Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 20, Pages 6437-6442Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1504967112
Keywords
peptidoglycan; flippase; MurJ; sigM; lipid II
Categories
Funding
- NIH [GM086466, RC2 GM092616, AI083365-01, AI099144, GM102790]
- Center of Excellence for Translational Research [U19 AI109764]
- American Heart Association [14POST18480014]
Ask authors/readers for more resources
Bacterial surface polysaccharides are synthesized from lipid-linked precursors at the inner surface of the cytoplasmic membrane before being translocated across the bilayer for envelope assembly. Transport of the cell wall precursor lipid II in Escherichia coli requires the broadly conserved and essential multidrug/oligosaccharidyl- lipid/polysaccharide (MOP) exporter superfamily member MurJ. Here, we show that Bacillus subtilis cells lacking all 10 MOP superfamily members are viable with only minor morphological defects, arguing for the existence of an alternate lipid II flippase. To identify this factor, we screened for synthetic lethal partners of MOP family members using transposon sequencing. We discovered that an uncharacterized gene amj (alternate to MurJ; ydaH) and B. subtilis MurJ (murJ(Bs); formerly ytgP) are a synthetic lethal pair. Cells defective for both Amj and MurJ(Bs) exhibit cell shape defects and lyse. Furthermore, expression of Amj or MurJ(Bs) in E. coli supports lipid II flipping and viability in the absence of E. coli MurJ. Amj is present in a subset of gram-negative and gram-positive bacteria and is the founding member of a novel family of flippases. Finally, we show that Amj is expressed under the control of the cell envelope stress-response transcription factor sigma(M) and cells lacking MurJ(Bs) increase amj transcription. These findings raise the possibility that antagonists of the canonical MurJ flippase trigger expression of an alternate translocase that can resist inhibition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available