Bacteriophage Infection Dynamics: Multiple Host Binding Sites

Smith, Hal L.; Trevino, R. T.

doi:10.1051/mmnp/20094604

Cited by 21 publications

(13 citation statements)

References 30 publications

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“…The alternative approach for modelling cell lysis and phage replication uses delay differential equations (referred here as Model II). This approach is used somewhat more frequently in the literature 22 , 25 , 31 – 33 . The equations of Model II read as follows where τ is the time between infection and lysis.…”

Section: Methodsmentioning

confidence: 99%

“…Using of each of Models I and II has its advantages and disadvantages for modelling bacteria-phage interaction, thus in this study we will explore both of them. Note also that there exist more complicated bacteria-phage interaction models, for instance explicitly describing the number of phages currently bound to the bacterial cell (susceptible and/or infected) at the current moment of time or some models considering a non-fixed lysis time 25 , 33 . However, here we intentionally prefer to keep our parsimonious models of temperature dependent lysogeny as simple as possible to be able to understand the generic behaviour of such systems including the dependence of the dynamics on key parameters.…”

Section: Methodsmentioning

confidence: 99%

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Temperature-dependent virus lifecycle choices may reveal and predict facets of the biology of opportunistic pathogenic bacteria

Egilmez

Морозов

Clokie

et al. 2018

Sci Rep

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Melioidosis, a serious illness caused by Burkholderia pseudomallei, results in up to 40% fatality in infected patients. The pathogen is found in tropical water and soil. Recent findings demonstrated that bacterial numbers can be regulated by a novel clade of phages that are abundant in soil and water. These phages differentially infect their bacterial hosts causing lysis at high temperatures and lysogeny at lower temperatures. Thus seasonal and daily temperature variations would cause switches in phage-bacteria interactions. We developed mathematical models using realistic parameters to explore the impact of phages on B. pseudomallei populations in the surface water of rice fields over time and under seasonally changing environmental conditions. Historical records were used to provide UV radiation levels and temperature for two Thailand provinces. The models predict seasonal variation of phage-free bacterial numbers correlates with the higher risk of melioidosis acquisition during the “warm and wet” season. We find that enrichment of the environment may lead to irregular large amplitude pulses of bacterial numbers that could significantly increase the probability of disease acquisition. Our results suggest that the phages may regulate B. pseudomallei populations throughout the seasons, and these data can potentially help improve the melioidosis prevention efforts in Southeast Asia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Temperature-dependent virus lifecycle choices may reveal and predict facets of the biology of opportunistic pathogenic bacteria

Egilmez

Морозов

Clokie

et al. 2018

Sci Rep

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“…Recognising the shortcomings of phage therapy due to their special PK properties mentioned above, it can be assumed that the explanation for phage therapy being occasionally successful is phages' ability to replicate and compensate for a low dose. Different mathematical models and experiments with phages-bacteria, in batch or continuous cultures, have contributed to the understanding of their kinetics during in vitro infection (21)(22)(23)45,(50)(51)(52)(53). With basic mathematical models, it is easy to show that any virulent phage with ordinary infection characteristics will completely eliminate all bacteria if the titres of phages and bacteria are sufficiently high and if the bacteria are not allowed to become resistant (50).…”

Section: Phage Pharmacodynamicsmentioning

confidence: 99%

Pharmacological limitations of phage therapy

Nilsson

2019

Upsala Journal of Medical Sciences

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Clinical trial results of phage treatment of bacterial infections show a low to moderate efficacy, and the variation in infection clearance between subjects within studies is often large. Phage therapy is complicated and introduces many additional components of variance as compared to antibiotic treatment. A large part of the variation is due to in vivo pharmacokinetics and pharmacodynamics being virtually unknown, but also to a lack of standardisation. This is a consequence of the great variation of phages, bacteria, and infections, which results in different experiments or trials being impossible to compare, and difficulties in estimating important parameter values in a quantitative and reproducible way. The limitations of phage therapy will have to be recognised and future research focussed on optimising infection clearance rates by e.g. selecting phages, bacteria, and target bacterial infections where the prospects of high efficacy can be anticipated, and by combining information from new mathematical modelling of in vivo pharmacokinetic and pharmacodynamic processes and quantitatively assessed experiments.

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“…Previous studies on coexistence of phages and bacteria mostly focused on well-mixed, nearly homeostatic systems, such as cultures grown in chemostats [17][18][19][20][21][22][23]. Naturally occurring systems of phages and bacteria, however, often do not satisfy the conditions found under these defined laboratory settings.…”

Section: Introductionmentioning

confidence: 99%

Formation of phage lysis patterns and implications on co-propagation of phages and motile host bacteria

Gonzalez

Esteves

et al. 2020

PLoS Comput Biol

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Coexistence of bacteriophages, or phages, and their host bacteria plays an important role in maintaining the microbial communities. In natural environments with limited nutrients, motile bacteria can actively migrate towards locations of richer resources. Although phages are not motile themselves, they can infect motile bacterial hosts and spread in space via the hosts. Therefore, in a migrating microbial community coexistence of bacteria and phages implies their co-propagation in space. Here, we combine an experimental approach and mathematical modeling to explore how phages and their motile host bacteria coexist and co-propagate. When lytic phages encountered motile host bacteria in our experimental set up, a sectorshaped lysis zone formed. Our mathematical model indicates that local nutrient depletion and the resulting inhibition of proliferation and motility of bacteria and phages are the key to formation of the observed lysis pattern. The model further reveals the straight radial boundaries in the lysis pattern as a telltale sign for coexistence and co-propagation of bacteria and phages. Emergence of such a pattern, albeit insensitive to extrinsic factors, requires a balance between intrinsic biological properties of phages and bacteria, which likely results from coevolution of phages and bacteria. Author summaryCoexistence of phages and their bacterial hosts is important for maintaining the microbial communities. In a migrating microbial community, coexistence between phages and host bacteria implies that they co-propagate in space. Here we report a novel phage lysis pattern that is indicative of this co-propagation. The corresponding mathematical model we developed highlights a crucial dependence of the lysis pattern and implied phage-bacteria co-propagation on intrinsic properties allowing proliferation and spatial spreading of the microbes. In contrast, extrinsic factors, such as overall nutrient level, do not influence phage-bacteria coexistence and co-propagation. Findings from this work have strong PLOS COMPUTATIONAL BIOLOGY PLOS Computational Biology | https://doi.

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Bacteriophage Infection Dynamics: Multiple Host Binding Sites

Cited by 21 publications

References 30 publications

Temperature-dependent virus lifecycle choices may reveal and predict facets of the biology of opportunistic pathogenic bacteria

Temperature-dependent virus lifecycle choices may reveal and predict facets of the biology of opportunistic pathogenic bacteria

Pharmacological limitations of phage therapy

Formation of phage lysis patterns and implications on co-propagation of phages and motile host bacteria

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