Importance of prophages to evolution and virulence of bacterial pathogens

Abstract

Bacteriophages, or simply phages, are viruses infecting bacteria. With an estimated 10 ( 31) particles in the biosphere, phages outnumber bacteria by a factor of at least 10 and not surprisingly, they influence the evolution of most bacterial species, sometimes in unexpected ways. "Temperate" phages have the ability to integrate into the chromosome of their host upon infection, where they can reside as "quiescent" prophages until conditions favor their reactivation. Lysogenic conversion resulting from the integration of prophages encoding powerful toxins is probably the most determinant contribution of prophages to the evolution of pathogenic bacteria. We currently grasp only a small fraction of the total phage diversity. Phage biologists keep unraveling novel mechanisms developed by phages to parasitize their host. The purpose of this review is to give an overview of some of the various ways by which prophages change the lifestyle and boost virulence of some of the most dangerous bacterial pathogens.

Keywords: Clostridium; bacterial fitness; bacteriophage; biofilm; evolution; lysogenic conversion; prophage; sporulation; toxins; virulence.

Figure 1. Different lifestyles adopted by phages. True virulent phages will only follow the lytic cycle for their replication and will lead to the lysis of the host cell at the end of the cycle. Temperate phages have the choice to replicate through the lytic cycle like virulent phages, or they can opt for the lysogenic cycle. In most cases of lysogeny, the phage integrates its genome into the host bacterial chromosome and remains quiescent. The prophage DNA is replicated along with the bacterial chromosome and is transmitted to daughter cells. Lysogeny can sometimes have significant impacts on the host (lysogenic conversion). Under certain conditions, including various stresses causing DNA damages, the prophage is excised and initiates a lytic cycle. Some phages also adopt a pseudotemperate lifestyle, i.e., they generally do not integrate the chromosome of their host and replicate as linear or circular plasmids within the cytoplasm. Sometimes, the phage genome is lost during cell division and segregation, which is characterized by instability of the lysogens carrying these phages. Note that chronic infections by non-lytic phages (e.g., filamentous phages such as V. cholerae CTXϕ) are not represented on this figure.

Figure 2. Organization of the pathogenicity locus (PaLoc) in C. difficile. Arrowheads indicate a positive effect on the target and blunt ended lines indicate repression of the target. Phage ϕCD119 expresses a repressor that binds to the promoter region of TcdR, thereby repressing transcription of tcdR and hence, transcription of the toxin genes.