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Genetics and Pathogenicity Factors of Group C and G Streptococci

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  • Author: Horst Malke1
  • Editors: Vincent A. Fischetti2, Richard P. Novick3, Joseph J. Ferretti4, Daniel A. Portnoy5, Miriam Braunstein6, Julian I. Rood7
    Affiliations: 1: Friedrich Schiller University Jena, Faculty of Biology and Pharmacy, D-07743 Jena, Germany, and University of Oklahoma Health Sciences Center, Department of Microbiology and Immunology, Oklahoma City, OK 73190; 2: The Rockefeller University, New York, NY; 3: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 4: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 5: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 6: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 7: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
  • Received 17 October 2017 Accepted 13 November 2018 Published 15 March 2019
  • Horst Malke, [email protected]
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  • Abstract:

    Of the eight phylogenetic groups comprising the genus , Lancefield group C and G streptococci (GCS and GGS, resp.) occupy four of them, including the Pyogenic, Anginosus, and Mitis groups, and one Unnamed group so far. These organisms thrive as opportunistic commensals in both humans and animals but may also be associated with clinically serious infections, often resembling those due to their closest genetic relatives, the group A streptoccci (GAS). Advances in molecular genetics, taxonomic approaches and phylogenomic studies have led to the establishment of at least 12 species, several of which being subdivided into subspecies. This review summarizes these advances, citing 264 early and recent references. It focuses on the molecular structure and genetic regulation of clinically important proteins associated with the cell wall, cytoplasmic membrane and extracellular environment. The article also addresses the question of how, based on the current knowledge, basic research and translational medicine might proceed to further advance our understanding of these multifaceted organisms. Particular emphasis in this respect is placed on streptokinase as the protein determining the host specificity of infection and the Rsh-mediated stringent response with its potential for supporting bacterial survival under nutritional stress conditions.

  • Citation: Malke H. 2019. Genetics and Pathogenicity Factors of Group C and G Streptococci. Microbiol Spectrum 7(2):GPP3-0002-2017. doi:10.1128/microbiolspec.GPP3-0002-2017.


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Of the eight phylogenetic groups comprising the genus , Lancefield group C and G streptococci (GCS and GGS, resp.) occupy four of them, including the Pyogenic, Anginosus, and Mitis groups, and one Unnamed group so far. These organisms thrive as opportunistic commensals in both humans and animals but may also be associated with clinically serious infections, often resembling those due to their closest genetic relatives, the group A streptoccci (GAS). Advances in molecular genetics, taxonomic approaches and phylogenomic studies have led to the establishment of at least 12 species, several of which being subdivided into subspecies. This review summarizes these advances, citing 264 early and recent references. It focuses on the molecular structure and genetic regulation of clinically important proteins associated with the cell wall, cytoplasmic membrane and extracellular environment. The article also addresses the question of how, based on the current knowledge, basic research and translational medicine might proceed to further advance our understanding of these multifaceted organisms. Particular emphasis in this respect is placed on streptokinase as the protein determining the host specificity of infection and the Rsh-mediated stringent response with its potential for supporting bacterial survival under nutritional stress conditions.

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Image of FIGURE 1

Phylogenetic relationships between the GCS and GGS species/subspecies included in Table 1 . The cladogram is based on 16S rRNA gene sequences employed in BLAST alignments (http://ncbi.nlm.nih.gov) using the 16S rRNA sequence of NZ131 as a query. The scale bar indicates 0.01 nucleotide substitutions per nucleotide position.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Image of FIGURE 2

Schematic representation of the domain organization of protein G, adapted from reference 102 . S, signal sequence; E, α-macroglobulin binding; A and B, human serum albumin binding; C, IgG binding; W, cell wall-associated region; M, cell membrane-associated region.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Image of FIGURE 3

Organization of the streptokinase-M protein gene region in the subsp. H46A chromosome based on references 71 and 183 . Arrows represent the genes and their orientation: , ribonucleotide reductase; , multigene regulator of GCS; , M protein; , 2′,3′-cyclic nucleotide 2′-phosphodiesterase, , bifunctional (p)ppGppase and (p)ppGpp synthetase; , -tyrosyl-tRNA deacylase; , streptokinase; , leucine-rich protein, now recognized as a transcriptional regulator of the PucR family featuring a C-terminal helix-turn-helix domain; , ATP binding cassette transporter; , α-glucosidase.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Image of FIGURE 4

Primary structural features of the 5′-untranslated region 47 nucleotides upstream of the / ATG translational start codon. Additionally indicated are the -10 regions of the tandem P1 and P2 promoters (underlined), including (in red) the TG nucleotide extension of P1, the target sequence of CovR (in green) with the consensus binding site underlined, the FasX hybridization site (in blue), the two major transcription initiation sites (stars), and the mRNA ribosome binding sequence (RBS, underlined). These features are based on references 188 , 190 , 196 , and 199 .

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Image of FIGURE 5

Sequence comparison of and σ factors between region 2.4 and the start of region 3. Identical and similar amino acids are marked by asterisks and dots, respectively. The residues identified in ( 191 ) as contacting the TG extension of the -10 P1 promoter hexamer are highlighted in red.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Image of FIGURE 6

Structure of Rel1-385. ppGpp Hydrolase-OFF/synthetase-ON conformation in complex with Mn (blue sphere) and GDP (stick rendering). The hydrolase domain is highlighted in green α-helices and blue β-strands, the synthetase domain is in yellow α-helices and orange β-strands, and the central 3-helix bundle is red. Part of the substrate binding cleft comprising the hydrolase site (downregulated) is disordered (red arrow). The small synthetase/hydrolase interdomain contact interface involved in signal transmission is labeled with a red star. Hydrolase-ON/synthetase-OFF conformation in complex with Mn, ppG2′:3′p (which locks the enzyme in the hydrolase-ON/synthetase-OFF conformation) and GDP. The coloring and rendering schemes are the same as for panel A. The disordered synthetase site (downregulated) is illustrated as dashed lines with a red arrow. Primary and secondary structure of Rel1-385. The secondary structure is color-coded as in panels A and B. Unique secondary structure assignments for panel A are placed immediately below the corresponding assignments for panel B. Residues absolutely conserved throughout the mono- and bifunctional RelA and SpoT homologs are underlaid with blue boxes. Residues conserved in SpoT and the bifunctional enzymes but mutated in the hydrolase-incompetent RelA homologs are underlaid with red boxes. Upright and inverted black triangles above the sequence indicate residues which when substituted experimentally by missense mutations lead to defective hydrolase and synthetase activities, respectively. Reproduced from reference 251 , with permission. Semitransparent surface rendering of the bifunctional N-terminal half of Rel1-385 based on its 2.1-Å X-ray structure ( 251 ). The hydrolysis site (underlaid in green) binding the ppGpp analog ppG2′-3′p (stick rendering) is separated by the central 3-helix bundle and about 30 Å away from the synthesis site (underlaid in red) binding GDP (stick rendering). The image was generated by Tanis Hogg with the molecular graphics program PyMOL (Warren L. DeLano Scientific, Palo Alto, CA) and kindly provided for publication.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Hypothetical metabolic mechanisms explaining differential bacterial survival rates under stringent and relaxed conditions based on data reviewed in reference 246 and references therein.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017
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Properties of Lancefield group C and G species

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0002-2017

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