The present study examines the trend in distribution of Candida species and their antifungal resistance patterns in hospitals across Haryana, a North Indian state with poorly addressed epidemiology of fungal infections. In our collection of 228 Candida isolates, Candida albicans dominated in both high vaginal swab (HVS) and urine samples while Candida glabrata and Candida tropicalis were the second-highest non-albicans Candida species (NAC), respectively. Of note, in blood samples, C. tropicalis and C. albicans were present in equal numbers. All 228 isolates were subjected to antifungal susceptibility tests, whereby 51% of C. albicans recovered from HVS samples displayed fluconazole resistance. To understand its mechanistic basis, expression profiling of efflux pump genes CDR1, CDR2, MDR1 and azole drug target, ERG11 was performed in 20 randomly selected resistant isolates, wherein many isolates elicited higher expression. Further, ERG11 gene sequencing suggested that most of the isolates harbored mutations, which are not reported with azole resistance. However, one isolate, RPCA9 (MIC 64 μg/mL) harbored triple mutation (Y132C, F145L, A114V), wherein Y132 and F145 sites were previously implicated in azole resistance. Interestingly, one isolate, (RPCA61) having MIC > 128 μg/mL harbored a novel mutation, G129R. Of note, HVS isolates RPCA 21, RPCA 22, and RPCA 44 (MICs 64 to > 128 μg/mL) did not show any change in alteration in ERG11 or overexpression of efflux pump genes. Together, this study presents a first report of Candida infections in selected hospitals of Haryana State.
- MeSH
- antifungální látky farmakologie MeSH
- azoly farmakologie MeSH
- Candida albicans účinky léků genetika izolace a purifikace MeSH
- Candida klasifikace účinky léků genetika izolace a purifikace MeSH
- fungální léková rezistence genetika MeSH
- fungální proteiny genetika MeSH
- geny MDR genetika MeSH
- kandidóza epidemiologie mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- mutace MeSH
- nemocnice MeSH
- regulace genové exprese u hub MeSH
- retrospektivní studie MeSH
- systém (enzymů) cytochromů P-450 genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Indie MeSH
An imbalance in the redox homeostasis causes activation of multifaceted signaling responses which may be protective or deleterious. Amelioration of oxidative stress is one of the major modes of action of herbal supplements like Seabuckthorn (SBT). While the antioxidant potential of SBT is known, investigations into its effect on stress inducible signaling cascades are in progress. Here, we examine the impact of SBT on hypoxic tolerance and the mechanism behind its cardioprotective action. The efficacy of SBT was evaluated using the onset of gasping time (GT) at an altitude of 9754 m as the indicator for hypoxic tolerance. SBT led to a 100% increase in GT and curtailed hypoxia induced cardiac damage and free radical production. SBT upregulated HIF-1α and led to a two-fold increase in HO-1. A 100% increase in NO levels was observed. SBT reduced protein carbonylation and enhanced HSP70 levels. A statistically significant decline was seen in the markers of ER stress, GRP78, PERK and CHOP. SBT potentiated anti-inflammatory effects and downregulated NF-κB and TNF-α. Our study provides a novel insight into the mechanism behind the pro-survival effects of SBT against hypoxia, highlighting the cross talk between key adaptive responses mediated by HIF-1α and ER stress.
- MeSH
- antioxidancia terapeutické užití MeSH
- experimenty na zvířatech * MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa účinky léků MeSH
- financování organizované MeSH
- Hippophae * MeSH
- hypoxie MeSH
- kaspasy farmakologie MeSH
- laboratorní zvířata MeSH
- oxid dusnatý škodlivé účinky toxicita MeSH
- oxidační stres * účinky léků MeSH
- potkani Sprague-Dawley MeSH
- rostlinné přípravky terapeutické užití MeSH
- statistika jako téma MeSH
- volné radikály škodlivé účinky MeSH
- Check Tag
- mužské pohlaví MeSH
