skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes

Abstract

Assembly of pili on the gram-positive bacterial cell wall involves 2 conserved transpeptidase enzymes named sortases: One for polymerization of pilin subunits and another for anchoring pili to peptidoglycan. How this machine controls pilus length and whether pilus length is critical for cell-to-cell interactions remain unknown. We report here in Actinomyces oris, a key colonizer in the development of oral biofilms, that genetic disruption of its housekeeping sortase SrtA generates exceedingly long pili, catalyzed by its pilus-specific sortase SrtC2 that possesses both pilus polymerization and cell wall anchoring functions. Remarkably, the srtA-deficient mutant fails to mediate interspecies interactions, or coaggregation, even though the coaggregation factor CafA is present at the pilus tip. Furthermore, increasing ectopic expression of srtA in the mutant progressively shortens pilus length and restores coaggregation accordingly, while elevated levels of shaft pilins and SrtC2 produce long pili and block coaggregation by SrtA+ bacteria. With structural studies, we uncovered 2 key structural elements in SrtA that partake in recognition of pilin substrates and regulate pilus length by inducing the capture and transfer of pilus polymers to the cell wall. Evidently, coaggregation requires proper positioning of the tip adhesin CafA via modulation of pilus length by the housekeeping sortasemore » SrtA.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [2];  [3];  [5];  [6];  [7]
  1. Univ. of California, Los Angeles, CA (United States). Div. of Oral Biology and Medicine
  2. Univ. of Texas Health Science Center, Houston, TX (United States). Dept. of Microbiology & Molecular Genetics
  3. Univ. of Chicago, Chicago, IL (United States). Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering; Argonne National Lab. (ANL), Lemont, IL (United States). Structural Biology Center
  4. Yale School of Medicine, New Haven, CT (United States). Dept. of Microbial Pathogenesis
  5. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry
  6. Univ. of Connecticut, Storrs, CT (United States). Dept. of Medicine, Neag Comprehensive Cancer Center
  7. Univ. of California, Los Angeles, CA (United States). Div. of Oral Biology and Medicine and Molecular Biology Inst.
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research; University of Texas Health Science Center at Houston; National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
OSTI Identifier:
1575069
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 36; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; coaggregation; gram-positive bacteria; pilus assembly; pilus length; sortase

Citation Formats

Chang, Chungyu, Wu, Chenggang, Osipiuk, Jerzy, Siegel, Sara D., Zhu, Shiwei, Liu, Xiangan, Joachimiak, Andrzej, Clubb, Robert T., Das, Asis, and Ton-That, Hung. Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes. United States: N. p., 2019. Web. doi:10.1073/pnas.1907733116.
Chang, Chungyu, Wu, Chenggang, Osipiuk, Jerzy, Siegel, Sara D., Zhu, Shiwei, Liu, Xiangan, Joachimiak, Andrzej, Clubb, Robert T., Das, Asis, & Ton-That, Hung. Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes. United States. https://doi.org/10.1073/pnas.1907733116
Chang, Chungyu, Wu, Chenggang, Osipiuk, Jerzy, Siegel, Sara D., Zhu, Shiwei, Liu, Xiangan, Joachimiak, Andrzej, Clubb, Robert T., Das, Asis, and Ton-That, Hung. 2019. "Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes". United States. https://doi.org/10.1073/pnas.1907733116. https://www.osti.gov/servlets/purl/1575069.
@article{osti_1575069,
title = {Cell-to-cell interaction requires optimal positioning of a pilus tip adhesin modulated by gram-positive transpeptidase enzymes},
author = {Chang, Chungyu and Wu, Chenggang and Osipiuk, Jerzy and Siegel, Sara D. and Zhu, Shiwei and Liu, Xiangan and Joachimiak, Andrzej and Clubb, Robert T. and Das, Asis and Ton-That, Hung},
abstractNote = {Assembly of pili on the gram-positive bacterial cell wall involves 2 conserved transpeptidase enzymes named sortases: One for polymerization of pilin subunits and another for anchoring pili to peptidoglycan. How this machine controls pilus length and whether pilus length is critical for cell-to-cell interactions remain unknown. We report here in Actinomyces oris, a key colonizer in the development of oral biofilms, that genetic disruption of its housekeeping sortase SrtA generates exceedingly long pili, catalyzed by its pilus-specific sortase SrtC2 that possesses both pilus polymerization and cell wall anchoring functions. Remarkably, the srtA-deficient mutant fails to mediate interspecies interactions, or coaggregation, even though the coaggregation factor CafA is present at the pilus tip. Furthermore, increasing ectopic expression of srtA in the mutant progressively shortens pilus length and restores coaggregation accordingly, while elevated levels of shaft pilins and SrtC2 produce long pili and block coaggregation by SrtA+ bacteria. With structural studies, we uncovered 2 key structural elements in SrtA that partake in recognition of pilin substrates and regulate pilus length by inducing the capture and transfer of pilus polymers to the cell wall. Evidently, coaggregation requires proper positioning of the tip adhesin CafA via modulation of pilus length by the housekeeping sortase SrtA.},
doi = {10.1073/pnas.1907733116},
url = {https://www.osti.gov/biblio/1575069}, journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 36,
volume = 116,
place = {United States},
year = {Mon Aug 19 00:00:00 EDT 2019},
month = {Mon Aug 19 00:00:00 EDT 2019}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks
journal, February 2016


Stabilizing Isopeptide Bonds Revealed in Gram-Positive Bacterial Pilus Structure
journal, December 2007


Sortases and pilin elements involved in pilus assembly of Corynebacterium diphtheriae: Pilus assembly in corynebacteria
journal, May 2004


Dali server: conservation mapping in 3D
journal, May 2010


Assembly of pili on the surface of Bacillus cereus vegetative cells
journal, October 2007


Sortase enzymes in Gram-positive bacteria: Sortase enzymes in Gram-positive bacteria
journal, November 2011


Sorting sortases: a nomenclature proposal for the various sortases of Gram-positive bacteria
journal, April 2005


The molecular switch that activates the cell wall anchoring step of pilus assembly in gram-positive bacteria
journal, September 2008


Lethality of sortase depletion in A ctinomyces oris caused by excessive membrane accumulation of a surface glycoprotein
journal, September 2014


The Bacteriophage T7 Virion Undergoes Extensive Structural Remodeling During Infection
journal, January 2013


Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM
journal, May 2013


Structure of sortase, the transpeptidase that anchors proteins to the cell wall of Staphylococcus aureus
journal, May 2001


Assembly and role of pili in group B streptococci
journal, June 2006


Pilin and Sortase Residues Critical for Endocarditis- and Biofilm-Associated Pilus Biogenesis in Enterococcus faecalis
journal, August 2013


Sortase-Catalyzed Assembly of Distinct Heteromeric Fimbriae in Actinomyces naeslundii
journal, February 2007


Crystal Structure of Streptococcus pyogenes Sortase A : IMPLICATIONS FOR SORTASE MECHANISM
journal, January 2009


A comprehensive guide to pilus biogenesis in Gram-negative bacteria
journal, May 2017


Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae
journal, November 2007


Sortase A Utilizes an Ancillary Protein Anchor for Efficient Cell Wall Anchoring of Pili in Streptococcus agalactiae
journal, June 2008


Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode
journal, June 2013


A Type I Signal Peptidase Is Required for Pilus Assembly in the Gram-Positive, Biofilm-Forming Bacterium Actinomyces oris
journal, May 2016


Protein secretion and surface display in Gram-positive bacteria
journal, April 2012


Pili of Gram-positive bacteria: roles in host colonization
journal, November 2012


Biogenesis of the Gram-positive bacterial cell envelope
journal, December 2016


Cell Wall Anchor Structure of BcpA Pili in Bacillus anthracis
journal, October 2008


Endocarditis and biofilm-associated pili of Enterococcus faecalis
journal, October 2006


Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development
journal, January 2008


Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm development
journal, February 2014


Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii
journal, February 2018


Sortase Activity Is Controlled by a Flexible Lid in the Pilus Biogenesis Mechanism of Gram-Positive Pathogens ,
journal, November 2009


Automated electron microscope tomography using robust prediction of specimen movements
journal, October 2005


Structure of the sortase AcSrtC-1 from Actinomyces oris
journal, February 2011


RrgA is a pilus-associated adhesin in Streptococcus pneumoniae
journal, October 2007


Computer Visualization of Three-Dimensional Image Data Using IMOD
journal, January 1996


Surface components of Porphyromonas gingivalis
journal, February 2009


Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens
journal, October 2005


Dual Function of a Tip Fimbrillin of Actinomyces in Fimbrial Assembly and Receptor Binding
journal, April 2011


Arbuscular cell invasion coincides with extracellular vesicles and membrane tubules.
text, January 2019


Visualization of the type III secretion sorting platform of Shigella flexneri
journal, January 2015


Assembly of pili on the surface of Corynebacterium diphtheriae: Corynebacterium diphtheriae pili
journal, November 2003


Relationship of pili to colonial morphology among pathogenic and nonpathogenic species of Neisseria
journal, February 1977