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Enterococcal Genetics

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  • Author: Keith E. Weaver1
  • Editors: Vincent A. Fischetti2, Richard P. Novick3, Joseph J. Ferretti4, Daniel A. Portnoy5, Miriam Braunstein6, Julian I. Rood7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069; 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.GPP3-0055-2018
  • Received 04 December 2018 Accepted 08 January 2019 Published 08 March 2019
  • Keith E. Weaver, [email protected]
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  • Abstract:

    The study of the genetics of enterococci has focused heavily on mobile genetic elements present in these organisms, the complex regulatory circuits used to control their mobility, and the antibiotic resistance genes they frequently carry. Recently, more focus has been placed on the regulation of genes involved in the virulence of the opportunistic pathogenic species and . Little information is available concerning fundamental aspects of DNA replication, partition, and division; this article begins with a brief overview of what little is known about these issues, primarily by comparison with better-studied model organisms. A variety of transcriptional and posttranscriptional mechanisms of regulation of gene expression are then discussed, including a section on the genetics and regulation of vancomycin resistance in enterococci. The article then provides extensive coverage of the pheromone-responsive conjugation plasmids, including sections on regulation of the pheromone response, the conjugative apparatus, and replication and stable inheritance. The article then focuses on conjugative transposons, now referred to as integrated, conjugative elements, or ICEs, and concludes with several smaller sections covering emerging areas of interest concerning the enterococcal mobilome, including nonpheromone plasmids of particular interest, toxin-antitoxin systems, pathogenicity islands, bacteriophages, and genome defense.

  • Citation: Weaver K. 2019. Enterococcal Genetics. Microbiol Spectrum 7(2):GPP3-0055-2018. doi:10.1128/microbiolspec.GPP3-0055-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0055-2018
2019-03-08
2019-08-25

Abstract:

The study of the genetics of enterococci has focused heavily on mobile genetic elements present in these organisms, the complex regulatory circuits used to control their mobility, and the antibiotic resistance genes they frequently carry. Recently, more focus has been placed on the regulation of genes involved in the virulence of the opportunistic pathogenic species and . Little information is available concerning fundamental aspects of DNA replication, partition, and division; this article begins with a brief overview of what little is known about these issues, primarily by comparison with better-studied model organisms. A variety of transcriptional and posttranscriptional mechanisms of regulation of gene expression are then discussed, including a section on the genetics and regulation of vancomycin resistance in enterococci. The article then provides extensive coverage of the pheromone-responsive conjugation plasmids, including sections on regulation of the pheromone response, the conjugative apparatus, and replication and stable inheritance. The article then focuses on conjugative transposons, now referred to as integrated, conjugative elements, or ICEs, and concludes with several smaller sections covering emerging areas of interest concerning the enterococcal mobilome, including nonpheromone plasmids of particular interest, toxin-antitoxin systems, pathogenicity islands, bacteriophages, and genome defense.

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FIGURE 1

Model for EutV- and EutX-mediated regulation of the regulon. In the absence of either EA or AdoCbl (–EA), EutV∼P dimers are not available to disrupt terminators upstream of genes. In the presence of EA but the absence of AdoCbl (+EA), the EutX riboswitch adopts a conformation that binds EutV∼P dimers, titrating them away from the gene terminators. In the presence of AdoCbl but the absence of EA (+AdoCbl), EutX adopts an alternative conformation that is not competent for binding EutV∼P dimers, but such dimers are absent due to the lack of EA. In the presence of both EA and AdoCbl (+AdoCbl, +EA), EutX is unable to bind EutV∼P dimers, which then interfere with termination in transcripts, allowing the genes to be transcribed. (Adapted from reference 87 .)

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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FIGURE 2

Organization of the VanA and VanB vancomycin resistance systems. Gene functions are color coded: green, sensory and regulatory; red, essential resistance genes; blue, auxiliary resistance genes. Detailed functions of each gene are described in the text. Green arrows show the position of the VanR inducible promoters. The percentage identity of the VanB genes to their VanA homologs is given below the individual VanB genes. Homologs have identical names in both systems except for the and ligases.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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FIGURE 3

Regulatory circuitry of the pheromone response. Events occurring at the cell surface. Important chromosomally encoded determinants are colored yellow with the exception of the pheromone itself, which is shown as blue circles. Plasmid-encoded determinants are color coordinated with their genes shown in panel B. The inhibitor peptide (ip) is shown as red circles and competitively inhibits pheromone binding to TraC. TraB inhibition of pheromone secretion is depicted here as sequestration, but may also involve peptide degradation. Events occurring at the DNA level. Binding of pheromone by TraA links events at the cell surface with events at the DNA level. A conformational change in TraA due to pheromone binding is indicated by the change in shape of the molecule and the change in dimerization state, although more subtle conformational changes are likely. Pheromone-free TraA binds Po and inhibits transcription. Direction of transcription from Po and Pa is indicated by the arrows. The antisense RNA, generalized to aR in this figure, stimulates termination at t1, indicated by the green arrow. Positive regulatory elements vary between different pheromone-responsive plasmids, and their mechanisms of inducing downstream transcription of the conjugation structural genes may also vary. For simplicity, the more common gene names and order are used. It should be noted that the gene order of the and genes are reversed in pAD1. The RepA gene is shown to orient the reader relative to Fig. 4 . Events at the RNA level. Relative levels of RNA produced from the Po and Pa promoters under uninduced (red) and induced (green) conditions are depicted by the sizes of the arrows.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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FIGURE 4

Genetic organization of a general pheromone-responsive plasmid replicon. Gene names are given as pAD1/pCF10. The stipled box within represents the origin of replication () to which the product binds. The lined boxes at each end of the operon represent the likely centromere-like sites to which the products bind and, with the product, direct plasmid partition. The organization of the region is blown up below the replicon. The arrowheads at each end of the locus marked P represent the promoters for the RNAI and RNAII transcripts. The extent and direction of transcription of the transcripts are shown above and below the genes for RNAII and RNAI, respectively. The gene is designated by the diagonally lined box, and the sequence of the peptide is shown at the bottom. DRa and DRb are direct repeats in the DNA sequence that provide complementarity between RNAI and RNAII when transcribed in opposite directions. Overlapping transcription at the bidirectional transcriptional terminator also provides complementarity.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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FIGURE 5

Model of RNAI-RNAII interaction. RNAI is the larger, black structure and RNAII is the smaller, blue structure. Stems, loops, and bulges are depicted in their approximate locations and sizes as determined by experimentation. The red stem-loop structure within RNAI sequesters the ribosome binding site and prevents translation until a complex is formed. The initial interaction occurs at a U-turn motif in the terminator loop of RNAI , followed by interaction between the complementary repeats in the 5′ end of each RNA . Since RNAII-mediated protection from the RNAI-encoded toxin occurs even when one of the repeats is mutated, the structure shown in panel C is apparently sufficient to prevent translation . Once complex formation is complete , the structure is extremely stable and perhaps due to the gap between the interacting repeats.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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FIGURE 6

Genetic organization of Tn and the relative positions of Int and Xis binding sites. Functions of Tn genes are color coded: blue, recombination; green and red, positive and negative regulation, respectively; yellow, tetracycline resistance; magenta, conjugation. Gene names and open reading frame numbers are shown above the individual genes. The origin of transfer is designated by the line between s and , labelled . Promoters and the direction of transcription are designated by labeled arrows below the gene line. Binding sites for the Int-C and Int-N DNA binding domains and Xis are designated by marked circles and triangles. Int and Xis binding sites are color coordinated with the genes shown in panel A.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0055-2018
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