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Phase Variation of

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  • Authors: Jing Li1, Jing-Ren Zhang2
  • Editors: Vincent A. Fischetti3, Richard P. Novick4, Joseph J. Ferretti5, Daniel A. Portnoy6, Miriam Braunstein7, Julian I. Rood8
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing 100084, China; 2: Center for Infectious Disease Research, Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing 100084, China; 3: The Rockefeller University, New York, NY; 4: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 5: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 6: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 7: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 8: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
  • Received 28 December 2017 Accepted 20 November 2018 Published 08 February 2019
  • Jing-Ren Zhang, [email protected]
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  • Abstract:

    undergoes phase variation or spontaneous, reversible phenotypic variation in colony opacity, encapsulation, and pilus expression. The variation in colony opacity appears to occur in all strains, whereas the switches in the production of the capsule and pilus have been observed in several strains. This chapter elaborates on the variation in colony opacity since this phenomenon has been extensively characterized. produces opaque and transparent colonies on the translucent agar medium. The different colony phases are fundamentally distinct phenotypes in their metabolism and multiple characteristics, as exemplified by cell surface features and phenotypes in colonization and virulence. Opaque variants, which express more capsular polysaccharides and fewer teichoic acids, are more virulent in animal models of sepsis but colonize the nasopharynx poorly. In contrast, transparent variants, with fewer capsular polysaccharides and more teichoic acid, colonize the nasopharynx in animal models more efficiently but are relatively avirulent. Lastly, pneumococcal opacity variants are generated by differential methylation of the genome DNA variation. The reversible switch in the methylation pattern is caused by DNA inversions in three homologous genes of the colony opacity determinant () or SpnD39III locus, a conserved type I restriction-modification (RM) system. The gene encodes the sequence recognition subunit of the type I RM DNA methyltransferase. The combination of DNA inversion and differential methylation, a complex mechanism of phase variation, generates a mixed population that may allow for the selection of organisms with characteristics permissive for either carriage or systemic infection.

  • Citation: Li J, Zhang J. 2019. Phase Variation of . Microbiol Spectrum 7(1):GPP3-0005-2018. doi:10.1128/microbiolspec.GPP3-0005-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0005-2018
2019-02-08
2019-02-22

Abstract:

undergoes phase variation or spontaneous, reversible phenotypic variation in colony opacity, encapsulation, and pilus expression. The variation in colony opacity appears to occur in all strains, whereas the switches in the production of the capsule and pilus have been observed in several strains. This chapter elaborates on the variation in colony opacity since this phenomenon has been extensively characterized. produces opaque and transparent colonies on the translucent agar medium. The different colony phases are fundamentally distinct phenotypes in their metabolism and multiple characteristics, as exemplified by cell surface features and phenotypes in colonization and virulence. Opaque variants, which express more capsular polysaccharides and fewer teichoic acids, are more virulent in animal models of sepsis but colonize the nasopharynx poorly. In contrast, transparent variants, with fewer capsular polysaccharides and more teichoic acid, colonize the nasopharynx in animal models more efficiently but are relatively avirulent. Lastly, pneumococcal opacity variants are generated by differential methylation of the genome DNA variation. The reversible switch in the methylation pattern is caused by DNA inversions in three homologous genes of the colony opacity determinant () or SpnD39III locus, a conserved type I restriction-modification (RM) system. The gene encodes the sequence recognition subunit of the type I RM DNA methyltransferase. The combination of DNA inversion and differential methylation, a complex mechanism of phase variation, generates a mixed population that may allow for the selection of organisms with characteristics permissive for either carriage or systemic infection.

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Image of FIGURE 1
FIGURE 1

Overview of the major mechanisms behind reversible ON-and-OFF phase variation in bacteria.

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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Image of FIGURE 2
FIGURE 2

Genetic organization of the locus of ST556. The positions of three functional RM systems are indicated in the genome of ST556 according to a previous study ( 59 ). The gene order and other features in the locus are based on the published genome of the strain (accession no. CP003357) ( 122 ).

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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Image of FIGURE 3
FIGURE 3

Unique genetic configurations generated by DNA inversions in the locus. The genetic orientations of the and genes in the derivatives of forms S1 , S3 , and S4 are illustrated by arrows. Each DNA configuration is given an S number. The sequence compositions of the genes are indicated by colors. The inverted repeats (IRs) in three genes are represented by yellow (IR1), black (IR2), and white (IR3) arrowheads. The inverted DNA segments are marked by dashed lines.

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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Image of FIGURE 4
FIGURE 4

The unique methylome specified by each of the HsdS variants in the -locked strains. The sequence origins of each allele for the three genes are color-coded as shown in Fig. 3 . The methylated adenosine nucleotide in the DNA methylation motif identified by single-molecule real-time sequencing in each -locked strain is shown as a red character. The opaque and transparent phenotypes associated with the -locked strains in colony opacity are indicated in the right-hand panel. R = A or G, Y = T or C.

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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Image of FIGURE 5
FIGURE 5

Colony phenotypes associated with strain ST556 and its -locked derivatives. The colonies were prepared and photographed under a dissection microscope as described ( 52 ). The representative opaque and transparent colonies in the wild-type strain are indicated by blue and red arrowheads, respectively.

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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Image of FIGURE 6
FIGURE 6

Diagrammatic demonstration of the relationship between an epigenetic switch driven by DNA inversion in the locus and phase variation in colony opacity. The methylated and unmethylated adenine nucleotides in the DNA motif by the HsdS-associated methyltransferase are highlighted with red and blue characters, respectively. R = A or G, Y = T or C.

Source: microbiolspec February 2019 vol. 7 no. 1 doi:10.1128/microbiolspec.GPP3-0005-2018
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