Anti-Fungal () Activity of in Cystic Fibrosis Synthetic Sputum.

(Af) and (Pa) are pathogens inhabiting the lungs of persons with cystic fibrosis (CF), or immune-compromised patients, causing or aggravating disease. We previously investigated their microbial interaction as well as susceptibility to anti-fungal drugs using RPMI medium (contains undetectable iron concentrations), as is standard for susceptibility testing. Here we investigated microbial interaction in synthetic sputum medium (SSPM), a complex mixture designed to mimic the milieu in CF lungs.

The Expanding Mycovirome of .

Mycoviruses are viruses that infect fungi and are widespread across all major fungal taxa, exhibiting great biological diversity. Since their discovery in the 1960s, researchers have observed a myriad of fungal phenotypes altered due to mycoviral infection. In this review, we examine the nuanced world of mycoviruses in the context of the medically and agriculturally important fungal genus, .

Simple method for quantification of anionic biosurfactants in aqueous solutions.

Biosurfactants are microbial products that have applications as cleaning agents, emulsifiers, and dispersants. Detection and quantification of biosurfactants can be done by various methods, including colorimetric tests, high performance liquid chromatography (HPLC) coupled to several types of detectors, and tests that take advantage of biosurfactants reducing surface tension of aqueous liquids, allowing for spreading and droplet formation of oils. We present a new and simple method for quantifying biosurfactants by their ability, on paper, to reduce surface tension of aqueous solutions, causing droplet dispersion on an oiled surface in correlation with biosurfactant content.

Protective role of CFTR during fungal infection of cystic fibrosis bronchial epithelial cells with .

Lung infection with the fungus Af is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function. We established a fungal epithelial co-culture model to examine the impact of Af infection on CF bronchial epithelial barrier function using Af strains 10AF and AF293-GFP, and the CFBE41o- cell line homozygous for the F508del mutation with (CF) and without (CF) normal CFTR expression. Following exposure of the epithelial surface to Af conidia, formation of germlings (early stages of fungal growth) was detected after 9-12 hours and hyphae (mature fungal growth) after 12-24 hours.

AfuPmV-1-Infected Is More Susceptible to Stress Than Virus-Free Fungus.

Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) affects Af293's growth in vitro, iron metabolism, resistance in intermicrobial competition with , resistance to osmotic stress, and resistance to the chitin synthase inhibitor nikkomycin Z. Here, we show that response to high temperature, Congo Red-induced stress, and hydrogen peroxide are also dependent on the viral infection status of . AfuPmV-1- infected Af293 was more susceptible than virus-free Af293 to growth inhibition by high temperature, hydrogen peroxide, Congo Red exposure, and nutrient restriction.

Virus Infection Impairs Fungal Response to Stress: Effect of Salt.

Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) weakens the resistance of biofilms of common reference strain Af293 in intermicrobial competition with , and sensitizes for antifungal effects of nikkomycin Z. We compared the sensitivity of two virus-infected (VI) and one virus-free (VF) Af293 strains to hypertonic salt. Salt stress impairs the growth of VI and VF at all times; VF control growth always exceeds VI, and VF growth in salt always exceeds VI.

Continuous dosing of nikkomycin Z against systemic candidiasis, in vivo and in vitro correlates.

Background: Candidiasis is the most common cause of fungal sepsis, and new agents are of interest to ameliorate current deficiencies in therapy. Nikkomycin Z (NIKZ) is an inhibitor of chitin synthase, interfering with fungal cell wall development.

Objectives/methods: We studied NIKZ therapy of disseminated murine candidiasis, via continuous drug exposure, in drinking water, to compensate for rapid clearance of the drug.

Polymycovirus Infection Sensitizes for Antifungal Effects of Nikkomycin Z.

Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) weakens resistance of common reference strain Af293 biofilms in intermicrobial competition with . We compared the sensitivity of two infected and one virus-free Af293 strains to antifungal drugs. All three were comparably sensitive to drugs affecting fungal membranes (voriconazole, amphotericin) or cell wall glucan synthesis (micafungin, caspofungin).

Synergy Between Filtrates And Voriconazole Against Biofilm Is Less for Mucoid Isolates From Persons With Cystic Fibrosis.

Persons with cystic fibrosis (CF) frequently suffer from and 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 laboratory isolates synergistically interact with the anti-fungal azole voriconazole (VCZ), inhibiting biofilm metabolism of several laboratory strains.

Metrics of Antifungal Effects of Ciprofloxacin on Planktonic Growth and Biofilm Metabolism; Effects of Iron and Siderophores.

and frequently coexist in the airways of immunocompromised patients or individuals with cystic fibrosis. Ciprofloxacin (CIP) is a synthetic quinolone antibiotic commonly used to treat bacterial infections, such as those produced by CIP binds iron, and it is unclear what effect this complex would have on the mycobiome. The effects of CIP on were dependent on the iron levels present, and on the presence of siderophores.

Altered Strategies to Inhibit Surface Colonies.

and infections frequently co-localize in lungs of immunocompromised patients and individuals with cystic fibrosis (CF). The antifungal activity of has been described for its filtrates. Pyoverdine and pyocyanin are the principal antifungal molecules active against biofilm metabolism present in iron-limited or iron-replete planktonic culture filtrates, respectively.

Efficacy of nikkomycin Z in murine CNS coccidioidomycosis: modelling sustained-release dosing.

Objectives: Meningitis is the most feared coccidioidomycosis complication. Nikkomycin Z (nikZ) is a chitin synthase inhibitor. A concern is short half-life, necessitating multiple dose/day regimens.

Nikkomycin Z against Disseminated Coccidioidomycosis in a Murine Model of Sustained-Release Dosing.

Nikkomycin Z (nikZ) is a chitin synthase inhibitor. Efficacy against has been demonstrated in animal models of pulmonary or brain infection. Its short half-life in mice and in humans would necessitate divided daily dosing.

Virulence Factors Support Voriconazole Effects on .

and are pathogens that are associated with deterioration of lung function, e.g., in persons with cystic fibrosis (CF).

Molecular Modifications of the Pseudomonas Quinolone Signal in the Intermicrobial Competition with .

The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule for that regulates virulence factors, chelates iron, and is an important factor in interactions with eukaryotes, including fungi and mammalian hosts. It was previously shown to inhibit or boost , depending on the milieu iron concentration. We studied several molecular modifications of the PQS molecule, and their effects on biofilm metabolism and growth in vitro, and the effects of iron supplementation.

Virus Infection of Compromises the Fungus in Intermicrobial Competition.

and compete in nature, and are the commonest bacterial and fungal pathogens in some clinical settings, such as the cystic fibrosis lung. Virus infections of fungi occur naturally. Effects on fungal physiology need delineation.

Efficacy and Associated Drug Exposures of Isavuconazole and Fluconazole in an Experimental Model of Coccidioidomycosis.

spp. are important pathogens in regions where they are endemic, and new treatment options are needed. Here, isavuconazonium sulfate (ISAVUSULF) and fluconazole (FLU) were evaluated in experimental disseminated coccidioidomycosis to characterize drug exposures associated with efficacy.

Live imaging and quantitative analysis of growth and morphology during inter-microbial interaction with .

(PA) and (AF) chronically colonize the airways of patients with cystic fibrosis or chronic immunosuppression and mutually affect each other's pathogenesis. Here, we evaluated IncuCyte time-lapse imaging and NeuroTrack (NT) analysis (Wurster et al., 2019, mBio) as a toolbox to study mycelial expansion and morphogenesis of AF during interaction with PA.

Diphenyl diselenide and its interaction with antifungals against Aspergillus spp.

Unlabelled: Given the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of diphenyl diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates.

Under nonlimiting iron conditions pyocyanin is a major antifungal molecule, and differences between prototypic Pseudomonas aeruginosa strains.

Airways of immunocompromised patients, or individuals with cystic fibrosis (CF), are common ground for Pseudomonas aeruginosa and Aspergillus fumigatus infections. Hence, in such a microenvironment both pathogens compete for resources. While under limiting iron conditions the siderophore pyoverdine is the most effective antifungal P.

Comparative Study of Newer and Established Methods of Diagnosing Coccidioidal Meningitis.

Meningitis is the most devastating form of coccidioidomycosis. A convenient, rapid diagnostic method could result in early treatment and avoid many meningitis complications. We studied cerebrospinal fluid (CSF) samples in patients with documented coccidioidal meningitis, and controls, with complement fixation (CF), immunodiffusion (ID) (the "classical" assays), lateral flow assays (LFA; one-strip and two-strip), and two enzyme immunoassays (EIA).

Is Inhibited by Volatiles.

Background: (Pa) and (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons with cystic fibrosis, particularly the airways. These intermicrobial studies have largely been conducted in liquid medium or on agar, and thus focus on soluble or diffusible microbial products.

Review of Potential Weaponry, Relevant to the Interplay, for the Mycology Community.

is one of the most prominent opportunistic bacteria in airways of cystic fibrosis patients and in immunocompromised patients. These bacteria share the same polymicrobial niche with other microbes, such as the opportunistic fungus Their inter-kingdom interactions and diverse exchange of secreted metabolites are responsible for how they both fare in competition for ecological niches. The outcomes of their contests likely determine persistent damage and degeneration of lung function.

The Pseudomonas aeruginosa product pyochelin interferes with Trypanosoma cruzi infection and multiplication in vitro.

Background: Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease.

Methods: Vero cells were infected with T.