Abstract
Patients with cystic fibrosis (CF) have numerous episodes of lung infections during their lifetime leading to a decline in lung function. Among the opportunistic pathogenic bacteria involved in these infections, Staphylococcus aureus (Sa) and Pseudomonas aeruginosa (Pa) are the most frequently identified and studied. However, other bacteria, currently described as emerging, such as Stenotrophomonas maltophilia (Sm), bacteria of the genus Achromobacter (Ax) and nontuberculous mycobacteria (Ma) or less common such as the genus Bordetella (Bo), may be involved in these infectious episodes. These bacteria have an environmental origin, as it is the case for Pa, the major pathogen in this context. However, the environmental sources of contamination to which CF patients are exposed remain largely unknown. Similarly, the versatility of the emerging or more rarely identified pathogens, as well as the interactions that they are able to establish within a microbial community and the adaptive processes that allow them to establish and persist in the respiratory tract of patients, have been less studied until now.In this context, we first mapped the environmental reservoirs of these bacteria in the homes of CF patients and demonstrated the presence of numerous of these bacteria in some (Pa, Bo) or all homes (Ma, Sm and Ax), particularly in moist areas. Comparison of clinical and environmental strains allowed the identification of potential situations of transmission from the environment to patients (Pa, Sm, A. mucicolens and M. chelonae). A panel of clinical and environmental strains (Ax, Sm, Bo) was then characterized for certain previously unknown traits (clinical impact and antibiotic resistance for Bo; capacity for bacterial interactions for Ax and Sm). A monocentric clinico-microbiological study of Bo isolations carried out over 7 years showed that the patients all presented an exacerbation at the time of Bo isolation and led to the first description of Bordetella genogroup 2 and its characteristics during CF (capacity for chronic colonization of the respiratory tract and multiresistance to antibiotics). The study of the competitive abilities of a large panel of clinical CF strains and those of Ax had never been done before. We showed that the effects of bacterial competition between opportunistic CF pathogens are frequent (33% of the 203 co-cultures performed between Pa, Sm, Ax and Sa) and multiple, affecting the growth, motility and/or overall pigment production and virulence of Pa. In our study, these interaction effects were significantly more frequent when at least one clinical strain was tested in the co-cultures compared to environmental strains. In addition, the competitive ability of some Ax strains against Pa strains of clinical and environmental origin was demonstrated and further explored with regard to its consequences on Pa virulence. Decreased virulence of Pa has been observed in the Zebrafish embryo model and correlated with the reduced siderophore and pyocyanin production by Pa in the presence of Ax. The mechanisms underlying these observations remain to be elucidated and proteomic investigations are in progress.The study of the link between the bacterial strains isolated from the environment and the respiratory tract of CF patients must be pursued, taking into account both the specificities and the complexity of these ecosystems (selective pressures, polymicrobial communities) but also the versatility of emerging pathogens and their various competitive and adaptive capacities in the pulmonary environment. In a more detailed way, the mapping of the sources of exposure of CF patients in their homes justifies the establishment of specific hygiene recommendations, targeted on the areas most frequently hosting the bacteria described as emerging during this pathology.