Evaluation of outbreak persistence caused by multidrug-resistant and echinocandin-resistant Candida parapsilosis using multidimensional experimental and epidemiological approaches

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dc.authoridRyan, Adam/0000-0002-2593-2264
dc.authoridApostolopoulou, Anna/0000-0002-8874-0980
dc.contributor.authorDaneshnia, Farnaz
dc.contributor.authorFloyd, Daniel J.
dc.contributor.authorRyan, Adam P.
dc.contributor.authorGhahfarokhy, Pegah Mosharaf
dc.contributor.authorEbadati, Arefeh
dc.contributor.authorJusuf, Sebastian
dc.contributor.authorMunoz, Julieta
dc.date.accessioned2024-08-31T07:49:42Z
dc.date.available2024-08-31T07:49:42Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractCandida parapsilosis is known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant C. parapsilosis (MDR Cp) isolates were identified in a large Turkish hospital from 2017-2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital. The increasing number of MDR and ECR isolates contradicts the general principle that the severe fitness cost associated with these phenotypes could prevent their dominance in clinical settings. Here, we employed a multidimensional approach to systematically assess the fitness costs of MDR and ECR C. parapsilosis isolates. Whole-genome sequencing revealed a novel MDR genotype infecting two patients in 2022. Despite severe in vitro defects, the levels and tolerances of the biofilms of our ECR and MDR isolates were generally comparable to those of susceptible wild-type isolates. Surprisingly, the MDR and ECR isolates showed major alterations in their cell wall components, and some of the MDR isolates consistently displayed increased tolerance to the fungicidal activities of primary human neutrophils and were more immunoevasive during exposure to primary human macrophages. Our systemic infection mouse model showed that MDR and ECR C. parapsilosis isolates had comparable fungal burden in most organs relative to susceptible isolates. Overall, we observed a notable increase in the genotypic diversity and frequency of MDR isolates and identified MDR and ECR isolates potentially capable of causing persistent outbreaks in the future.en_US
dc.description.sponsorshipNational Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [R01AI132638, T32AI007061]; NIH National Institute of General Medical Sciences (NIGMS) [R35GM124594]; Kamangar familyen_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) awards R01AI132638 to M.K.M. and T32AI007061 to Anna Apostolopoulou, NIH National Institute of General Medical Sciences (NIGMS) award R35GM124594 to C.J.N., and from the Kamangar family in the form of an endowed chair to C.J.N. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.en_US
dc.identifier.doi10.1080/22221751.2024.2322655
dc.identifier.issn2222-1751
dc.identifier.issue1en_US
dc.identifier.pmid38380673en_US
dc.identifier.scopus2-s2.0-85186874598en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1080/22221751.2024.2322655
dc.identifier.urihttps://hdl.handle.net/11454/104970
dc.identifier.volume13en_US
dc.identifier.wosWOS:001180245400001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Ltden_US
dc.relation.ispartofEmerging Microbes & Infectionsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240831_Uen_US
dc.subjectMultidrug Resistanceen_US
dc.subjectEchinocandin Resistanceen_US
dc.subjectMannanen_US
dc.subjectChitinen_US
dc.subjectBeta-Glucanen_US
dc.titleEvaluation of outbreak persistence caused by multidrug-resistant and echinocandin-resistant Candida parapsilosis using multidimensional experimental and epidemiological approachesen_US
dc.typeArticleen_US

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