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Mechanisms of Resistance

Resuscitation-Promoting Factors Are Required for β-Lactam Tolerance and the Permeability Barrier in Mycobacterium tuberculosis

Carl N. Wivagg, Deborah T. Hung
Carl N. Wivagg
aDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
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Deborah T. Hung
aDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA
bInfectious Disease Initiative, Broad Institute, Cambridge, Massachusetts, USA
cDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
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DOI: 10.1128/AAC.06027-11
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ABSTRACT

Mycobacterial resuscitation-promoting factors (RPFs) have been of great interest since the discovery that they promote the growth of nonculturable Mycobacterium tuberculosis cells. Yet, their precise role in mycobacterial survival and infection has remained elusive. We performed a chemical screen to identify molecules that show preferential killing of a Mycobacterium tuberculosis mutant lacking RPFs over wild-type bacilli and found that the mutant has enhanced sensitivity to the β-lactam class of antibiotics. By monitoring β-lactam diffusion across the mycobacterial outer membrane, we found that the RPFs are required to maintain the outer membrane integrity, as their deletion results in an increase in outer membrane permeability.

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Resuscitation-Promoting Factors Are Required for β-Lactam Tolerance and the Permeability Barrier in Mycobacterium tuberculosis
Carl N. Wivagg, Deborah T. Hung
Antimicrobial Agents and Chemotherapy Feb 2012, 56 (3) 1591-1594; DOI: 10.1128/AAC.06027-11

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Resuscitation-Promoting Factors Are Required for β-Lactam Tolerance and the Permeability Barrier in Mycobacterium tuberculosis
Carl N. Wivagg, Deborah T. Hung
Antimicrobial Agents and Chemotherapy Feb 2012, 56 (3) 1591-1594; DOI: 10.1128/AAC.06027-11
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