Methylation Warfare: Interaction of Pneumococcal Bacteriophages with Their Host

• Published in: Journal of bacteriology 2019-10, Vol.201 (19), p.1
• Main Authors: Furi, Leonardo, Crawford, Liam A, Rangel-Pineros, Guillermo, Manso, Ana S, De Ste Croix, Megan, Haigh, Richard D, Kwun, Min J, Engelsen Fjelland, Kristine, Gilfillan, Gregor D, Bentley, Stephen D, Croucher, Nicholas J, Clokie, Martha R, Oggioni, Marco R
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacteriology; Bacteriophages - genetics; Bacteriophages - physiology; Biosynthesis; Deoxyribonucleic acid; DNA; DNA Methylation; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Viral; Gene regulation; Genomes; Host-Pathogen Interactions; Humans; Lysogeny; Methylation; Mouth - microbiology; Nucleotides; Phages; Restriction-modification; Sequence Analysis, RNA; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - virology; Transcription; Viral Proteins - genetics; Viruses; Warfare
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.00370-19

Virus-host interactions are regulated by complex coevolutionary dynamics. In , phase-variable type I restriction-modification (R-M) systems are part of the core genome. We hypothesized that the ability of the R-M systems to switch between six target DNA specificities also has a key role in preventing the spread of bacteriophages. Using the streptococcal temperate bacteriophage SpSL1, we show that the variants of both the SpnIII and SpnIV R-M systems are able to restrict invading bacteriophage with an efficiency approximately proportional to the number of target sites in the bacteriophage genome. In addition to restriction of lytic replication, SpnIII also led to abortive infection in the majority of host cells. During lytic infection, transcriptional analysis found evidence of phage-host interaction through the strong upregulation of the nucleotide biosynthesis regulon. During lysogeny, the phage had less of an effect on host gene regulation. This research demonstrates a novel combined bacteriophage restriction and abortive infection mechanism, highlighting the importance that the phase-variable type I R-M systems have in the multifunctional defense against bacteriophage infection in the respiratory pathogen With antimicrobial drug resistance becoming an increasing burden on human health, much attention has been focused on the potential use of bacteriophages and their enzymes as therapeutics. However, the investigations into the physiology of the complex interactions of bacteriophages with their hosts have attracted far less attention, in comparison. This work describes the molecular characterization of the infectious cycle of a bacteriophage in the important human pathogen and explores the intricate relationship between phase-variable host defense mechanisms and the virus. This is the first report showing how a phase-variable type I restriction-modification system is involved in bacteriophage restriction while it also provides an additional level of infection control through abortive infection.