Genomic landscape of the DHA1 family in Candida auris and mapping substrate repertoire of CauMdr1.

The last decade has witnessed the rise of an extremely threatening healthcare-associated multidrug-resistant non-albicans Candida (NAC) species, Candida auris. Since besides target alterations, efflux mechanisms contribute maximally to antifungal resistance, it is imperative to investigate their contributions in this pathogen. Of note, within the major facilitator superfamily (MFS) of efflux pumps, drug/H+ antiporter family 1 (DHA1) has been established as a predominant contributor towards xenobiotic efflux. Our study provides a complete landscape of DHA1 transporters encoded in the genome of C. auris. This study identifies 14 DHA1 transporters encoded in the genome of the pathogen. We also construct deletion and heterologous overexpression strains for the most important DHA1 drug transporter, viz., CauMdr1 to map the spectrum of its substrates. While the knockout strain did not show any significant changes in the resistance patterns against most of the tested substrates, the ortholog when overexpressed in a minimal background Saccharomyces cerevisiae strain, AD1-8u-, showed significant enhancement in the minimum inhibitory concentrations (MICs) against a large panel of antifungal molecules. Altogether, the present study provides a comprehensive template for investigating the role of DHA1 members of C. auris in antifungal resistance mechanisms. KEY POINTS: • Fourteen putative DHA1 transporters are encoded in the Candida auris genome. • Deletion of the CauMDR1 gene does not lead to major changes in drug resistance. • CauMdr1 recognizes and effluxes numerous xenobiotics, including prominent azoles.

Exploring Haematological Complications in Cirrhosis of the Liver: A Comprehensive Review.

Various chronic liver diseases inevitably end up with cirrhosis of the liver, and this comes with a whole range of haematological complications. Therefore, this detailed review has discussed pathophysiology, clinical manifestations, diagnostic measures, and treatment plans for these anomalies. Closely related are conditions such as anaemia, thrombocytopenia, coagulopathy, leukopenia, and haemolytic disorders, which are known to contribute to morbidity and mortality in cirrhotic patients significantly. Therefore, we need to understand the causes of these problems to find ways of helping our patients better. For this reason, multidisciplinary management will be key in ensuring proper monitoring, timely intervention, and preventive measures for haematological abnormalities in cirrhosis. Additionally, there have been tremendous advancements in therapeutic options, like adjunctive therapies or haematopoietic growth factors, which hold much promise regarding patient outcomes. This article emphasizes the proactive management of haematological complications associated with cirrhosis while highlighting the need for further research coupled with collaboration aimed at strengthening prevention strategies, diagnostic methods, and curative interventions.