Antagonistic and cooperative interactions between Pseudomonas aeruginosa and Staphylococcus aureus
2023
Online
Hochschulschrift
With increasing awareness of the distinct disease outcomes of polymicrobial infections, there is an urgent need for studies in this field. Pseudomonas aeruginosa and Staphylococcus aureus are considered model organisms to study polymicrobial interaction. They are two common pathogens causing chronic infections in the lungs of people with cystic fibrosis (CF) and wounds, suggesting their co-existence in vivo. They form biofilms that are tolerant to host clearance and antibiotic treatments. However, P. aeruginosa utilizes various mechanisms to antagonize S. aureus when grown together in vitro. We contribute to the studies of antagonistic mechanisms by proposing a novel role for P. aeruginosa Psl in killing S. aureus. Psl is an exopolysaccharide that exists in both cell-associated and cell-free forms and is important for biofilm formation. We found that a P. aeruginosa psl mutant had reduced antagonism towards S. aureus when grown in planktonic co-culture. Cell-free Psl was critical for the killing, as purified cell-free Psl was sufficient to kill S. aureus. Transmission electron microscopy of S. aureus treated with Psl revealed disrupted cell envelopes. We later found that Psl could induce S. aureus autolysis. Cell-free Psl also promoted S. aureus killing during growth in in vivo-like conditions. A positive correlation was identified between cell-free Psl production in P. aeruginosa CF clinical isolates and their ability to kill S. aureus. This could be a result of P. aeruginosa co-evolving with S. aureus in CF lungs. In conclusion, this part of the dissertation defines a novel role for P. aeruginosa Psl in killing S. aureus, potentially impacting the co-existence of these two opportunistic pathogens in vivo. P. aeruginosa and S. aureus cause chronic co-infections, which are more problematic than mono-species infections. This can be attributed to cooperative behaviors between the two pathogens in vivo. 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) is the most extensively studied P. aeruginosa factor involved in antagonizing S. aureus growth. It is known to inhibit S. aureus respiration. Staphyloxanthin (STX) is a yellow pigment synthesized by the S. aureus crt operon. It can promote S. aureus resistance to oxidative stress and neutrophil-mediated killing. We found that STX production in S. aureus, either as surface-grown macrocolonies or planktonic cultures, was elevated when exposed to sub-lethal concentrations of HQNO. This was observed with both mucoid and non-mucoid P. aeruginosa strains. The induction phenotype was found in the majority of the 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 S. aureus, in comparison to P. aeruginosa cultured alone or with an S. aureus crt mutant deficient in STX production. In a murine wound infection model, STX also conferred protection to P. aeruginosa against host innate immunity and promoted the establishment of infection. In this part of the dissertation, we identified a new cooperative behavior between the two pathogens, resulting in resistance to host ROS and increased bacterial burden during co-infections in vivo.Collectively, our work uncovers novel mechanisms involved in both antagonistic and cooperative behaviors between P. aeruginosa and S. aureus. Our findings contribute to the understanding of complex interactions between mixed species and provide valuable insights into future studies in polymicrobial infections.
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Antagonistic and cooperative interactions between Pseudomonas aeruginosa and Staphylococcus aureus
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Autor/in / Beteiligte Person: | Liu, Yiwei |
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Veröffentlichung: | 2023 |
Medientyp: | Hochschulschrift |
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