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Updated: May 28, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
A Trade-Off Between Antimicrobial Peptide Resistance and Sensitivity to Host Immune Effectors in Staphylococcus
Baydaa El Shazely1,2, Jens Rolff1,3
1Institut für Biologie, Evolutionary Biology Freie Universität Berlin Berlin Germany.
Abstract:
Antimicrobial peptides (AMPs) are essential immune effectors of multicellular organisms. Bacteria can evolve resistance to AMPs. Surprisingly, when used to challenge the yellow mealworm beetle, Tenebrio molitor, Staphylococcus aureus resistant to an abundant AMP (tenecin 1) of the very same host species did not increase host mortality or bacterial load compared to infections with wild-type S. aureus. A possible explanation is that antimicrobial resistance is costly due to the collaterally increased sensitivity of AMP-resistant strains to other immune effectors. Here, we study the sensitivity of a group of AMP-resistant S. aureus strains (resistant to tenecin 1 or a combination of tenecin 1 + 2) to other immune effectors such as phenoloxidase and other AMPs in vivo. Using RNAi-based knockdown, we investigate S. aureus survival in insect hosts lacking selected immune effectors. We find that all except one AMP-resistant strain displayed collateral sensitivity toward phenoloxidase. Some AMP-resistant strains show sensitivity to components of the yellow mealworm beetle AMP defense cocktail. Our findings are consistent with the idea that resistance to AMPs does not translate into changes in virulence because it is balanced by the collaterally increased sensitivity to other host immune effectors. AMP resistance fails to provide a net survival advantage to S. aureus in a host environment that is dominated by AMPs.
Insights
Antimicrobial resistance in bacteria is costly. Resistant bacteria showed increased sensitivity to other immune defenses, negating survival advantages in the yellow mealworm beetle.
Area of Science:
- * Insect immunity
- * Microbial pathogenesis
- * Evolutionary biology
Background:
- * Antimicrobial peptides (AMPs) are key immune molecules in multicellular organisms.
- * Bacteria can develop resistance to AMPs, potentially impacting virulence.
- * The yellow mealworm beetle (Tenebrio molitor) provides a model to study host-pathogen interactions.
Purpose of the Study:
- * To investigate the virulence and immune sensitivity of AMP-resistant Staphylococcus aureus strains in Tenebrio molitor.
- * To determine if resistance to one AMP (tenecin 1) confers collateral sensitivity to other immune effectors.
- * To explore the role of phenoloxidase and other AMPs in combating resistant bacterial strains.
Main Methods:
- * Infection of Tenebrio molitor beetles with wild-type and AMP-resistant Staphylococcus aureus strains.
- * Assessment of host mortality and bacterial load.
- * RNA interference (RNAi) to knock down specific immune effectors (phenoloxidase, AMPs) in beetles.
- * Testing AMP-resistant strains against phenoloxidase and beetle AMP cocktail.
Main Results:
- * AMP-resistant S. aureus strains did not exhibit increased virulence compared to wild-type strains in T. molitor.
- * Most AMP-resistant strains showed collateral sensitivity to phenoloxidase.
- * Some AMP-resistant strains were also sensitive to other components of the beetle's AMP defense.
- * Resistance to tenecin 1 did not confer a net survival advantage in the beetle host.
Conclusions:
- * Antimicrobial resistance in S. aureus is balanced by collateral sensitivity to other host immune mechanisms.
- * The cost of resistance, through increased susceptibility to other effectors, prevents enhanced virulence.
- * Host immune environments can select against AMP resistance by exploiting these trade-offs.
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