{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:52:24Z","timestamp":1793145144799,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["RO1AI132638"],"award-info":[{"award-number":["RO1AI132638"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,4,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR)\n              <jats:italic>Candida glabrata<\/jats:italic>\n              blood isolates. ECR isolates are known to arise from a minor subpopulation of a clonal population, termed echinocandin persisters. Although it is believed that isolates with a higher echinocandin persistence (ECP) are more likely to develop ECR, the implication of ECP needs to be better understood. Moreover, replacing laborious and time-consuming traditional approaches to determine ECP levels with rapid, convenient, and reliable tools is imperative to advance our understanding of this emerging concept in clinical practice. Herein, using extensive\n              <jats:italic>ex vivo<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              systemic infection models, we showed that high ECP isolates are less effectively cleared by micafungin treatment and exclusively give rise to ECR colonies. Additionally, we developed a flow cytometry-based tool that takes advantage of a SYTOX-based assay for the stratification of ECP levels. Once challenged with various collections of echinocandin-susceptible blood isolates, our assay reliably differentiated ECP levels\n              <jats:italic>in vitro<\/jats:italic>\n              and predicted ECP levels in real time under\n              <jats:italic>ex vivo<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              conditions when compared to traditional methods relying on colony-forming unit counting. Given the high and low ECP predictive values of 92.3% and 82.3%, respectively, our assay showed a high agreement with traditional approach. Collectively, our study supports the concept of ECP level determination in clinical settings and provides a robust tool scalable for high-throughput settings. Application of this tool facilitates the interrogation of mutant and drug libraries to further our understanding of persister biology and designing anti-persister therapeutics.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Candida glabrata<\/jats:italic>\n              is a prevalent fungal pathogen able to replicate inside macrophages and rapidly develop resistance against frontline antifungal echinocandins. Multiple studies have shown that echinocandin resistance is fueled by the survival of a small subpopulation of susceptible cells surviving lethal concentrations of echinocandins. Importantly, bacterial pathogens that exhibit high antibiotic persistence also impose a high burden and generate more antibiotic-resistant colonies. Nonetheless, the implications of echinocandin persistence (ECP) among the clinical isolates of\n              <jats:italic>C. glabrata<\/jats:italic>\n              have not been defined. Additionally, ECP level determination relies on a laborious and time-consuming method, which is prone to high variation. By exploiting\n              <jats:italic>in vivo<\/jats:italic>\n              systemic infection and\n              <jats:italic>ex vivo<\/jats:italic>\n              models, we showed that\n              <jats:italic>C. glabrata<\/jats:italic>\n              isolates with a higher ECP are associated with a higher burden and more likely develop echinocandin resistance upon micafungin treatment. Additionally, we developed an assay that reliably determines ECP levels in real time. Therefore, our study identified\n              <jats:italic>C. glabrata<\/jats:italic>\n              isolates displaying high ECP levels as important entities and provided a reliable and convenient tool for measuring echinocandin persistence, which is extendable to other fungal and bacterial pathogens.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00072-24","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T13:05:10Z","timestamp":1710853510000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Echinocandin persistence directly impacts the evolution of resistance and survival of the pathogenic fungus\n            <i>Candida glabrata<\/i>"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-4841","authenticated-orcid":true,"given":"Amir","family":"Arastehfar","sequence":"first","affiliation":[{"name":"Division 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