Phage-Bacterial Dynamics with Spatial Structure: Self Organization around Phage Sinks Can Promote Increased Cell Densities

Bull, James J.; Christensen, Kelly A.; Scott, Carly; Jack, Benjamin R.; Crandall, Cameron J.; Krone, Stephen M.

doi:10.3390/antibiotics7010008

Cited by 51 publications

(45 citation statements)

References 38 publications

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“…Others have previously observed that sensitive bacteria can survive phage attack in biofilms (26, 39), and proposed that this may be due to a high bacterial density or large molecules that reduce phage diffusion, such as exopolysac-charides (40, 41). A recent study showed that Escherichia coli produces an amyloid fiber network that protects cells in a biofilm individually and reduces phage diffusion (41).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study showed that Escherichia coli produces an amyloid fiber network that protects cells in a biofilm individually and reduces phage diffusion (41). Survival in the face of phage can instead occur because the bacteria reduce the expression of their phage receptors (42), or because they slow down growth as nutrients are depleted (40, 43, 44). Our data support a model whereby growth arrest can prevent phage infection (26, 32, 45–48).…”

Section: Discussionmentioning

confidence: 99%

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Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Testa

Berger

Piccardi

et al. 2019

Preprint

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Testa

Berger

Piccardi

et al. 2019

Preprint

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“…A typical method for introducing space in bacteria-phage modelling is by the use of cellular automata models 10,[28][29][30][31] . By utilizing a combination of lattices and diffusion of nutrient and phages, these models are used to study the interface between bacteria and phages in highly structured environments and have successfully addressed the importance of the spatial structures in various scenarios.…”

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confidence: 99%

Sustainability of spatially distributed bacteria-phage systems

Eriksen

Mitarai

Sneppen

2020

Sci Rep

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Virulent phages can expose their bacterial hosts to devastating epidemics, in principle leading to complete elimination of their hosts. Although experiments indeed confirm a large reduction of susceptible bacteria, there are no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modelling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how time delayed lysis, the spatial separation of initial bacterial positions, and the self-protection of bacteria growing in spherical colonies favour bacterial survival. our results suggest that spatial structures on the millimetre and submillimetre scale play an important role in maintaining microbial diversity. open Scientific RepoRtS | (2020) 10:3154 | https://doi.org/10.1038/s41598-020-59635-7www.nature.com/scientificreports www.nature.com/scientificreports/ been shown that a microcolony can grow exponentially in volume for a substantial period of time 8,9 , demonstrating the importance of exponential growth even in a spatially structured environment.With our model, we bridge the gap between the zero-dimensional mass action models and the spatial cellular automata models, and thereby incorporate both spatial structure and exponential growth of bacteria. This allows us to resolve length scales ranging from micrometres to more than centimetres while retaining (some of) the submillimetre behaviour of the cellular automata models. In particular, we are interested in systems where the bacteria form microcolonies, as is seen when bacteria grow in semisolid medium. We approximate the submillimetre structure of the colonies and retain exponential growth by making modifications to the traditional Lotka-Volterra models. It is worth noting that a similar approach of coupling mass-action growth and lattice model was taken in ref. 32 to simulate the phage attack on a biofilm with the spacial resolution of ~ 4 μm. We here consider length scales which are orders of magnitude larger where one lattice site can contain several of microcolonies. This allows for faster and larger-scale simulations while including the effects of colony structure in the phage-bacteria interaction as described below.We partition space into a three-dimensional lattice, which allows for spatial variation in the densities of phage and bacteria (see Fig. 1(a)). Each box in the lattice is well-mixed, meaning that bacterial colonies within each box are identical, i.e. they have the same size and composition as each other, but they are typically different from colonies in other boxes. Due to their small size, phages and nutrients diffuse readily around in the system, while the much larger bacteria remain fixed in space. Consequently, the phages and the nutrients need to propagate before interacting with distant areas, and we include diffusion to couple the dynamics in one box with its neighbouring boxes (see Fig. 1(b))....

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“…The continuous presence of a large population of susceptible host may act as a propagating host for the phage DC-56, granting its endurance [11, 65]. Nevertheless, we cannot tell whether this is a non-immune population, associated with the fitness cost of maintaining a fully active CRISPR-Cas system [66, 67] or that the population maintains active different defense mechanisms or it is protected from phage exposure by the spatial heterogeneity of the environment [68].…”

Section: Discussionmentioning

confidence: 99%

Long-run bacteria-phage coexistence dynamics under natural habitat conditions in an environmental biotechnology system

Guerrero

Pérez

Orellana

et al. 2020

Preprint

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Bacterial viruses are widespread and abundant across natural and engineered habitats. They influence ecosystem functioning through interactions with their hosts. Laboratory studies of phage-host pairs have advanced our understanding of phenotypic and genetic diversification in bacteria and phages. However, the dynamics of phage-host interactions has been seldom recorded in complex natural environments. We conducted an observational metagenomic study of the dynamics of interaction between Gordonia and their phages using a three-year data series of samples collected from a full-scale wastewater treatment plant. The aim was to obtain a comprehensive picture of the coevolution dynamics in naturally evolving populations at relatively high time resolution. Co-evolution was followed by monitoring changes over time in the CRISPR loci of Gordonia metagenome-assembled genome, and reciprocal changes in the viral genome. Genome-wide analysis indicated low strain variability of Gordonia, and almost clonal conservation of the trailer-end of the CRISPR loci. Incorporation of newer spacers gave rise to multiple coexisting bacterial populations. A host population containing a CRISPR array variant, which did not contain spacers against the coexisting phages, accounted for more than half of the total host abundance in the majority of samples. Phages genome co-evolved by introducing directional changes, with no preference for mutations within the protospacer and PAM regions. Metagenomic reconstruction of time-resolved variants of host and virus genomes revealed how selection operates at the population level. In activated sludge, it differed from the arms-race observed in nutrient rich media and resembled the fluctuating selection dynamics observed in natural environments.

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Phage-Bacterial Dynamics with Spatial Structure: Self Organization around Phage Sinks Can Promote Increased Cell Densities

Cited by 51 publications

References 38 publications

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Phage efficacy in infecting dual-strain biofilms ofPseudomonas aeruginosa

Sustainability of spatially distributed bacteria-phage systems

Long-run bacteria-phage coexistence dynamics under natural habitat conditions in an environmental biotechnology system

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