mpact of co-infection and bacterial interactions between S. aureus and P. aeruginosa in a context of chronic lung infection

Led by Karen Moreau (PU) and Anne Doleans Jordheim (MCU-PH) with contribution of F. Vandenesch (PU-PH), and assistance of F. Couzon and S. Bastien (engineers)

The clinical consequences of polymicrobial infections became a major point of interest and have revealed a range of clinically important microbial interactions that may promote microbial growth and survival, enhance antimicrobial tolerance and/or alter virulence factor production. Understanding the mechanisms of these interactions and their clinical relevance is essential to rationally guide current therapies and to develop improved treatments.

We explore this question in the context of chronic bacterial respiratory infections in patients with Cystic Fibrosis (CF). S. aureus and P. aeruginosa co-infect 30 to 50% of patients. However, knowledge and impact of co-infection with these species is limited.

In previous studies, we have described two types of bacterial interactions: (i) the well-known competitive state in which P. aeruginosa inhibits the growth of S. aureus and (ii) the coexistence state where the two bacteria can grow together. We have shown that the coexistence relationship is predominant in Cystic Fibrosis patients. Furthermore, we have demonstrated that coexistence induces large modifications of the transcriptome and phenotypic traits of the two species to allow bacterial cooperation contributing to persistence.

This project continues along three axes:

1. On the clinical side: what is the impact of co-infection and co-existence of S. aureus and P. aeruginosa on the patient outcome. We plan to collect clinical data from patients to assess the impact of bacterial co-infection and co-existence on the clinical history of patients;
2. On evolutionary aspects: the switch from competitive to coexistence interaction with S. aureus is linked to the evolution of P. aeruginosa during chronic infection. In order to understand and identify the molecular mechanisms of this evolution, in vitro experimental evolution as well as longitudinal study of chronic infection strains in patients are performed using comparative genomic and proteomic approaches. We aim to understand the importance of S. aureus in this evolutive process and identifying the genomic modifications involved in the change of interaction between the two species.
3. On host-pathogen relationship: As the diseased CF airway lumen is characterized by excessive, sustained and ineffective neutrophil-dominated inflammatory response, we want to explore how bacterial coinfection and coexistence may affect the host cell response. For this purpose, we developed relevant model of human pulmonary epithelium.

Cooperative behaviors between S. aureus and P. aeruginosa. From Camus et al., 2021

Recent publications:

Camus L, Briaud P, Vandenesch F, Moreau K. How bacterial adaptation to Cystic Fibrosis environment shapes interactions between Pseudomonas aeruginosa and Staphylococcus aureus. Front Microbiol. 2021 Mar 3;12:617784. doi: 10.3389/fmicb.2021.617784. eCollection 2021.

Camus L, Vandenesch F, Moreau K. From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the Cystic Fibrosis environment. Microb Genom. 2021 Feb 2. doi: 10.1099/mgen.0.000513.

Camus L, Briaud P, Bastien S, Elsen S, Doléans-Jordheim A, Vandenesch F, Moreau K. Trophic cooperation promotes bacterial survival of Staphylococcus aureus and Pseudomonas aeruginosa. ISME J. 2020 Dec;14(12):3093-3105. doi: 10.1038/s41396-020-00741-9.

Briaud P, Bastien S, Camus L, Boyadjian M, Reix P, Mainguy C, Vandenesch F, Doléans-Jordheim A, Moreau K. Impact of Coexistence Phenotype Between Staphylococcus aureus and Pseudomonas aeruginosa Isolates on Clinical Outcomes Among Cystic Fibrosis Patients. Front Cell Infect Microbiol. 2020 Jun 3; 10:266. doi: 10.3389/fcimb.2020.00266.

Briaud P, Camus L, Bastien S, Doléans-Jordheim A, Vandenesch F, Moreau K. Coexistence with Pseudomonas aeruginosa alters Staphylococcus aureus transcriptome, antibiotic resistance and internalization into epithelial cells. Sci Rep. 2019 Nov 12;9(1):16564. doi: 10.1038/s41598-019-52975-z.

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