Microcalorimetry: A Novel Application to Measure In Vitro Phage Susceptibility of Staphylococcus aureus in Human Serum

Molendijk, Michèle M.; Phan, My V. T.; Bode, L.; Strepis, Nikolas; Prasad, Divyae K.; Worp, Nathalie; Nieuwenhuijse, David F.; Schapendonk, Claudia M. E.; Boekema, B.K.H.L.; Verbon, Annelies; Graaf, Miranda de; Wamel, Willem J. B. van

doi:10.3390/v15010014

Cited by 4 publications

(2 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When bacteria interact with polymers, the wall teichoic acid receptor is masked or obscured thereby hindering bacteriophages from attaching to this binding receptor. In human plasma this has also been previously reported 23,24 . These findings are important for clinicians to be cognizant about because if a bacteriophage cannot bind to a surface receptor no lysis will occur.…”

Section: Discussionsupporting

confidence: 74%

Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Yu,

Doub,

Mao

et al. 2023

Journal Orthopaedic Research

View full text Add to dashboard Cite

Bacteriophage therapy is a promising adjuvant therapy for the treatment of periprosthetic joint infections. However, there is a paucity of knowledge about the activity of bacteriophages in synovial fluid. Therefore, this study evaluated the activity of a clinically used bacteriophage in synovial fluid as well as the ability of that bacteriophage to prevent the formation of and eradicate bacteria in synovial fluid induced aggregates. The results of this study reinforce that synovial fluid induced aggregates form rapidly in numerous synovial fluid concentrations. More importantly, there was a statistically significant reduction in bacteriophage activity in synovial fluid compared to tryptic soy broth (p< 0.05) and the bacteriophage could not prevent the formation synovial fluid induced aggregates. Also the bacteriophage could not significantly reduce the amount of bacteria in the synovial fluid induced aggregates when compared to controls, and this was not secondary to resistance. Rather the reduced activity seems to be caused by bacteriophages being hindered in the ability to attach to bacterial receptors. We hypothesize this occurred because the viscosity of synovial fluid slowed bacteriophage interactions with planktonic bacteria and the synovial fluid polymers obstructed the bacteriophage attachment receptors thereby preventing attachment to bacteria in the aggregates. These findings have clinical ramifications, supporting the use of bacteriophage therapy as an adjunct to surgical interventions and not in isolation, at the nascent stage. While these findings show a shortcoming of bacteriophage therapy in periprosthetic joint infections, the knowledge gained should spearhead further research to ultimately devise effective and reproducible bacteriophage therapeutics.This article is protected by copyright. All rights reserved.

show abstract

Section: Discussionsupporting

confidence: 74%

Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Yu,

Doub,

Mao

et al. 2023

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…Additionally, direct binding of C1q to viruses such as dengue, influenza A, and SARS-CoV-2 seems to be sufficient in some cases to reduce infectivity [52][53][54]. Inactivation of phages by complement components independent of antibodies could explain the observations reported in several studies where phage activity was compromised in the presence of human serum or plasma [55][56][57].…”

Section: Discussionmentioning

confidence: 98%

Human Complement Inhibits Myophages against Pseudomonas aeruginosa

Egido,

Dekker,

Toner-Bartelds

et al. 2023

Viruses

View full text Add to dashboard Cite

Therapeutic bacteriophages (phages) are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this research, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in the presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we showed that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in the presence of active complement. Our results indicate that interactions with complement may affect the in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

show abstract

Bacteriophage therapy reduces Staphylococcus aureus in a porcine and human ex vivo burn wound infection model

Molendijk,

Boekema,

Lattwein

et al. 2024

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Burn wounds are a major burden, with high mortality rates due to infections. Staphylococcus aureus is a major causative agent of burn wound infections, which can be difficult to treat because of antibiotic resistance and biofilm formation. An alternative to antibiotics is the use of bacteriophages, viruses that infect and kill bacteria. We investigated the efficacy of bacteriophage therapy for burn wound infections, in both a porcine and a newly developed human ex vivo skin model. In both models, the efficacy of a reference antibiotic treatment (fusidic acid) and bacteriophage treatment was determined for a single treatment, successive treatment, and prophylaxis. Both models showed a reduction in bacterial load after a single bacteriophage treatment. Increasing the frequency of bacteriophage treatments increased bacteriophage efficacy in the human ex vivo skin model, but not in the porcine model. In both models, prophylaxis with bacteriophages increased treatment efficacy. In all cases, bacteriophage treatment outperformed fusidic acid treatment. Both models allowed investigation of bacteriophage-bacteria dynamics in burn wounds. Overall, bacteriophage treatment outperformed antibiotic control underlining the potential of bacteriophage therapy for the treatment of burn wound infections, especially when used prophylactically.

show abstract

Microcalorimetry: A Novel Application to Measure In Vitro Phage Susceptibility of Staphylococcus aureus in Human Serum

Cited by 4 publications

References 75 publications

Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Human Complement Inhibits Myophages against Pseudomonas aeruginosa

Bacteriophage therapy reduces Staphylococcus aureus in a porcine and human ex vivo burn wound infection model

Contact Info

Product

Resources

About