ArticleMolecular microbiology2014
Lethality of sortase depletion in Actinomyces oris caused by excessive membrane accumulation of a surface glycoprotein.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 56 citations in OpenAlex.
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- Molecular basis for dual functions in pilus assembly modulated by the lid of a pilus-specific sortase.The Journal of biological chemistry · 2024Article
- Single-Copy Gene Editing of a Cell Wall-Anchored Pilin in Actinomyces oris.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Detection of Cell Wall-Anchoring Machinery by Immunogold-Labeling Thin-Section Electron Microscopy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Development of a xylose-inducible promoter and riboswitch combination system for manipulating gene expression inApplied and environmental microbiology · 2023Article
- HicA Toxin-Based Counterselection Marker for Allelic Exchange Mutations in Fusobacterium nucleatum.Applied and environmental microbiology · 2023Article
- A review on pilus assembly mechanisms in Gram-positive and Gram-negative bacteria.Cell surface (Amsterdam, Netherlands) · 2022Article
- A cell wall-anchored glycoprotein confers resistance to cation stress in Actinomyces oris biofilms.Molecular oral microbiology · 2022Article
- A conserved signal-peptidase antagonist modulates membrane homeostasis of actinobacterial sortase critical for surface morphogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- LytR-CpsA-Psr Glycopolymer Transferases: Essential Bricks in Gram-Positive Bacterial Cell Wall Assembly.International journal of molecular sciences · 2021Review
- New Paradigms of Pilus Assembly Mechanisms in Gram-Positive Actinobacteria.Trends in microbiology · 2020Review
- A Cell-based Screen in Actinomyces oris to Identify Sortase Inhibitors.Scientific reports · 2020Article
- Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Sortase-Dependent Proteins Promote Gastrointestinal Colonization by Enterococci.Infection and immunity · 2019Article
- Article
- Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii.Journal of bacteriology · 2018Article
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6 authors at 2 institutions in 1 country.
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Abstract
Sortase, a cysteine-transpeptidase conserved in Gram-positive bacteria, anchors on the cell wall many surface proteins that facilitate bacterial pathogenesis and fitness. Genetic disruption of the housekeeping sortase in several Gram-positive pathogens reported thus far attenuates virulence, but not bacterial growth. Paradoxically, we discovered that depletion of the housekeeping sortase SrtA was lethal for Actinomyces oris; yet, all of its predicted cell wall-anchored protein substrates (AcaA-N) were individually dispensable for cell viability. Using Tn5-transposon mutagenesis to identify factors that upend lethality of srtA deletion, we uncovered a set of genetic suppressors harbouring transposon insertions within genes of a locus encoding AcaC and a LytR-CpsA-Psr (LCP)-like protein. AcaC was shown to be highly glycosylated and dependent on LCP for its glycosylation. Upon SrtA depletion, the glycosylated form of AcaC, hereby renamed GspA, was accumulated in the membrane. Overexpression of GspA in a mutant lacking gspA and srtA was lethal; conversely, cells overexpressing a GspA mutant missing a membrane-localization domain were viable. The results reveal a unique glycosylation pathway in A. oris that is coupled to cell wall anchoring catalysed by sortase SrtA. Significantly, this novel phenomenon of glyco-stress provides convenient cell-based assays for developing a new class of inhibitors against Gram-positive pathogens.
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