Jain Kusum, Wang Yue, Jain Peeyush, Kalita Barsha, Shivarathri Raju, Chauhan Manju, Kaur Hardeep, Chauhan Neeraj, Xu Jianping, Chowdhary Anuradha
Medical Mycology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Department of Zoology, Ramjas College, University of Delhi, Delhi, India.
Antimicrob Agents Chemother. 2025 Mar 5;69(3):e0170924. doi: 10.1128/aac.01709-24. Epub 2025 Jan 24.
causes life-threatening infections in immunocompromised hosts, including hospitalized neonates. This pathogen is intrinsically resistant to fluconazole, while uncommon strains resistant to multiple antifungal drugs, including voriconazole, amphotericin B, and echinocandins, have also been reported from healthcare environments. Thus, understanding how spread, persist, and adapt to healthcare settings could help us develop better infection management strategies. In this study, whole genome sequencing identifies multiple outbreaks of bloodstream infections in a single neonatal intensive care unit (NICU) over 5 years caused by genetically diverse strains of . Interestingly, two genetically distinct clusters of strains showed frequent loss of heterozygosity (LOH) events between two temporal samples. The first outbreak cluster (2015-2016) showed LOH at chromosomes 1, 4, and 5, and the other outbreak cluster (2020) exhibited LOH at chromosome 2. The circulation of two separate strain clusters of suggests nosocomial transmission in the NICU in different time periods. Furthermore, we compared the transcriptomic profiles of three isolates of clusters I and II that exhibited distinct fluconazole and itraconazole MICs. While no significant difference in gene expression was found at the azole-target gene or the ATP-binding cassette (ABC) transporter genes, such differences were found in genes involved in cell division and filamentation, such as (sirtuin deacetylase) and (replication factor A). Interestingly, increased filamentation was observed in clade I isolate exhibiting high fluconazole MICs. Together, our study indicates significant diversity, persistence, and rapid evolution of within a single NICU.
在免疫功能低下的宿主中引发危及生命的感染，包括住院新生儿。这种病原体对氟康唑具有内在抗性，同时在医疗环境中也报告了对多种抗真菌药物耐药的罕见菌株，这些药物包括伏立康唑、两性霉素B和棘白菌素。因此，了解其如何在医疗环境中传播、持续存在并适应环境，有助于我们制定更好的感染管理策略。在本研究中，全基因组测序确定了5年间在一个新生儿重症监护病房（NICU）由基因多样的菌株引起的多起血流感染暴发。有趣的是，两个基因不同的菌株簇在两个时间样本之间显示出频繁的杂合性缺失（LOH）事件。第一个暴发簇（2015 - 2016年）在染色体1、4和5上出现LOH，另一个暴发簇（2020年）在染色体2上出现LOH。两个不同菌株簇的循环表明NICU在不同时间段存在医院内传播。此外，我们比较了表现出不同氟康唑和伊曲康唑最低抑菌浓度（MIC）的I簇和II簇的三个分离株的转录组谱。虽然在唑类靶基因或ATP结合盒（ABC）转运蛋白基因上未发现基因表达的显著差异，但在参与细胞分裂和丝状化的基因中发现了差异，如（沉默调节蛋白脱乙酰酶）和（复制因子A）。有趣的是，在表现出高氟康唑MIC的I分支分离株中观察到丝状化增加。总之，我们的研究表明在单个NICU内存在显著的多样性、持续性和快速进化。
