Bacterial transformation: distribution, shared mechanisms and divergent control

Journal name:
Nature Reviews Microbiology
Year published:
Published online


Natural bacterial transformation involves the internalization and chromosomal integration of DNA and has now been documented in ~80 species. Recent advances have established that phylogenetically distant species share conserved uptake and processing proteins but differ in the inducing cues and regulatory mechanisms that are involved. In this Review, we highlight divergent and common principles that govern the transformation process in different bacteria. We discuss how this cumulative knowledge enables the prediction of new transformable species and supports the idea that the main role of internalized DNA is in the generation of genetic diversity or in chromosome repair rather than in nutrition.

At a glance


  1. Phylogenetic distribution of naturally transformable species, the DNA-uptake protein ComEC and the DNA-processing protein DprA.
    Figure 1: Phylogenetic distribution of naturally transformable species, the DNA-uptake protein ComEC and the DNA-processing protein DprA.

    a | Phylogenetic tree of naturally transformable species (which was generated as described in Ref. 85), on the basis of a collection of 137 conserved protein sequences. The numbers refer to species that are detailed in Supplementary information S1 (table). The parametric bootstrap167 values were greater than 96% for all branches except those at the origin of clades 16–20 (66%) and 41–42 (50%). b | Phylogenetic analysis of DprA in naturally transformable species. The upper panel shows a schematic of Streptococcus pneumoniae and Escherichia coli DprA proteins, with the known domains indicated. The centre panel shows a phylogenetic tree that was constructed using subsequences from the pfam02481 domain. The parametric bootstrap167 values were greater than 90% for all branches except those at the origin of clades 14–15 (87%), 13–17 (75%) and 30–31 (70%). In the lower panel, a comparison of the rate of evolution of DprA sequences and species evolution is shown. The evolutionary distances were computed as described in Ref. 85 (each blue dot corresponds to the distance computed for a given species pair and the blue colour gradually changes to red when spot density increases). The data suggest that DprA evolves at a rate that is threefold higher than the rate of species evolution. c | Phylogenetic analysis of ComEC in naturally transformable species. The upper panel shows a schematic of S. pneumoniae ComEC protein, with the known domains indicated. The centre panel shows a phylogenetic tree constructed using subsequences from the pfam03772 domain. The parametric bootstrap167 values were greater than 92% for all branches except those at the origin of clades 5–20 (89%), 13–20 (74%), 31–32 (71%), 42–43 (77%), 49–57 (86%), and 54–57 (80%). The lower panel shows a comparison of the rate of evolution of ComEC sequences and species evolution, which suggests that ComEC evolves at a rate that is six-fold higher than the rate of species evolution. The DprA and ComEC trees were computed using PhyML from a multiple alignment obtained using the MUSCLE program and trimmed with the trimAl program, as described in Ref. 86; 242 and 168 informative sites, respectively, were used for tree computation. The Le and Gascuel(LG) model of sequence evolution with a Γ-correction (which incorporates four categories of evolutionary rates) was used and the shape parameter and the proportion of invariant sites that were estimated from the data were selected by the ProtTest3 program86. The branch supports were estimated using 100 replicates of non-parametric bootstrap. e, extension of Rossman fold; RF, Rossman fold; SAM, sterile alpha motif.

  2. An overview of the transformation process.
    Figure 2: An overview of the transformation process.

    The key steps of transformation in Gram-positive and Gram-negative species are shown. The DNA-uptake machinery generally comprises a transformation pilus (Tfp), which consists mainly of ComGC subunits in Gram-positive bacteria and captures exogenous double-stranded DNA (dsDNA), the DNA receptor ComEA and the transmembrane pore ComEC. In Streptococcus pneumoniae, the EndA nuclease receives DNA from the DNA receptor ComEA and degrades one DNA strand, whereas unidentified nucleases (or strand-separating proteins) generate single-stranded DNA (ssDNA) for uptake in other species. In Firmicutes, ssDNA internalization through ComEC is presumably driven by the ATP-dependent translocase ComFA. In Gram-negative bacteria, such as Neiserria gonorrhoeae, the PilQ secretin channel enables the pilus (which is mainly composed of PilE subunits) to cross the outer membrane and dsDNA is transported across the outer membrane through PilQ. In both Gram-positive and Gram-negative cells, additional proteins are required for DNA uptake (for example, the ComGA and ComGB proteins of Firmicutes). A homologue of the ComFA translocase might be present in Gram-negative bacteria, but this is currently unclear. Internalized ssDNA is presumably bound by DprA (DNA processing protein A), which recruits the recombinase RecA. RecA polymerizes on ssDNA and promotes a homology search along chromosomal DNA, followed by strand exchange. The transformation heteroduplex that forms can be a fully homologous double-stranded recombination intermediate, or if the imported DNA contains heterologous sequences (such as a pathogenicity island) flanked by homology, a recombination intermediate with a single-stranded loop is formed. If heterologous donor DNA is unmethylated (light grey circles), this DNA remains fully unmethylated in the recipient chromosome after replication. The methylation and restriction activities of the restriction–modification (R–M) system compete (dashed arrows) for access to this sensitive DNA, and restriction can kill transformants and limit heterologous transformation. PG, peptidoglycan.

  3. Divergent competence regulatory cascades.
    Figure 3: Divergent competence regulatory cascades.

    a | Competence genes can be regulated by alternative σ factors (for example, σX in streptococci such as Streptococcus pneumoniae), transcription factors (such as ComK in bacilli such as Bacillus subtilis) and transcription co-regulators (such as the cAMP receptor protein (CRP) cofactor TfoX in Vibrio cholerae). Although TfoX directly regulates most of the com genes in V. cholerae, it indirectly activates comEA and comEC by regulating the expression of qstR60. b | Distribution of the two distinct two-component systems that regulate competence in streptococci: ComDE and ComRS. The ComDE system is present in S. pneumoniae and the Streptococcus mitis and Streptococcus anginosus groups, and ComRS is present in the Streptococcus mutans, Streptococcus salivarius, Streptococcus bovis and Streptococcus pyogenes groups. Both of these systems regulate expression of the central competence regulator σX. Lactococcus lactis was used as an outgroup in the distribution analysis. Filled circles with white digits indicate species that have been shown to be naturally transformable. Scale bar represents phylogenetic distance. For information on the genomes and methods used to create the tree, see Ref. 85. Two additional transformable species included here are Streptococcus infantarius (species NC_016826, genome CJ18) and Streptococcus macedonicus (species NC_016749, genome ACA-DC 198)39. Part b is modified, with permission, from Ref. 85 © (2013) Proceedings of the National Academy of Sciences, USA.


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Author information


  1. Centre National de la Recherche Scientifique, LMGM-UMR5100, F-31000 Toulouse, France.

    • Calum Johnston,
    • Bernard Martin,
    • Gwennaele Fichant,
    • Patrice Polard &
    • Jean-Pierre Claverys
  2. Université de Toulouse, UPS, Laboratoire de Microbiologie et Génétique Moléculaires, F-31000 Toulouse, France.

    • Calum Johnston,
    • Bernard Martin,
    • Gwennaele Fichant,
    • Patrice Polard &
    • Jean-Pierre Claverys

Competing interests statement

The authors declare no competing interests.

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Author details

  • Calum Johnston

    Calum Johnston is a postdoctoral researcher at the Laboratoire de Génétique et Microbiologie Moléculaires, Toulouse, France. Having obtained a Ph.D. from the University of Glasgow, UK, studying pneumococcal pathogenesis, he joined the team of Jean-Pierre Claverys in 2008. In this team, he studies the regulation and mechanisms that are involved in transformation using the model organism Streptococcus pneumoniae.

  • Bernard Martin

    Bernard Martin is Professor of Molecular Genetics at the University Paul Sabatier, Toulouse, France. He has worked for more than 30 years with Jean-Pierre Claverys in the 'Pneumococcal transformation' team, studying the regulation and mechanisms that are involved in the transformation of Streptococcus pneumoniae.

  • Gwennaele Fichant

    Gwennaele Fichant is Professor of Bioinformatics at the University Paul Sabatier, Toulouse, France. She received a Ph.D. in bioinformatics at the Laboratoire de Biométrie, Biologie Evolutive, Lyon, France. Her interests include the development of computer programs for the prediction of biological objects. Her more recent work involves the prediction and representation of biological integrated systems in bacteria as well as their phylogenomic analyses.

  • Patrice Polard

    Patrice Polard is a senior scientist at the Laboratoire de Génétique et Microbiologie Moléculaires, Toulouse, France, and recently became Co-director of the 'Pneumococcal transformation' team with Jean-Pierre Claverys. He has previously worked on transposition as well as replication fork restart in Bacillus subtilis. The 'pneumococcal transformation' team currently studies the regulation of competence for genetic transformation and the mechanisms of uptake and processing of transforming DNA in Streptococcus pneumoniae.

  • Jean-Pierre Claverys

    Jean-Pierre Claverys is a bacterial geneticist. He is Co-director of the 'Pneumococcal transformation' team with Patrice Polard. His main interests currently include investigating the signals that trigger competence and the changes in physiology that occur in competent Streptococcus pneumoniae cells as a means of understanding the roles of competence in the biology of this human pathogen. He was Head of the Laboratoire de Microbiologie et Génétique Moléculaires, CNRS-Université Paul Sabatier, Toulouse, France, from 2002 to 2006.

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    Naturally transformable bacterial species

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