adhesion-candida-parapsilosis-to-bovine-serum-albumin-under-fluid

Adhesion of <em>Candida parapsilosis</em> to Bovine Serum Albumin under Fluid Shear

C. parapsilosis (Cp) is an emerging cause of bloodstream infections in certain populations. The&#160;Candida clade, including Cp, is increasingly ...

Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University

Mechanical ventilation plays a central role in the injury of premature lungs. However, the mechanisms by which mechanical signals trigger an inflammatory cascade to promote lung injury are not well-characterized. Transient receptor potential vanilloid 4 (TRPV4), a calcium-permeable mechanoreceptor channel has been shown to be a major determinant of ventilator-induced acute lung injury in adult models. However, the role of these channels as modulators of inflammation in immature lungs is unknown. In this study, we tested the hypothesis that TRPV4 channels are important mechanotransducers in fetal lung injury.

Mechanotransduction via TRPV4 regulates inflammation and differentiation in fetal mouse distal lung epithelial cells.

 has emerged as a frequent cause of invasive candidiasis with increasing evidence of unique biological features relative to  As it adapts to conditions within a mammalian host, rapid changes in gene expression are necessary to facilitate colonization and persistence in this environment. Adhesion of the organism to biological surfaces is a key first step in this process and is the focus of this study. Building on previous observations showing the importance of a member of the  gene family in  adhesion, three clinical isolates were cultured under two conditions that mimic the mammalian host and promote adhesion, incubation at 37°C in tissue culture medium 199 or in human plasma. Transcriptional profiles using RNA-seq were obtained in these adhesion-inducing conditions and compared to profiles following growth in yeast media that suppress adhesion to identify gene expression profiles associated with adhesion. Overall gene expression profiles among the three strains were similar in both adhesion-inducing conditions and distinct from adhesion-suppressing conditions. Pairwise analysis among the three growth conditions identified 133 genes that were differentially expressed at a cutoff of ±4-fold, with the most upregulated genes significantly enriched in iron acquisition and transmembrane transport, while the most downregulated genes were enriched in oxidation-reduction processes. Gene family enrichment analysis identified gene families with diverse functions that may have an important role in this important step for colonization and disease. Invasive  infections are frequent complications of the immunocompromised and are associated with substantive morbidity and mortality. Although  is the best-studied species, emerging infections by non- species have led to increased efforts to understand aspects of their pathogenesis that are unique from  is a frequent cause of invasive infections, particularly among premature infants. Recent efforts have identified important virulence mechanisms that have features distinct from  can exist outside a host environment and therefore requires rapid modifications when it encounters a mammalian host to prevent its clearance. An important first step in the process is adhesion to host surfaces. This work takes a global, nonbiased approach to investigate broad changes in gene expression that accompany efficient adhesion. As such, biological pathways and individual protein targets are identified that may be amenable to manipulation to reduce colonization and disease from this organism.

Sunil K. Shaw

Women & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown University

Adhesion of Candida parapsilosis to Bovine Serum Albumin under Fluid Shear