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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [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.
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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.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
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)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1575069
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 36; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
coaggregation
gram-positive bacteria
pilus assembly
pilus length
sortase