CRISPR-based herd immunity can limit phage epidemics in bacterial populations

Payne, Pavel; Geyrhofer, Lukas; Barton, Nicholas H.; Bollback, Jonathan P.

doi:10.7554/elife.32035

Cited by 36 publications

(37 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Payne et al . (55) demonstrated that cross-protection against phage T7 can occur between two strains of E. coli , where one harbored a CRISPR-based resistance. Cross-protection was observed both in liquid and on a bacterial lawn.…”

Section: Discussionmentioning

confidence: 99%

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Testa

Berger

Piccardi

et al. 2019

Preprint

View full text Add to dashboard Cite

Bacterial viruses, or phage, play a key role in shaping natural 1 microbial communities. Yet much research on bacterial-phage 2 interactions has been conducted in liquid cultures involving sin-3 gle bacterial strains. Critically, phage often have a very narrow 4 host range meaning they can only ever target a subset of strains 5 in a community. Here we explore how strain diversity affects 6 the success of lytic phage in structured communities. In par-7 ticular, we infect a susceptible Pseudomonas aeruginosa strain 8 PAO1 with lytic phage Pseudomonas 352 in the presence versus 9 absence of an insensitive P. aeruginosa strain PA14, in liquid cul-10 ture versus colonies growing on agar. We find that competition 11 between the two bacterial strains reduces the likelihood of the 12 susceptible strain evolving resistance to the phage. This result 13 holds in liquid culture and in colonies. However, while in liq-14 uid the phage eliminate the whole sensitive population, colonies 15 contain refuges wherein bacteria can remain sensitive yet es-16 cape phage infection. These refuges form mainly due to reduced 17 growth in colony centers. We find little evidence that the pres-18 ence of the insensitive strain provides any additional protection 19 against phage. Our study reveals that living in a spatially struc-20 tured population can protect bacteria against phage infection, 21 while the presence of competing strains may instead reduce the 22 likelihood of evolving resistance to phage, if encountered. 23 Bacterial colony | resistance | evolution | microbial communities | population 24 dynamics | spatial structure | phage therapy 25 Correspondence: sara.mitri@unil.ch 26 82 survival rate compared to planktonic bacteria (25), particu-83 larly when exposed to antibiotics and importantly, also to 84 phage (26). More generally, phage population dynamics dif-85 fer radically between liquid bacterial cultures and bacteria 86 growing on solid surfaces (27). 87 Here we show that both of these factors -the presence of 88 other strains, and spatial structure -separately and combined 89 affect the outcome of phage predation on the pathogen Pseu-90 Testa et al. | bioRχiv | February 15, 2019 | 1-10In particular, we target P. aeruginosa strain PAO1 with Pseu-92 domonas phage 352 to which it is sensitive, in the presence 93 and absence of a second strain, P. aeruginosa PA14 that is in-94 sensitive to the phage. Since phage are so specific, we believe 95 the choice of a closely-related phage-insensitive strain to be 96 a realistic one. We compare the outcome for PAO1 in a well-97 mixed liquid environment and a structured biofilm (colony) 98 growing on a solid agar surface. 99 We find that in liquid, competition between the two strains 100 can reduce the population size of the target strain PAO1, giv-101 ing a competitive advantage to the phage and eliminating 102 PAO1 without the emergence of resistance. Indeed, evolv-103 ing resistance to the phage was the only way for PAO1 to 104 survive phage attack in liquid. In contrast, in a biofilm...

show abstract

Section: Discussionmentioning

confidence: 99%

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Testa

Berger

Piccardi

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Analogously, the spatial structure of immune responses mediated by IFN and other cytokines can be determined by the diffusion of signaling molecules and the effect of these signals in receptor cells [12]. In addition to infection and immunity, diffusion-reaction models have been used for addressing a variety of eco-evolutionary questions such as, for instance, how bacterial CRISPR limits viral spread [13] and how spatial obstacles perturb population expansion fronts and promote random genetic drift [14].…”

Section: Introductionmentioning

confidence: 99%

The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model

Segredo-Otero

Sanjuán

2020

PLoS Comput Biol

View full text Add to dashboard Cite

show abstract

“…235 5A & B), which parallels the decline in phage population sizes over time in the same 236 treatments (regression of ln pfu ml -1 over dpi: β [95% CI] = -2.58 [-3.23, -1.84], t(2) 114 = -7.64, p = 7.27 x 10 -12 ). These data suggest that susceptible hosts are 238 protected by population-level CRISPR diversity, and that this protection is mediated 239 by a reduced ability of phage to replicate on increasingly dilute susceptible hosts 240 (Payne et al, 2018) (Figure S1). affected by -evolutionary emergence.…”

mentioning

confidence: 96%

Diversity in CRISPR-based immunity protects susceptible genotypes by restricting phage spread and evolution

Common

Walker‐Sünderhauf

Houte

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractDiversity in host resistance often associates with reduced pathogen spread. This may result from ecological and evolutionary processes, likely with feedback between them. Theory and experiments on bacteria-phage interactions have shown that genetic diversity of the bacterial adaptive immune system can limit phage evolution to overcome resistance. Using the CRISPR-Cas bacterial immune system and lytic phage, we engineered a host-pathogen system where each bacterial host genotype could be infected by only one phage genotype. With this model system, we explored how CRISPR diversity impacts the spread of phage when they can overcome a resistance allele, how immune diversity affects the evolution of the phage to increase its host range, and if there was feedback between these processes. We show that increasing CRISPR diversity benefits susceptible bacteria via a dilution effect, which limits the spread of the phage. We suggest that this ecological effect impacts the evolution of novel phage genotypes, which then feeds back into phage population dynamics.

show abstract

CRISPR-based herd immunity can limit phage epidemics in bacterial populations

Cited by 36 publications

References 75 publications

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model

Diversity in CRISPR-based immunity protects susceptible genotypes by restricting phage spread and evolution

Contact Info

Product

Resources

About