title: Resuscitation-promoting factors are required for β-lactam tolerance and the permeability barrier in Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Carl N
authors.initials: CN
authors.lastname: Wivagg
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Hung
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002463:Cell Membrane Permeability; D017353:Gene Deletion; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D047090:beta-Lactams