{"title":"The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in <i>Candida albicans</i>.","authors":"Marina Druseikis, Austin Mottola, Judith Berman","doi":"10.1007/s40588-023-00189-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Failure of antifungal treatment is alarmingly common in patients infected with <i>Candida albicans</i> isolates that test as susceptible in vitro. This means that clinical susceptibility tests have limited predictive value for treatment success. To guide the improvement of patient outcomes, we must understand the effects of environmental and metabolic states on drug responses.</p><p><strong>Recent findings: </strong>Lab conditions often deviate from host environments, and current susceptibility testing standards ignore slow-growing, tolerant phenotypes; both factors may contribute to antifungal treatment failure. Metabolomic studies reveal that strain background, nutrient availability, and drug exposure influence the metabolic state of <i>C</i>. <i>albicans</i> cells; similarly, the metabolic state influences drug susceptibility.</p><p><strong>Summary: </strong>Identifying tolerant strains in the clinic may improve patient outcomes. Studies that analyze the effects of essential but limited nutrients have the potential to improve the avoidance of persistent candidiasis and to reduce the frequency of antifungal treatment failures. Here, we highlight literature that explores the effect of drug exposure and antifungal drug resistance status on the <i>C</i>. <i>albicans</i> metabolome. Similar analyses need to be carried out relative to antifungal drug tolerance. Additionally, we focus on the biological relevance of four essential small molecules-iron, zinc, phosphate, and sphingolipids-to antifungal tolerance and resistance.</p>","PeriodicalId":45506,"journal":{"name":"Current Clinical Microbiology Reports","volume":"10 2","pages":"36-46"},"PeriodicalIF":3.1000,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614596/pdf/EMS176254.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Clinical Microbiology Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40588-023-00189-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: Failure of antifungal treatment is alarmingly common in patients infected with Candida albicans isolates that test as susceptible in vitro. This means that clinical susceptibility tests have limited predictive value for treatment success. To guide the improvement of patient outcomes, we must understand the effects of environmental and metabolic states on drug responses.
Recent findings: Lab conditions often deviate from host environments, and current susceptibility testing standards ignore slow-growing, tolerant phenotypes; both factors may contribute to antifungal treatment failure. Metabolomic studies reveal that strain background, nutrient availability, and drug exposure influence the metabolic state of C. albicans cells; similarly, the metabolic state influences drug susceptibility.
Summary: Identifying tolerant strains in the clinic may improve patient outcomes. Studies that analyze the effects of essential but limited nutrients have the potential to improve the avoidance of persistent candidiasis and to reduce the frequency of antifungal treatment failures. Here, we highlight literature that explores the effect of drug exposure and antifungal drug resistance status on the C. albicans metabolome. Similar analyses need to be carried out relative to antifungal drug tolerance. Additionally, we focus on the biological relevance of four essential small molecules-iron, zinc, phosphate, and sphingolipids-to antifungal tolerance and resistance.
期刊介绍:
Current Clinical Microbiology Reports commissions expert reviews from leading scientists at the forefront of research in microbiology. The journal covers this broad field by dividing it into four key main areas of study: virology, bacteriology, parasitology, and mycology. Within each of the four sections, experts from around the world address important aspects of clinical microbiology such as immunology, diagnostics, therapeutics, antibiotics and antibiotic resistance, and vaccines. Some of the world’s foremost authorities in the field of microbiology serve as section editors and editorial board members. Section editors select topics for which leading researchers are invited to contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, which are highlighted in annotated reference lists. These timely reviews of the literature examine the latest scientific discoveries and controversies as they emerge and are indispensable to both researchers and clinicians. The editorial board, composed of more than 20 internationally diverse members, reviews the annual table of contents, ensures that topics address all aspects of emerging research, and where applicable suggests topics of critical importance to various countries/regions.