Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity

DSpace/Manakin Repository

Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity

Citable link to this page

 

 
Title: Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity
Author: Rego, E. Hesper; Audette, Rebecca E.; Rubin, Eric J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Rego, E. Hesper, Rebecca E. Audette, and Eric J. Rubin. 2017. “Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity.” Nature 546 (7656): 153-157. doi:10.1038/nature22361. http://dx.doi.org/10.1038/nature22361.
Full Text & Related Files:
Abstract: Summary Paragraph While microorganisms are often studied as populations, the behavior of single, individual cells can have profound consequences. For example, tuberculosis, caused by the bacterial pathogen Mycobacterium tuberculosis, requires months of antibiotic therapy even though the bulk of the bacterial population rapidly dies. Shorter courses lead to high rates of relapse because subpopulations of bacilli can survive despite being genetically identical to those that are easily killed 1. In fact, mycobacteria create variability every time a cell divides, producing daughter cells with different sizes and growth rates 2, 3. The mechanism(s) that underlie this high-frequency variation and how variability relates to survival of the population are unknown. Here we show that mycobacteria actively create heterogeneity. Using a fluorescent reporter and a FACS-based transposon screen, we find that deletion of lamA, a gene of previously unknown function, decreases the amount of heterogeneity in the population by decreasing asymmetric polar growth. LamA has no known homologs in other organisms, but is highly conserved across mycobacterial species. We find that LamA is a member of the mycobacterial division complex (“the divisome”). It inhibits growth at nascent new poles, creating asymmetry in polar growth. The kinetics of killing individual cells that lack lamA are more uniform and more rapid with rifampicin and certain drugs that target the cell wall. Our results show that mycobacteria encode a non-conserved protein that controls the pattern of cell growth, resulting in a population that is both heterogeneous and better able to survive antibiotic pressure.
Published Version: doi:10.1038/nature22361
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567998/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493282
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters