NYMC Faculty Publications

Recombinational Exchange of M-Fibril and T-Pilus Genes Generates Extensive Cell Surface Diversity in the Global Group a Population

Debra E. Bessen, Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, New York, USA.Follow
Bernard W. Beall, Respiratory Disease Branch, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
Andrew Hayes, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Weihua Huang, Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, New York, USA.
Jeanne M. DiChiara, Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, New York, USA.
Srinivasan Velusamy, Respiratory Disease Branch, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
Hervé Tettelin, Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Keith A. Jolley, Department of Biology, University of Oxford, Oxford, United Kingdom.
John T. Fallon, Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, New York, USA.Follow
Sopio Chochua, Respiratory Disease Branch, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.
Mosaed S. Alobaidallah, Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, New York, USA.
Charlie Higgs, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Timothy C. Barnett, The Marshall Centre for Infectious Diseases Research and Training, School of Biomedical Sciences, University of Western Australia, Nedlands, Australia.
John T. Steemson, School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Thomas Proft, School of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Mark R. Davies, Eagle Global Scientific, LLC, Atlanta, Georgia, USA.

Author Type(s)

Faculty, Resident/Fellow

DOI

10.1128/mbio.00693-24

Journal Title

mBio

First Page

e0069324

Document Type

Article

Publication Date

5-8-2024

Department

Pathology, Microbiology and Immunology

Abstract

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.

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