The coevolutionary dynamics between bacteria with CRISPR-Cas immunity and their lytic phages
Date: 11 March 2019
University of Exeter
Masters by Research in Biological Sciences
Bacteriophage (phage), viruses of bacteria, are the most abundant and diverse biological entities on Earth. There are an estimated 10³⁰ phages in the biosphere; collectively they outnumber their prokaryotic hosts tenfold, and they are thought to destroy up to half of the World’s bacteria every 48 hours. Yet, despite the ubiquity of ...
Bacteriophage (phage), viruses of bacteria, are the most abundant and diverse biological entities on Earth. There are an estimated 10³⁰ phages in the biosphere; collectively they outnumber their prokaryotic hosts tenfold, and they are thought to destroy up to half of the World’s bacteria every 48 hours. Yet, despite the ubiquity of phage and the influence they exert over bacterial populations, we lack a detailed understanding of the complex bacteria-phage interactions that govern the coexistence of both species. Lytic phages – which require cell death to complete their life cycle – impose continuous selection pressures on bacteria to evolve resistance or face extinction. Likewise, increasing bacterial resistance creates strong selection pressures on phage to evolve greater infectivity. These reciprocal adaptations can lead to coevolution, which has profound consequences for the genetic diversity and evolutionary trajectories of both species. One such phage-resistance mechanism in bacteria is CRISPR-Cas (clustered regularly interspaced short palindromic repeats - and associated Cas proteins); a heritable, adaptive immune system that is found in approximately half of all bacteria. CRISPR provides immunity against phages by incorporating phage-derived ‘spacer’ sequences into CRISPR loci on the bacterial genome. Transcriptions of these spacers can recognise and cleave complementary DNA from invading phage genotypes, but phage can ‘escape’ CRISPR by mutating the regions targeted by the spacers, enabling them to re-infect previously-resistant bacteria and potentially leading to coevolution. To date, very few CRISPR-phage systems have been studied in detail, but two of the best-known systems; Pseudomonas aeruginosa and Streptococcus thermophilus, show great variation in their efficacy at preventing phage infections. Whilst phage are rapidly driven extinct in P. aeruginosa, they can coexist over long periods in S. thermophilus; but it is unclear whether this phage persistence is due to coevolution, and if so, what kind of coevolutionary dynamics are associated with this system. In this thesis, I examine P. aeruginosa and S. thermophilus together with their lytic phages in a coevolutionary context to better understand the role of coevolution in CRISPR-phage interactions. I first explain how the diversity of CRISPR spacers generated in P. aeruginosa rapidly drives phage extinct, but that phage can become locally adapted when CRISPR spacer diversity is low. I then present the first empirical evidence of CRISPR-phage coevolution in S. thermophilus and show that coevolution follows an arms race dynamic in this system. I conclude by discussing the importance of CRISPR spacer diversity in determining the outcome of CRISPR-phage interactions and how low spacer diversity can lead to coevolution and local adaptation.
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