Approaches by Rhodotorula mucilaginosa from a chronic kidney disease patient for elucidating the pathogenicity profile by this emergent species

Jarros, I. C.; Veiga, F. F.; Correa, J. L.; Barros, I. L. E.; Gadelha, M. C.; Voidaleski, M. F.; Pieralisi, N. E.; Pedroso, R. B.; Vicente, V. A.; Negri, M. E.; Svidzinski, T. I. E.

doi:10.1101/701052

bioRxiv · 10.1101/701052

Approaches by Rhodotorula mucilaginosa from a chronic kidney disease patient for elucidating the pathogenicity profile by this emergent species

Jarros, I. C.·Veiga, F. F.·Correa, J. L.·Barros, I. L. E.·Gadelha, M. C.·Voidaleski, M. F.·Pieralisi, N. E.·Pedroso, R. B.·Vicente, V. A.·Negri, M. E.·Svidzinski, T. I. E.

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Abstract

BackgroundTraditionally known as a common contaminant, Rhodotorula mucilaginosa is among the leading causes of invasive fungal infections by non-candida yeasts. They affect mainly immunocompromised individuals, often mimicking the cryptococcosis infection, despite invasive infections by Rhodotorula are still not well explained. Thus, here we aimed to characterize microbiologically clinical isolates of R. mucilaginosa isolated from colonization of a patient with chronic renal disease (CKD), as well as to evaluate their phylogeny, antifungal susceptibility, virulence, and pathogenicity in order to infer the potential to become a possible infection.\n\nMethodology/Principal FindingsFor this study, two isolates of R. mucilaginosa from oral colonization of a CKD patient were isolated, identified and characterized by classical (genotypic and phenotypic) methods. Susceptibility to conventional antifungals was evaluated, followed by biofilm production, measured by different techniques (total biomass, metabolic activity, colony forming units and extracellular matrix quantification). Finally, the pathogenicity of yeast was evaluated by infection of Tenebrio molitor larvae.\n\nAll isolates were resistant to azole and sensitive to polyenes and they were able to adhere and form biofilm on the abiotic surface of polystyrene. In general, similar profiles among isolates were observed over the observed periods (2, 24, 48 and 72 hours). Regarding extracellular matrix components of biofilms at different maturation ages, R. mucilaginosa was able to produce eDNA, eRNA, proteins, and polysaccharides that varied according to time and the strain. The death curve in vivo model showed a large reduction in the survival percentage of the larvae was observed in the first 24 hours, with only 40% survival at the end of the evaluation.\n\nConclusions/SignificanceWe infer that colonization of chronic renal patients by R. mucilaginosa offers a high risk of serious infection. And also emphasize that the correct identification of yeast is the main means for an efficient treatment.\n\nAuthor SummaryThe genus Rhodotorula is known to be a common contaminant, however, it has been increasing in the last years, reports of different forms infections by this yeast, reaching mainly individuals with secondary diseases or with low immunity. However, very little is known about the mechanism that triggers the disease. Thus, this study aims to characterize microbiologically clinical isolates of R. mucilaginosa isolated from a patient with chronic renal disease, as well as to evaluate their phylogeny, antifungal susceptibility, virulence, and pathogenicity in order to infer the potential to become a possible infection. It was possible to characterize in general the clinical isolates, to determine that they are resistant to an important class of the antifungal agents which are the azoles. In addition, they are able to adhere and to form biofilm on abiotic surfaces, this skill represents an important factor of virulence, which would guarantee their presence in medical devices, such as catheters, surfaces. These biofilm works as true reservoirs of these fungi disseminate and cause serious infections. This pathogenic potential was reinforced by a great reduction of survival in the larvae infected with this yeast. Therefore our results infer a high risk of infection to patients who are colonized by R. mucilaginosa.

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Jarros, I. C., Veiga, F. F., Correa, J. L., Barros, I. L. E., Gadelha, M. C., Voidaleski, M. F., Pieralisi, N. E., Pedroso, R. B., Vicente, V. A., Negri, M. E., Svidzinski, T. I. E.. 2019-07-12. Approaches by Rhodotorula mucilaginosa from a chronic kidney disease patient for elucidating the pathogenicity profile by this emergent species. https://doi.org/10.1101/701052

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