susceptible either by stimulating them to "wake up" or by intermittent drug dosing, the development of new drugs, the use of appropriate drug combinations, and combined chemotherapy and immunotherapy, may be needed for more effective elimination of persisters and better treatment of TB. Variations in levels of persister formation and in host genetics can play a role in the outcome of clinical treatment, and thus, these may entail personalized treatment regimens.

PMID:
22391538
PMCID:
PMC3346619
DOI:
10.1128/AAC.06288-11
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center