The Virulence Index: A Metric for Quantitative Analysis of Phage Virulence

Storms, Zachary J.; Teel, Matthew R.; Mercurio, Kevin; Sauvageau, Dominic

doi:10.1101/606350

Cited by 10 publications

(22 citation statements)

References 51 publications

(1 reference statement)

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“…The effects of nutritional environment were briefly investigated by Storms et al. in the development of the virulence index, a method of quantifying phage virulence relative to the natural host growth rate [ 39 ]. In the study of [ 39 ] it was also shown that temperature had an effect on phage virulence alongside growth media, as well as the same phage having different dynamics in secondary host strains.…”

Section: Discussionmentioning

confidence: 99%

“…in the development of the virulence index, a method of quantifying phage virulence relative to the natural host growth rate [ 39 ]. In the study of [ 39 ] it was also shown that temperature had an effect on phage virulence alongside growth media, as well as the same phage having different dynamics in secondary host strains. These are all factors that need to be taken into consideration when optimising phage cocktails for use outside of the lab.…”

Section: Discussionmentioning

confidence: 99%

“…The area under the curve (AUC) was calculated using MatLab, following the methodology of [ 39 ]. The AUC method allowed direct comparison of the phages in each host and media in a high-throughput and reproducible manner.…”

Section: Methodsmentioning

confidence: 99%

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CAUTI’s next top model – Model dependent Klebsiella biofilm inhibition by bacteriophages and antimicrobials

Townsend¹,

Moat²,

Jameson³

2020

Biofilm

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Klebsiella infections, including catheter associated urinary tract infections, are a considerable burden on health care systems. This is due to their difficulty to treat, caused by antimicrobial resistance and their ability to form biofilms. In this study, we investigated the use of a Klebsiella phage cocktail to reduce biofilm viability. We used two methodologies to investigate this, a standard 96-well plate assay and a more complicated Foley catheter-based model. The phage cocktail was used alone and in combination with clinically relevant antibiotic treatments. Viability was measured by both a resazurin based stain and colony forming unit counts, of cells sloughed off from the biofilm. We showed that phage infection dynamics and host survival vary significantly in different standard laboratory media, presumably due to the expression of different surface receptors and capsule composition by the bacteria effecting phage binding. This underscores the importance of a realistic model for developing phage therapy. We demonstrate that bacteriophage-based treatments are a viable option for preventing Klebsiella colonisation and biofilm formation on urinary catheters. Phage cocktails were able to significantly reduce the amount of biofilm that formed when they were present during early biofilm formation. The phages used in this study were unable to significantly reduce a pre-formed mature biofilm, despite encoding depolymerases. Phages applied together with antimicrobial treatments, showed synergistic interactions, in some cases the combined treatment was much more effective than antimicrobial treatments alone. We show that phage cocktails have the potential to prevent Klebsiella biofilms in catheters, if used early or as a preventative treatment and will work well alongside standard antibiotics in the treatment of catheter-associated urinary tract infections (CAUTI).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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CAUTI’s next top model – Model dependent Klebsiella biofilm inhibition by bacteriophages and antimicrobials

Townsend¹,

Moat²,

Jameson³

2020

Biofilm

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“…The two virulence metrics the virulence Index (VP) and MV50 were calculated based on the protocol described by Storms and others 47 . Briefly, bacterial cultures were grown to exponential phase and then adjusted (as described for lysis period) to an optical density equivalent to 1 x 10 8 cfu/mL.…”

Section: Methodsmentioning

confidence: 99%

Isolation and characterisation ofKlebsiellaphages for phage therapy

Townsend

Kelly

Gannon

et al. 2020

Preprint

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Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections, in both community and nosocomial settings, particularly pneumonia, urinary tract infection and septicaemia. We report the successful isolation and characterisation of 30 diverse Klebsiella-infecting phages. The isolated phages are diverse, spanning six different phage families and nine genera. These phages comprise of both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected 11 of 18 different Klebsiella capsule types across all six Klebsiella species tested. Our Klebsiella-infecting lytic phages are suitable for phage therapy, based on the criteria that they encode no known toxin or antimicrobial resistance genes. However, none of the characterised phages were able to suppress the growth of Klebsiella for more than 7 hours. This indicates that for successful phage therapy, a mixed cocktail of multiple phages is necessary to treat Klebsiella infections.

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“…In comparing host growth using AUC as a metric for relative virulence, two sets of limits were also used. Given the demonstrated inadequacy of µ max in determining V R in non-lytic viral infections, an alternative approach is to calculate a percent inhibition (PI AUC ) of host growth [15][16][17][18] based on AUC for infected (AUC infected ) and uninfected controls (AUC CTL ).…”

Section: Accessmentioning

confidence: 99%

Quantifying relative virulence: when μ max fails and AUC alone just is not enough

Ceballos

Stacy

2021

Journal of General Virology

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A challenge in virology is quantifying relative virulence (V R) between two (or more) viruses that exhibit different replication dynamics in a given susceptible host. Host growth curve analysis is often used to mathematically characterize virus–host interactions and to quantify the magnitude of detriment to host due to viral infection. Quantifying V R using canonical parameters, like maximum specific growth rate (μ max), can fail to provide reliable information regarding virulence. Although area-under-the-curve (AUC) calculations are more robust, they are sensitive to limit selection. Using empirical data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that has proven to be more robust than existing methods for assessing V R. This metric (I SC) accurately aligns biological phenomena with quantified metrics to determine V R. It also addresses a gap in virology by permitting comparisons between different non-lytic virus infections or non-lytic versus lytic virus infections on a given host in single-virus/single-host infections.

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The Virulence Index: A Metric for Quantitative Analysis of Phage Virulence

Cited by 10 publications

References 51 publications

CAUTI’s next top model – Model dependent Klebsiella biofilm inhibition by bacteriophages and antimicrobials

CAUTI’s next top model – Model dependent Klebsiella biofilm inhibition by bacteriophages and antimicrobials

Isolation and characterisation ofKlebsiellaphages for phage therapy

Quantifying relative virulence: when μ max fails and AUC alone just is not enough

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