1. Microbiology and Infectious Disease
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Global phenotypic profiling identifies a conserved actinobacterial cofactor for a bifunctional PBP-type cell wall synthase

  1. Joel W Sher
  2. Hoong Chuin Lim  Is a corresponding author
  3. Thomas G Bernhardt  Is a corresponding author
  1. Harvard Medical School, United States
  2. Howard Hughes Medical Institute, Harvard Medical School, United States
Research Article
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Cite this article as: eLife 2020;9:e54761 doi: 10.7554/eLife.54761

Abstract

Members of the Corynebacterineae suborder of Actinobacteria have a unique cell surface architecture and, unlike most well-studied bacteria, grow by tip-extension. To investigate the distinct morphogenic mechanisms shared by these organisms, we performed a genome-wide phenotypic profiling analysis using Corynebacterium glutamicum as a model. A high-density transposon mutagenized library was challenged with a panel of antibiotics and other stresses. The fitness of mutants in each gene under each condition was then assessed by transposon-sequencing. Clustering of the resulting phenotypic fingerprints revealed a role for several genes of previously unknown function in surface biogenesis. Further analysis identified CofA (Cgp_0016) as an interaction partner of the peptidoglycan synthase PBP1a that promotes its stable accumulation at sites of polar growth. The related Mycobacterium tuberculosis proteins were also found to interact, highlighting the utility of our dataset for uncovering conserved principles of morphogenesis for this clinically relevant bacterial suborder.

Article and author information

Author details

  1. Joel W Sher

    Department of Microbiology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0616-7632
  2. Hoong Chuin Lim

    Department of Microbiology, Harvard Medical School, Boston, United States
    For correspondence
    hoongchuin.lim@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8463-8375
  3. Thomas G Bernhardt

    Department of Microbiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
    For correspondence
    thomas_bernhardt@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3566-7756

Funding

National Institute of Allergy and Infectious Diseases (AI083365)

  • Thomas G Bernhardt

National Institute of Allergy and Infectious Diseases (AI132120)

  • Joel W Sher

Life Science Research Foundation

  • Hoong Chuin Lim

Howard Hughes Medical Institute

  • Thomas G Bernhardt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Received: December 27, 2019
  2. Accepted: March 12, 2020
  3. Accepted Manuscript published: March 13, 2020 (version 1)

Copyright

© 2020, Sher et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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