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Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci

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  • Authors: Debra E. Bessen1, Pierre R. Smeesters2, Bernard W. Beall3
  • Editors: Vincent A. Fischetti4, Richard P. Novick5, Joseph J. Ferretti6, Daniel A. Portnoy7, Julian I. Rood8
    Affiliations: 1: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY 10595; 2: Department of Pediatrics, Queen Fabiola Children’s University Hospital, and Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, 1020, Belgium; 3: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; 4: The Rockefeller University, New York, NY; 5: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 6: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 7: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 8: Australian Bacterial Pathogen Program, Department of Microbiology, Monash University, Melbourne, Australia
  • Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
  • Received 01 April 2018 Accepted 13 April 2018 Published 06 September 2018
  • Debra E. Bessen, [email protected]
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  • Abstract:

    The clinico-epidemiological features of diseases caused by group A streptococci (GAS) is presented through the lens of the ecology, population genetics, and evolution of the organism. The serological targets of three typing schemes (M, T, SOF) are themselves GAS cell surface proteins that have a myriad of virulence functions and a diverse array of structural forms. Horizontal gene transfer expands the GAS antigenic cell surface repertoire by generating numerous combinations of M, T, and SOF antigens. However, horizontal gene transfer of the serotype determinant genes is not unconstrained, and therein lies a genetic organization that may signify adaptations to a narrow ecological niche, such as the primary tissue reservoirs of the human host. Adaptations may be further shaped by selection pressures such as herd immunity. Understanding the molecular evolution of GAS on multiple levels—short, intermediate, and long term—sheds insight on mechanisms of host-pathogen interactions, the emergence and spread of new clones, rational vaccine design, and public health interventions.

  • Citation: Bessen D, Smeesters P, Beall B. 2018. Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci. Microbiol Spectrum 6(5):CPP3-0009-2018. doi:10.1128/microbiolspec.CPP3-0009-2018.


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The clinico-epidemiological features of diseases caused by group A streptococci (GAS) is presented through the lens of the ecology, population genetics, and evolution of the organism. The serological targets of three typing schemes (M, T, SOF) are themselves GAS cell surface proteins that have a myriad of virulence functions and a diverse array of structural forms. Horizontal gene transfer expands the GAS antigenic cell surface repertoire by generating numerous combinations of M, T, and SOF antigens. However, horizontal gene transfer of the serotype determinant genes is not unconstrained, and therein lies a genetic organization that may signify adaptations to a narrow ecological niche, such as the primary tissue reservoirs of the human host. Adaptations may be further shaped by selection pressures such as herd immunity. Understanding the molecular evolution of GAS on multiple levels—short, intermediate, and long term—sheds insight on mechanisms of host-pathogen interactions, the emergence and spread of new clones, rational vaccine design, and public health interventions.

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Image of FIGURE 1

Transmission routes for GAS. From the throat, GAS can transmit via the respiratory route to a new host, where it either causes pharyngitis or persists in a quiescent carrier state. In a carrier state, the organism is presumed to be only weakly transmissible. Transmission from the throat to skin is relatively rare. From an impetiginous skin lesion, the organism can be transmitted by direct contact to the slightly damaged skin of a new host or to other damaged skin sites on the same host, causing multiple skin lesions. GAS can also be transmitted from a skin lesion to the throat of the same host, but it is widely assumed to enter a carrier state and is only weakly transmissible. From either the throat or skin, the organism can invade normally sterile deeper tissue, but this is rare relative to superficial infections.

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Image of FIGURE 2

M protein structure and pattern gene arrangements. Key features of M protein are shown, including the type-specific determinants, cell wall-spanning domain, and C repeat region. Chromosomal arrangement of and the flanking -like genes (, ) gives rise to five patterns, which form three main groupings (A-C, D, E). Transcription of and -like genes is positively regulated by Mga, which is encoded by , which lies immediately upstream of the region.

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Image of FIGURE 3

Structure of the pilus-encoding FCT region. Seven forms of the FCT region are shown. For pilus structural protein genes: , , and , backbone pilins; , , , , and , ancillary pilins. In FCT-2, , , and have sequence homology with , , and , respectively, although divergence is high ( 82 ). Pilin adhesins include FctX from FCT-1, AP1 from FCT-2, and Cpa from FCT-3 and FCT-4. Pilin subunits that anchor the pilus shaft to the cell wall include AP2 and FctB ( 249 ). Fibronectin-binding protein genes include (sometimes designated ), (sometimes designated ), and possibly others that remain to be classified.

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Image of FIGURE 4

Chromosomal map of the epidemiological marker genes of GAS. Open circles represent the seven core housekeeping genes used in MLST ( 104 ). The locus, when present, lies ∼15 kb upstream of . The FCT region, which encodes pilus structural proteins and pilus biosynthetic enzymes plus other adhesins and transcriptional regulators, ranges in size from ∼11 to 16 kb. The FCT region lies ∼250 to 300 kb from the region, on the opposite side of the origin of replication (). GAS genomes range in size from ∼1.8 to 1.9 Mb.

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Image of FIGURE 5

Model for evolutionary descent (CC407). goeBURST diagram of CC407, which includes single representatives of 41 STs and is based on data from www.pubmlst.org/spyogenes ( 105 ). Unless noted otherwise (orange shaded boxes), all isolates ( = 114) are and were recovered from (i) the 1990s through 2010s, (ii) Europe or North America, and (iii) URT infections or iGAS disease. For evolutionary analysis of (formerly PT4245 [ 250 ]) isolates based on the core genome sequence ( 31 , 111 ), clade 1 strain MGAS11027 is ST407, whereas clade 2 and epidemic clade 3 strains (MGAS23530 and MGAS27061, respectively) are ST101; the epidemic strain H293 from the United Kingdom is also ST101 ( 30 ). Note that ST407 corresponds to GAS with either or ( 105 ). Amino acid sequence identities among predicted FCT region gene products of ST407 (MGAS11027) and ST101 (H293, MGAS23530) strains (all ) via ClustalW alignments.

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Image of FIGURE 6

Trends in the distribution of epidemiological markers. An overview of the diversity and/or occurrence of epidemiological marker genes among three clinico-epidemiologic phenotype groupings of GAS. The relative distribution of FCT region forms is in accordance with one representative isolate for 94 unique types, as reported in reference 82; however, given the extensive HGT of and/or FCT genes to distant genetic backgrounds, the present analysis of the FCT region distribution may be far from complete.

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Epidemiological typing methods for group A streptococci

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Distribution of types among pattern groups for 170 types.

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Distribution of clusters relative to pattern groups, for 174 types

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Relationships between SOF/ and patterns and clades

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Relationships between pattern and T types for >20,000 GAS isolates

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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pattern assignments for GAS recovered in 29 population-based surveys for pharyngitis or impetigo

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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cluster and clade assignments for GAS recovered in 29 population-based surveys for pharyngitis or impetigo

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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type diversity within communities for the 29 population-based surveys for pharyngitis and impetigo

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018
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Relationships between pattern or cluster and type and subtype

Source: microbiolspec September 2018 vol. 6 no. 5 doi:10.1128/microbiolspec.CPP3-0009-2018

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