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Updated: Jun 13, 2025
Kinetic Visualization of Single-Cell Interspecies Bacterial Interactions
Published on: August 5, 2020
Interplay of virulence factors shapes ecology and treatment outcomes in polymicrobial infections
C Herzberg1, E N van Meegen1, J G C van Hasselt1
1Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
Abstract:
Polymicrobial infections, caused by a community of multiple micro-organisms, are often associated with increased infection severity and poorer patient outcomes. The design of improved antimicrobial treatment strategies for PMIs can be supported by an understanding of their ecological and evolutionary dynamics. Bacterial species present in polymicrobial infections can produce virulence factors to inhibit host immune responses, such as neutrophil recruitment and phagocytosis. The presence of virulence factors can indirectly affect other bacterial species acting as a type of host-mediated interspecies interaction. The aim of this study was to assess how bacterial virulence factors targeting neutrophil function influence ecology and treatment outcomes of PMIs. An agent-based model was constructed which describes a dual-species bacterial population in the presence of neutrophils and a bacteriostatic drug. Our analysis has revealed unforeseen dynamics of the interplay of multiple virulence factors acting as interspecies interaction. We found that the distribution of two phagocytosis-inhibiting virulence factors amongst species can impact whether they have a mutually protective effect for both species. The addition of a virulence factor inhibiting neutrophil recruitment was found to reduce the protective effect of phagocytosis-inhibiting virulence factors. Furthermore we demonstrate the importance of virulence strength of a species relative to other virulent species to determine the fate of a species. We conclude that virulence factors are an important driver of population dynamics in polymicrobial infections, and may be a relevant therapeutic target for treatment of polymicrobial infections.
Insights
Polymicrobial infections (PMIs) involve complex bacterial interactions. Targeting bacterial virulence factors, which influence immune responses, can improve treatment outcomes for these severe infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Computational Biology
Background:
- Polymicrobial infections (PMIs) are caused by multiple microorganisms and are linked to increased disease severity and worse patient outcomes.
- Understanding the ecological and evolutionary dynamics of PMIs is crucial for developing effective antimicrobial strategies.
- Bacterial virulence factors can modulate host immune responses, influencing interspecies interactions within PMIs.
Purpose of the Study:
- To investigate how bacterial virulence factors targeting neutrophil function impact the ecology and treatment outcomes of PMIs.
- To model the interplay between bacterial species, host immune cells (neutrophils), and antimicrobial drugs in a polymicrobial setting.
Main Methods:
- Construction of an agent-based model simulating a dual-species bacterial population interacting with neutrophils and a bacteriostatic drug.
- Analysis of the dynamics arising from the interaction of multiple virulence factors, including those inhibiting phagocytosis and neutrophil recruitment.
- Evaluation of the impact of virulence factor distribution and relative virulence strength on species survival and population dynamics.
Main Results:
- Virulence factors mediating interspecies interactions can lead to unforeseen ecological dynamics.
- The distribution of phagocytosis-inhibiting virulence factors influences whether bacterial species offer mutual protection.
- Inhibiting neutrophil recruitment can diminish the protective effects conferred by phagocytosis-inhibiting factors.
- The relative virulence strength of a species is critical in determining its persistence within the polymicrobial community.
Conclusions:
- Bacterial virulence factors are significant drivers of population dynamics in polymicrobial infections.
- Targeting virulence factors represents a potential therapeutic strategy for treating PMIs.
- Modulating host-mediated interspecies interactions through virulence factor manipulation may offer new treatment avenues.
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