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Methods to Inhibit Bacterial Pyomelanin Production and Determine the Corresponding Increase in Sensitivity to Oxidative Stress
Published on: August 31, 2015
A bacterial pigment provides cross-species protection from H2O2- and neutrophil-mediated killing
Yiwei Liu1,2, Eleanor A McQuillen3, Pranav S J B Rana1,2
1Department of Microbiology, Ohio State University, Columbus, OH 43210.
Abstract:
Bacterial infections are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus cause chronic co-infections, which are more problematic than mono-species infections. Understanding the mechanisms of their interactions is crucial for treating co-infections. Staphyloxanthin (STX), a yellow pigment synthesized by the S. aureus crt operon, promotes S. aureus resistance to oxidative stress and neutrophil-mediated killing. We found that STX production by S. aureus, either as surface-grown macrocolonies or planktonic cultures, was elevated when exposed to the P. aeruginosa exoproduct, 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). This was observed with both mucoid and non-mucoid P. aeruginosa strains. The induction phenotype was found in a majority of P. aeruginosa and S. aureus clinical isolates examined. When subjected to hydrogen peroxide or human neutrophils, P. aeruginosa survival was significantly higher when mixed with wild-type (WT) S. aureus, compared to P. aeruginosa alone or with an S. aureus crt mutant deficient in STX production. In a murine wound model, co-infection with WT S. aureus, but not the STX-deficient mutant, enhanced P. aeruginosa burden and disease compared to mono-infection. In conclusion, we identified a role for P. aeruginosa HQNO mediating polymicrobial interactions with S. aureus by inducing STX production, which consequently promotes resistance to the innate immune effectors H2O2 and neutrophils. These results further our understanding of how different bacterial species cooperatively cause co-infections.
Insights
Pseudomonas aeruginosa exoproduct HQNO boosts Staphylococcus aureus staphyloxanthin production. This enhances bacterial survival against oxidative stress and neutrophils, worsening co-infections.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Polymicrobial bacterial infections, particularly chronic co-infections by Pseudomonas aeruginosa and Staphylococcus aureus, pose significant clinical challenges.
- Staphylococcus aureus produces staphyloxanthin (STX), a pigment conferring resistance to oxidative stress and neutrophil killing.
- Understanding interspecies interactions is vital for developing effective treatments for polymicrobial infections.
Purpose of the Study:
- To investigate the interaction between Pseudomonas aeruginosa and Staphylococcus aureus in polymicrobial infections.
- To determine the role of Pseudomonas aeruginosa exoproducts in modulating Staphylococcus aureus virulence factors.
- To elucidate the mechanisms by which Staphylococcus aureus staphyloxanthin influences Pseudomonas aeruginosa survival during co-infection.
Main Methods:
- Exposure of Staphylococcus aureus cultures (macrocolonies and planktonic) to Pseudomonas aeruginosa exoproduct 2-heptyl-4-hydroxyquinoline N-oxide (HQNO).
- Assessment of staphyloxanthin production in Staphylococcus aureus.
- Evaluation of Pseudomonas aeruginosa survival in the presence of hydrogen peroxide and human neutrophils, with and without Staphylococcus aureus (wild-type and STX-deficient mutant).
- Murine wound co-infection model using wild-type and STX-deficient Staphylococcus aureus with Pseudomonas aeruginosa.
Main Results:
- Pseudomonas aeruginosa HQNO significantly induced staphyloxanthin production in Staphylococcus aureus.
- Pseudomonas aeruginosa survival against hydrogen peroxide and neutrophils was enhanced in co-cultures with wild-type Staphylococcus aureus compared to monocultures or cultures with STX-deficient mutants.
- Co-infection with wild-type Staphylococcus aureus, but not the STX-deficient mutant, increased Pseudomonas aeruginosa burden and disease severity in a murine wound model.
Conclusions:
- Pseudomonas aeruginosa HQNO mediates polymicrobial interactions by inducing Staphylococcus aureus staphyloxanthin production.
- Induced staphyloxanthin enhances Staphylococcus aureus resistance to innate immune effectors, indirectly promoting Pseudomonas aeruginosa survival.
- This study reveals a mechanism of cooperative virulence in polymicrobial infections, highlighting the role of bacterial exoproducts in modulating host-pathogen and pathogen-pathogen interactions.
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