Bacteriophages benefit from generalized transduction

Abstract

Temperate phages are bacterial viruses that as part of their life cycle reside in the bacterial genome as prophages. They are found in many species including most clinical strains of the human pathogens, Staphylococcus aureus and Salmonella enterica serovar Typhimurium. Previously, temperate phages were considered as only bacterial predators, but mounting evidence point to both antagonistic and mutualistic interactions with for example some temperate phages contributing to virulence by encoding virulence factors. Here we show that generalized transduction, one type of bacterial DNA transfer by phages, can create conditions where not only the recipient host but also the transducing phage benefit. With antibiotic resistance as a model trait we used individual-based models and experimental approaches to show that antibiotic susceptible cells become resistant to both antibiotics and phage by i) integrating the generalized transducing temperate phages and ii) acquiring transducing phage particles carrying antibiotic resistance genes obtained from resistant cells in the environment. This is not observed for non-generalized transducing temperate phages, which are unable to package bacterial DNA, nor for generalized transducing virulent phages that do not form lysogens. Once established, the lysogenic host and the prophage benefit from the existence of transducing particles that can shuffle bacterial genes between lysogens and for example disseminate resistance to antibiotics, a trait not encoded by the phage. This facilitates bacterial survival and leads to phage population growth. We propose that generalized transduction can function as a mutualistic trait where temperate phages cooperate with their hosts to survive in rapidly-changing environments. This implies that generalized transduction is not just an error in DNA packaging but is selected for by phages to ensure their survival.

Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages

“… 48 Antibiotic resistance genes can be located chromosomally or in plasmids. 47 Generalized transduction of low- and high-copy plasmids has previously been shown with Salmonella phage P22, Bacillus phage SPP2 and E. coli phage Mu. 9–12 In addition, some strains harbour certain P1 phage derivatives that remain as plasmids during their life cycle without being integrated as prophages.…”

Causes and consequences of bacteriophage diversification via genetic exchanges across lifestyles and bacterial taxa

“…In the mammalian gut, for instance, temperate phages seem to be more prevalent (5), while most intracellular and many environmental bacteria lack prophages (6), and are thus presumably rarely infected by temperate phages. Phages also drive horizontal gene transfer among bacteria by transduction (3), which may disseminate virulence factors (7) and antibiotic resistance (8).…”

“…Lysogeny is highly relevant for the evolution of bacteria, since half of the bacterial genomes have at least one prophage and some have up to 20 prophages (Touchon et al 2016). Phages also drive horizontal gene transfer among bacteria by transduction (Touchon et al 2017), which may disseminate virulence factors (Penadés et al 2015) and antibiotic resistance (Fillol-Salom et al 2019).…”

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

“…It is important to note that transduction would be an inconsequential process if it did not provide benefits to both bacteria and bacteriophages. Observations of the competitive advantages which lysogens have over prophage-lacking competitors supports the notion that the presence of prophages may function as a mutualistic trait [111,112]. Once considered as bacterial parasites which silently persist within bacteria, prophages are now understood to have a symbiotic relationship with their bacterial hosts [113].…”

“…Following this, headful packaging and assembly may initiate on some genomes and lead to the transfer of viral and bacterial chromosomal DNA to other bacteria, while other phage genomes may simultaneously continue with normal phage maturation [110]. Due to its efficient transfer of several hundred kilobases of genetic material [110], it is believed that lateral transduction is a leading force in the rapid evolution of bacteria as opposed to the comparatively smaller amounts of genetic material (~40 kb) transferred through generalized transduction, for example [96,111].…”