Social behavior and decision making in bacterial conjugation

Abstract

Bacteria frequently acquire novel genes by horizontal gene transfer (HGT). HGT through the process of bacterial conjugation is highly efficient and depends on the presence of conjugative plasmids (CPs) or integrated conjugative elements (ICEs) that provide the necessary genes for DNA transmission. This review focuses on recent advancements in our understanding of ssDNA transfer systems and regulatory networks ensuring timely and spatially controlled DNA transfer (tra) gene expression. As will become obvious by comparing different systems, by default, tra genes are shut off in cells in which conjugative elements are present. Only when conditions are optimal, donor cells-through epigenetic alleviation of negatively acting roadblocks and direct stimulation of DNA transfer genes-become transfer competent. These transfer competent cells have developmentally transformed into specialized cells capable of secreting ssDNA via a T4S (type IV secretion) complex directly into recipient cells. Intriguingly, even under optimal conditions, only a fraction of the population undergoes this transition, a finding that indicates specialization and cooperative, social behavior. Thereby, at the population level, the metabolic burden and other negative consequences of tra gene expression are greatly reduced without compromising the ability to horizontally transfer genes to novel bacterial hosts. This undoubtedly intelligent strategy may explain why conjugative elements-CPs and ICEs-have been successfully kept in and evolved with bacteria to constitute a major driving force of bacterial evolution.

Keywords: bacterial conjugation; conjugative plasmids (CP); gene regulatory networks; horizontal gene transfer (HGT); integrative conjugative elements (ICE); mobile genetic elements.

Figure 1

Conjugative plasmids (CPs) and integrative conjugative elements (ICEs). Events leading to horizontal transfer of CPs (A) or ICEs (B) are shown schematically. Before transfer can occur, tra genes must be expressed and a T4SS assembled. After cell-cell contact formation, transfer competent donor cells initiate a rolling circle type replication from circular dsDNA and translocate ssDNA via the T4S machinery into recipient cells. dsDNA is then reconstituted in the recipient (dotted inner circle). (A) CPs can autonomously replicate due to the presence of rep genes. (B) ICEs replicate as integrated elements with the host chromosome (green lines), integration and excision is mediated by int/xis genes required for integration and excision by site-specific recombination via attachment sites (vertical bars). After excision and before integration, ICEs are present in a plasmid-like dsDNA form.

Figure 2

Two models for the development of transfer competence in single cells (A) and populations (B) are shown. In single cells (A) tra genes are turned ON by a variety of stimuli. A positive feedback loop ensures that, once initiated, cells proceed to transfer competence, involving formation of the Dtr complex and assembly of the T4S apparatus. In transfer competent cells, tra genes are switched OFF, mediated by a negative feedback loop. Eventually, transfer competence is lost by transition to unfavorable conditions. In unstructured, well-mixed populations (B) only a few donor cells (indicated by + signs) develop transfer competence, thereby minimizing the fitness cost for the population. For examples, detailed descriptions and discussions, the reader is referred to the section “How and when to turn DNA transfer genes ON” in the main text of this review.