Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation
Abstract
Bacterial binding to host receptors underlies both commensalism and pathogenesis. Many streptococci adhere to protein-attached carbohydrates expressed on cell surfaces using Siglec-like binding regions (SLBRs). The precise glycan repertoire recognized may dictate whether the organism is a strict commensal versus a pathogen. However, it is currently not clear what drives receptor selectivity. Here, we use five representative SLBRs and identify regions of the receptor binding site that are hypervariable in sequence and structure. We show that these regions control the identity of the preferred carbohydrate ligand using chimeragenesis and single amino acid substitutions. We further evaluate how the identity of the preferred ligand affects the interaction with glycoprotein receptors in human saliva and plasma samples. As point mutations can change the preferred human receptor, these studies suggest how streptococci may adapt to changes in the environmental glycan repertoire.
- Authors:
-
[3];
[6];
[7];
[6];
[3];
[2]
- Univ. of California, San Francisco, CA (United States); Northern California Institute for Research and Education, San Francisco, CA (United States)
- Vanderbilt Univ., Nashville, TN (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
- Vanderbilt Univ., Nashville, TN (United States); Belmont University, Nashville, TN (United States)
- Erzincan Binali Yildirim University (Turkey); Univ. of California, Davis, CA (United States)
- Univ. of California, Davis, CA (United States)
- Vanderbilt Univ., Nashville, TN (United States) ; Univ. of Arkansas, Little Rock, AR (United States)
- Meharry Medical College, Nashville, TN (United States)
- Northwestern Univ., Argonne, IL (United States)
- Univ. of Alabama, Huntsville, AL (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); Department of Veterans Affairs; National Institutes of Health (NIH); American Heart Association; USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute of General Medical Sciences; Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; Beth Israel Deaconess Medical Center; Harvard Medical School
- OSTI Identifier:
- 1870240
- Grant/Contract Number:
- AC05-00OR22725; AC02-76SF00515; AC02-06CH11357; R01AI41513; U01CA221244; R01AI130684; R01AI106987; R03DE029516; GM137458; 14GRNT20390021; 17SDG33660424; GM007628; GM008320; EY007135; P41GM103393; 085P1000817; R24GM098791; P41GM103694
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 13; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; glycobiology; lectins; pathogens; x-ray crystallography
Citation Formats
Bensing, Barbara A., Stubbs, Haley E., Agarwal, Rupesh, Yamakawa, Izumi, Luong, Kelvin, Solakyildirim, Kemal, Yu, Hai, Hadadianpour, Azadeh, Castro, Manuel A., Fialkowski, Kevin P., Morrison, KeAndreya M., Wawrzak, Zdzislaw, Chen, Xi, Lebrilla, Carlito B., Baudry, Jerome Y., Smith, Jeremy C., Sullam, Paul M., and Iverson, T. M.. Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation. United States: N. p., 2022.
Web. doi:10.1038/s41467-022-30509-y.
Bensing, Barbara A., Stubbs, Haley E., Agarwal, Rupesh, Yamakawa, Izumi, Luong, Kelvin, Solakyildirim, Kemal, Yu, Hai, Hadadianpour, Azadeh, Castro, Manuel A., Fialkowski, Kevin P., Morrison, KeAndreya M., Wawrzak, Zdzislaw, Chen, Xi, Lebrilla, Carlito B., Baudry, Jerome Y., Smith, Jeremy C., Sullam, Paul M., & Iverson, T. M.. Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation. United States. https://doi.org/10.1038/s41467-022-30509-y
Bensing, Barbara A., Stubbs, Haley E., Agarwal, Rupesh, Yamakawa, Izumi, Luong, Kelvin, Solakyildirim, Kemal, Yu, Hai, Hadadianpour, Azadeh, Castro, Manuel A., Fialkowski, Kevin P., Morrison, KeAndreya M., Wawrzak, Zdzislaw, Chen, Xi, Lebrilla, Carlito B., Baudry, Jerome Y., Smith, Jeremy C., Sullam, Paul M., and Iverson, T. M.. Wed .
"Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation". United States. https://doi.org/10.1038/s41467-022-30509-y. https://www.osti.gov/servlets/purl/1870240.
@article{osti_1870240,
title = {Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation},
author = {Bensing, Barbara A. and Stubbs, Haley E. and Agarwal, Rupesh and Yamakawa, Izumi and Luong, Kelvin and Solakyildirim, Kemal and Yu, Hai and Hadadianpour, Azadeh and Castro, Manuel A. and Fialkowski, Kevin P. and Morrison, KeAndreya M. and Wawrzak, Zdzislaw and Chen, Xi and Lebrilla, Carlito B. and Baudry, Jerome Y. and Smith, Jeremy C. and Sullam, Paul M. and Iverson, T. M.},
abstractNote = {Bacterial binding to host receptors underlies both commensalism and pathogenesis. Many streptococci adhere to protein-attached carbohydrates expressed on cell surfaces using Siglec-like binding regions (SLBRs). The precise glycan repertoire recognized may dictate whether the organism is a strict commensal versus a pathogen. However, it is currently not clear what drives receptor selectivity. Here, we use five representative SLBRs and identify regions of the receptor binding site that are hypervariable in sequence and structure. We show that these regions control the identity of the preferred carbohydrate ligand using chimeragenesis and single amino acid substitutions. We further evaluate how the identity of the preferred ligand affects the interaction with glycoprotein receptors in human saliva and plasma samples. As point mutations can change the preferred human receptor, these studies suggest how streptococci may adapt to changes in the environmental glycan repertoire.},
doi = {10.1038/s41467-022-30509-y},
journal = {Nature Communications},
number = 1,
volume = 13,
place = {United States},
year = {2022},
month = {5}
}
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