Genomic analyses reveal high diversity and rapid evolution of Pichia kudriavzevii within a neonatal intensive care unit in Delhi, India
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PROVIDER: PRJNA1186670 | ENA |
REPOSITORIES: ENA
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Project description:Pichia kudriavzevii causes life-threatening infections in immune compromised hosts including hospitalized neonates. This pathogen is resistant to fluconazole while uncommon, strains resistant to multiple antifungal drugs voriconazole, amphotericin B and echinocandins have been reported in healthcare environments. Understanding how P. kudriavzevii spread, persist, and adapt to healthcare settings could help us develop better management strategies. In this study, whole genome sequencing identifies multiple outbreaks of bloodstream infections caused by P. kudriavzevii in a single neonatal intensive care unit (NICU) over five years. Interestingly, two genetically diverse clusters of P. kudriavzevii population showed frequent loss of heterozygosity (LOH) events between two temporal samples. The first outbreak cluster (during 2015-16) showed LOH at chromosomes 1, 4 and 5 and the other outbreak cluster (year 2020) exhibited marked LOH at chromosome 2. The circulation of two separate strain clusters of P. kudriavzevii suggests nosocomial transmission in the NICU in different time periods. Further, to evaluate the gene expression difference between isolates from two clusters, we compared the transcriptomic profiles of three isolates of cluster I and II and exhibiting distinct fluconazole MICs. While no difference was found at the azole target gene ERG11 or the ATP-binding cassette (ABC) transporter genes, differences in transcript abundance were found between the two isolates in genes coding for cell division and filamentation, repressor of ABC gene, FCR1 and ERG5 gene involved in ergosterol biosynthesis pathway. Our study indicates significant diversity, persistence, and rapid evolution of P. kudriavzevii within a single NICU.
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Project description:We determined whether we could identify clusters of children with critical asthma by plasma cytokine concentration. Differences in gene expression between the two clusters were analyzed using a targeted Nanostring immunology array. We performed a single-center, prospective, observational cohort study of 64 children ages 6 – 17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021.
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2018-08-22 | PXD004001 | Pride
Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
2012-05-12 | GSE37944 | GEO
Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days. A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) M-NM-1-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80M-BM-0C. RNA was extracted.
2012-05-11 | E-GEOD-37944 | biostudies-arrayexpress
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