Rapid Aggregation of Staphylococcus aureus in Synovial Fluid Is Influenced by Synovial Fluid Concentration, Viscosity, and Fluid Dynamics, with Evidence of Polymer Bridging

Staats, Amelia; Burback, Peter W; Schwieters, Andrew; Li, Daniel D.; Sullivan, Anne C.; Horswill, Alexander R.; Stoodley, Paul

doi:10.1128/mbio.00236-22

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…SSF induces aggregation in both S. aureus and S. epidermidis 40,42 . Aggregation of bacterial cells also promotes antimicrobial resistance during infection, which can complicate treatment of PJIs 44 .…”

Section: Resultsmentioning

confidence: 99%

Genotypic and phenotypic characterization ofEnterococcus faecalisisolates from periprosthetic joint infections

Haeberle,

Greenwood-Quaintance,

Zar

et al. 2024

Preprint

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Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacteriumEnterococcus faecalis, which can be highly antibiotic resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2-11% of PJIs.E. faecalisPJIs are understudied compared to those caused by other pathogens, such asStaphylococcus aureus. This motivates the need to generate a comprehensive understanding ofE. faecalisPJIs to guide future treatments for these infections. To address this, we describe a panel ofE. faecalisstrains isolated from the surface of prosthetic joints in a cohort of individuals treated at Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage ofE. faecalisPJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences inin vitrobiofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Lastly, we evaluated antibiotic efficacy of these isolates and found strain specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity amongE. faecalisPJI isolates which will provide valuable insight and resources for futureE. faecalisPJI research.ImportancePeriprosthetic joint infections (PJIs) affect ∼1-2% of those who undergo joint replacement surgery.Enterococcus faecalisis a Gram-positive opportunistic pathogen that causes ∼10% of PJIs in the United States each year, but our understanding of how and whyE. faecaliscauses PJIs is limited.E. faecalisinfections are typically biofilm associated and can be difficult to clear with antibiotic therapy. Here, we provide complete genomes for fourE. faecalisPJI isolates from the Mayo Clinic. These isolates have strain-specific differences in biofilm formation, aggregation, and antibiotic susceptibility in simulated synovial fluid. These results provide important insight into genomic and phenotypic features ofE. faecalisisolates from PJI.

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Section: Resultsmentioning

confidence: 99%

Genotypic and phenotypic characterization ofEnterococcus faecalisisolates from periprosthetic joint infections

Haeberle,

Greenwood-Quaintance,

Zar

et al. 2024

Preprint

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“…This is likely a consequence of the lack of traditional motility of S . aureus and the viscosity of the SF itself inhibiting interactions between bacteria and the polymers in the SF 15,18,19 . However, under dynamic conditions aggregation occurred rapidly (within 20 min) and SEM images of the aggregates (Figure 1C) reinforce dense collections of bacteria nested with SF polymers.…”

Section: Discussionmentioning

confidence: 95%

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

Yu,

Doub,

Mao

et al. 2023

Journal Orthopaedic Research

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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.

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“…50 Synovial fluid bacterial aggregates have also been proven to form secondary to interactions with polymers, making them recalcitrant to antibiotic therapy. 51 However, there is a paucity of research evaluating the ramifications of bacteriophage activity when bacteria interact with in vivo macromolecules. These interactions may mask the bacteriophage attachment receptors thereby not allowing for bacteriophage attachment (Figure 4).…”

Section: Bacterial Interactions With In Vivo Environments and Effects...mentioning

confidence: 99%

“…For instance, S. aureus uses clumping factor to cleave fibrinogen to fibrin forming a fibrin coat around the bacteria (Figure 4). 50 Synovial fluid bacterial aggregates have also been proven to form secondary to interactions with polymers, making them recalcitrant to antibiotic therapy 51 . However, there is a paucity of research evaluating the ramifications of bacteriophage activity when bacteria interact with in vivo macromolecules.…”

Section: Additional Translational Research Needed To Advance Bacterio...mentioning

confidence: 99%

Bacteriophage therapy for periprosthetic joint infections: Current limitations and research needed to advance this therapeutic

Doub

Urish

2022

Journal Orthopaedic Research

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Bacteriophage therapy is a promising treatment for periprosthetic joint infections (PJIs), particularly given these agents have innate abilities to degrade the biofilm matrix and lyse bacteria within. However, many aspects of this therapy are poorly understood causing treatments to lack uniform effectiveness and reproducibility, which is in part a consequence of several inherent limitations to using bacteriophages to treat PJI. Herein, these limitations are discussed as are additional translational research that needs to be conducted to advance this therapeutic. These include determining if bacteria causing PJIs are polyclonal, consequences of bacteriophage attachment receptor phenotypic variations and ramifications of bacteriophage activity when bacteria interact with in vivo macromolecules. Only with the realization of the current limitations and subsequent knowledge gained from translational research will the potential of bacteriophages to reduce the morbidity and mortality in PJI be fully elucidated.

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Rapid Aggregation of Staphylococcus aureus in Synovial Fluid Is Influenced by Synovial Fluid Concentration, Viscosity, and Fluid Dynamics, with Evidence of Polymer Bridging

Abstract: Infection is a major complication of knee and hip joint replacement surgery, which is used to treat arthritis or joint damage. We have shown that Staphylococcus aureus , a common bacterial pathogen, aggregates upon contact with synovial fluid.

Cited by 14 publications

References 35 publications

Genotypic and phenotypic characterization ofEnterococcus faecalisisolates from periprosthetic joint infections

Genotypic and phenotypic characterization ofEnterococcus faecalisisolates from periprosthetic joint infections

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

Bacteriophage therapy for periprosthetic joint infections: Current limitations and research needed to advance this therapeutic

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