The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance in Candida albicans.

IF 3.1 Q2 MICROBIOLOGY
Marina Druseikis, Austin Mottola, Judith Berman
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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.

敏感性代谢:清除白色念珠菌耐受和耐药之间的FoG。
综述的目的:抗真菌治疗的失败是令人震惊的常见患者感染白色念珠菌分离,测试为敏感的体外。这意味着临床敏感性试验对治疗成功的预测价值有限。为了指导患者预后的改善,我们必须了解环境和代谢状态对药物反应的影响。最近的研究发现:实验室条件经常偏离宿主环境,目前的药敏试验标准忽略了生长缓慢的耐受性表型;这两个因素都可能导致抗真菌治疗失败。代谢组学研究表明,菌株背景、营养可利用性和药物暴露影响白色念珠菌细胞的代谢状态;同样,代谢状态影响药物敏感性。摘要:临床鉴定耐药菌株可改善患者预后。分析必需但有限的营养物质的影响的研究有可能改善对持久性念珠菌病的避免,并减少抗真菌治疗失败的频率。在这里,我们重点介绍了探讨药物暴露和抗真菌药物耐药状态对白色念珠菌代谢组的影响的文献。需要对抗真菌药物耐受性进行类似的分析。此外,我们关注四种基本小分子——铁、锌、磷酸盐和鞘脂——与抗真菌耐受性和耐药性的生物学相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.50
自引率
1.90%
发文量
9
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.
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