Exposure of Aspergillus fumigatus to Klebsiella pneumoniae Culture Filtrate Inhibits Growth and Stimulates Gliotoxin Production

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen capable of inducing chronic and acute infection in susceptible patients. A. fumigatus interacts with numerous bacteria that compose the microbiota of the lung, including Pseudomonas aeruginosa and Klebsiella pneumoniae, both of which are common isolates from cystic fibrosis sputum. Exposure of A. fumigatus to K. pneumoniae culture filtrate reduced fungal growth and increased gliotoxin production. Qualitative proteomic analysis of the K. pneumoniae culture filtrate identified proteins associated with metal sequestering, enzymatic degradation and redox activity, which may impact fungal growth and development. Quantitative proteomic analysis of A. fumigatus following exposure to K. pneumoniae culture filtrate (25% v/v) for 24 h revealed a reduced abundance of 1,3-beta-glucanosyltransferase (−3.97 fold), methyl sterol monooxygenase erg25B (−2.9 fold) and calcium/calmodulin-dependent protein kinase (−4.2 fold) involved in fungal development, and increased abundance of glutathione S-transferase GliG (+6.17 fold), non-ribosomal peptide synthase GliP (+3.67 fold), O-methyltransferase GliM (+3.5 fold), gamma-glutamyl acyltransferase GliK (+2.89 fold) and thioredoxin reductase GliT (+2.33 fold) involved in gliotoxin production. These results reveal that exposure of A. fumigatus to K. pneumoniae in vivo could exacerbate infection and negatively impact patient prognosis.

Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis

“…Prior in vitro and some in vivo laboratory studies focusing on the interplay between GNRs and Aspergillus species revealed pleiotropic (synergistic, neutral, or antagonistic) interactions that mediate interspecies competition between molds and GNR [6]. These interactions can result in altered fungal growth, viability, biofilm formation, toxin production, and invasive capacity [6,7]. Mechanistic determinants of inter-kingdom interplay include competition for nutrients and iron (e.g., through the production of siderophores) [8,9], secreted proteins [10], and the release of volatile compounds [11].…”