Naturally competent bacteria and their genetic parasites-a battle for control over horizontal gene transfer?

Abstract

Host-mediated natural competence for transformation of DNA and mobile genetic element (MGE)-driven conjugation and transduction are key modes of horizontal gene transfer. While these mechanisms are traditionally believed to shape bacterial evolution by enabling the acquisition of new genetic traits, numerous studies have elucidated an antagonistic relationship between natural transformation and MGEs. A new role of natural transformation as a chromosome-curing mechanism has now been proposed. Experimental data, along with mathematical models, suggest that transformation can eliminate deleterious MGEs. Supporting this hypothesis, MGEs have been shown to use various mechanisms to decrease or block transformability, such as disrupting competence genes, regulating the development of competence, hindering DNA uptake machinery, producing DNases that target the exogenous (transforming) DNA, and causing lysis of competent cells. A few examples of synergistic relationships between natural transformation and MGEs have also been reported, with natural transformation facilitating MGE transfer and phages enhancing transformation by supplying extracellular DNA through lysis and promoting competence via kin discrimination. Given the complexity of the relationships between natural transformation and MGEs, the balance between antagonism and synergy likely depends on specific selection pressures in a given context. The evidence collected here indicates a continuous conflict over horizontal gene transfer in bacteria, with semiautonomous MGEs attempting to disrupt host-controlled DNA acquisition, while host competence mechanisms work to resist MGE interference.

Keywords: genetic diversity; mobile genetic element; natural competence; phage; transformation.

Figure 1.

Schematic representation of DNA uptake machinery in diderms and monoderms. Type IV pilus components (in diderms) and competence pilus components (in monoderms) are shown in blue; DNA uptake and translocation proteins are shown in orange; and DNA binding and recombination proteins are shown in red. Proteins shown in bold were shown to be targeted by mobile genetic elements. Abbreviations: OM, outer membrane; PG, peptidoglycan; IM, inner membrane; dsDNA, double stranded DNA; and ssDNA, single stranded DNA. This figure was adapted from (Vesel and Blokesch 2021).

Figure 2.

Illustration of the natural transformation process leading to MGE acquisition or deletion. The competence apparatus enables the internalization of ssDNA (either containing an MGE or not). This ssDNA is then integrated into the bacterial genome through homologous recombination, resulting in either the acquisition or loss of MGE. Abbreviation: ssDNA, single stranded DNA.

Figure 3.

Schematic representation of MGE-driven mechanism that counteract natural transformation. These mechanisms result in: (1) disruption of competence genes, (2) repression or lack of competence gene expression, (3) blocking of the competence apparatus, (4) degradation of transforming DNA, or (5) lysis of competent cells. Abbreviations: tDNA, transforming DNA, dsDNA, double stranded DNA; ssDNA, single stranded DNA; and TIR, transformation-inhibiting factor.

Figure 4.

Depiction of examples, where natural competence promotes the MGEs spread. In the donor cell, the competence protein RecA promotes plasmid multimerization and induces SOS response-driven cell lysis, both of which increase the efficiency of MGEs spread. In the recipient cell, transformation enables the uptake of MGEs (either as plasmid or MGEs carried on the chromosome or plasmid). In the next step, competence proteins are involved in the circularization of plasmid DNA or in the integration of MGEs into the chromosome through transposition or homologous recombination. Abbreviations: ssDNA, single stranded DNA and TSD, target site duplication.

Figure 5.

Illustration of examples, where MGEs positively impact natural transformation. MGEs can enhance natural transformation through (i) phage-driven cell lysis during the lytic cycle, which increases the availability of transforming DNA; (ii) GTAs-driven competence induction and production of competence proteins, which enable GTAs uptake; and (iii) induction of competence in the recipient strain through nonkin interactions, resulting in increased cell envelope stress in the donor strain. Abbreviation: GTA, gene transfer agent.