Synergy Between Pseudomonas aeruginosa Filtrates And Voriconazole Against Aspergillus fumigatus Biofilm Is Less for Mucoid Isolates From Persons With Cystic Fibrosis

Abstract

Persons with cystic fibrosis (CF) frequently suffer from Pseudomonas aeruginosa and Aspergillus fumigatus co-infections. There is evidence that co-infections with these interacting pathogens cause airway inflammation and aggravate deterioration of lung function. We recently showed that P. aeruginosa laboratory isolates synergistically interact with the anti-fungal azole voriconazole (VCZ), inhibiting biofilm metabolism of several A. fumigatus laboratory strains. Interaction was usually mediated via pyoverdine, but also via pyocyanin or pyochelin. Here we used planktonic filtrates of 7 mucoid and 9 non-mucoid P. aeruginosa isolates from CF patients, as well as 8 isolates without CF origin, and found that all of these isolates interacted with VCZ synergistically at their IC50 as well as higher dilutions. CF mucoid isolates showed the weakest interactive effects. Four non-mucoid P. aeruginosa CF isolates produced no or very low levels of pyoverdine and did not reach an IC50 against forming A. fumigatus biofilm; interaction with VCZ still was synergistic. A VCZ-resistant A. fumigatus strain showed the same level of susceptibility for P. aeruginosa anti-fungal activity as a VCZ-susceptible reference strain. Filtrates of most Pseudomonas isolates were able to increase anti-fungal activity of VCZ on a susceptible A. fumigatus strain. This was also possible for the VCZ-resistant strain. In summary these data show that clinical P. aeruginosa isolates, at varying degrees, synergistically interact with VCZ, and that pyoverdine is not the only molecule responsible. These data also strengthen the idea that during co-infections of A. fumigatus and P. aeruginosa lower concentrations of VCZ might be sufficient to control fungal growth.

Scedosporium/Lomentospora Species Induce the Production of Siderophores by Pseudomonas aeruginosa in a Cystic Fibrosis Mimic Environment

“…The fungal growth inhibition occurs mainly due to the bacterial secreted molecules, such as phenazines (e.g., pyocyanin, 1-hydroxyphenazine), quorumsensing compounds (e.g., acyl-homoserine lactones and alkyl quinolones), dirhamnolipids and siderophores (e.g., pyoverdine and pyochelin) [25,[37][38][39]. Studies concerning the inhibitory effect of molecules produced by P. aeruginosa on fungal growth are mainly performed with purified commercial compounds and/or P. aeruginosa pure culture supernatant [14,15,28,34,36,40,41]; the studies with molecules produced in co-culture with fungi are scarce [20,42]. Nevertheless, the interaction between microorganisms leads to a differential production of extracellular molecules [20,42].…”

Virtual Screening of Potential RoxS Inhibitors and Evaluation of Their Antimicrobial Activity in Combination with Antibiotics against Clinically Resistant Bacteria

“…The airways of patients with cystic fibrosis are susceptible to colonization by various microorganisms, particularly Aspergillus fumigatus and P. aeruginosa [ 44 , 45 ]. Mixed microbial infections usually occur in the lungs and can lead to airway inflammation and the worsening of lung function [ 46 , 47 ]. PCZ is useful in the treatment of Aspergillus-associated cystic fibrosis [ 48 ].…”

Simple method for quantification of anionic biosurfactants in aqueous solutions

“…A variety of microorganisms produce surface-active agents to solubilize and use hydrophobic substances, such as oils or hydrocarbons, as carbon sources ( Saeed et al, 2022 ; Sah et al, 2022 ), to promote group surface behaviour ( Nielsen et al, 2002 ; Tremblay et al, 2007 ; Kearns, 2010 ; Nickzad et al, 2015 ; Morin et al, 2022 ) and act as antagonistic ( Zulianello et al, 2006 ; Sidrim et al, 2020 ; Sass et al, 2021 ; Sass et al, 2022 ) and virulence factors ( Zulianello et al, 2006 ; Köhler et al, 2010 ).…”