In vitro Interactions of Pseudomonas aeruginosa With Scedosporium Species Frequently Associated With Cystic Fibrosis

Abstract

Members of the Scedosporium apiospermum species complex are the second most frequently isolated pathogens after Aspergillus fumigatus from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of A. fumigatus in vitro. Considering all the above discussed points, we aimed to test how Pseudomonas aeruginosa influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on Scedosporium species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by P. aeruginosa. To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of Scedosporium conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, P. aeruginosa either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several Scedosporium isolates. These data raise the possibility that a P. aeruginosa infection or a previously administered antibacterial therapy might be able to increase the chance of a Scedosporium colonization in a CF lung.

Deciphering the Ecology of Cystic Fibrosis Bacterial Communities: Towards Systems-Level Integration

“…Such findings underscore the importance of systems-level approaches that more fully reflect the complexity of these microbiota. Additionally, agonistic and antagonistic interactions among members of the CF airway microbiota can occur, influencing community composition dynamics, as suggested by various reports and confirmed on some microbial species under in vitro conditions [49][50][51][52][53]. While host factors, including genetic background and immune responses, also play important roles in CF pathogenesis, their contribution in shaping respiratory microbiota is not well studied.…”

Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients

“…Such interactions have been described for Scedosporium spp. and Pseudomonas aeruginosa (46). While direct contact with the bacteria resulted in fungal growth inhibition, the presence of P. aeruginosa could enhance the growth of the fungus when the two microorganisms were cultured "plate to plate" with a physical separation.…”

Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium

“…SCFM2 was further modified by the addition of p-aminobenzoic acid (PABA), nicotinamide adenine dinucleotide (NAD + ), adenine (ADE), guanine (GUA), xanthine (XAN), and hypoxanthine (HX) to generate SCFM3, as experimental results suggested that these metabolites are more available in CF sputum than in SCFM2 (11). We used PGM was used as the mucin source as it is a cost effective and common replacement of BSM (12)(13)(14).…”

“…Pulmonary mucus is a nutritionally distinct environmental niche comprised of mucin, DNA, amino acids, lipids, and micronutrients, including metals (1,2). To study the physiology of microbial pathogens and communities in the unique CF pulmonary environment, a variety of artificial sputum media (ASM) have been developed (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), and applied to investigate microbial physiology (3,5,(15)(16)(17), biofilm morphology (10,18), antibiotic susceptibility (19,20), and interspecies interactions in the context of CF (21)(22)(23). However, disparate nutrient concentration and bioavailability between ASM formulations may affect microbial growth, metabolism, and virulence (3,7,20,24).…”