The incidence of fungal infections is increasing at an alarming rate, presenting an enormous challenge to healthcare professionals. This increase is directly related to the growing population of immunocompromised individuals, resulting from changes in medical practice such as the use of intensive chemotherapy and immunosuppressive drugs. HIV and other diseases which cause immunosuppression have also contributed to this problem. Superficial and subcutaneous fungal infections affect the skin, keratinous tissues and mucous membranes. Included in this class are some of the most frequently occurring skin diseases, affecting millions of people worldwide. Although rarely life threatening, they can have debilitating effects on a person's quality of life and may in some circumstances spread to other individuals or become invasive. Most superficial and subcutaneous fungal infections are easily diagnosed and readily amenable to treatment. Systemic fungal infections may be caused by either an opportunistic organism that infects an at-risk host, or may be associated with a more invasive organism that is endemic to a specific geographical area. Systemic infections can be life threatening and are associated with high morbidity and mortality. Because diagnosis is difficult and the causative agent is often confirmed only at autopsy, the exact incidence of systemic infections is difficult to determine. The most frequently encountered pathogens are Candida albicans and Aspergillus spp. but other fungi such as non-albicans Candida spp. are increasingly important.
"Occurrence of pathogenic fungi infections has increased rapidly. This is directly related to the increasing population of immune-compromised people in connection with the use of antibiotics. "
[Show abstract][Hide abstract] ABSTRACT: Due to the increasing demand for new pharmaceuticals showing biological activity against pathogenic microorganisms, there is increasing search for new compounds with predicted biological activity. Variously substituted thioamide derivatives with 1.3 and 1.2 ring of thiazole and 1,3,4-thiadiazole, as well as pyrazole were assessed for their activity against Candida albicans. Activity of majority of tested thioamides was larger as compared with that of the reference drugs. The electron parameters of obtained N-heterocyclic thioamides were determined and dependencies on their biological activity against Candida albicans were studied. The best electron compliance of produced bindings with the activity against Candida albicans was observed for the derivatives containing 1,3,4-thiadiazole ring.
The Indian journal of pharmacy 09/2014; 76(4):287-298. · 0.73 Impact Factor
"e l s e v i e r . c o m / l o c a t e / y b b r c  . Like other living cells, C. albicans cannot avoid the frequent challenge of oxidative stress by phagocytes when it survives and causes diseases in host . "
[Show abstract][Hide abstract] ABSTRACT: The type II Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are thought to play a vital role in cellular regulation in mammalian cells. Two genes CMK1 and CMK2 in the Candida albicans genome encode homologues of mammalian CaMKs. In this work, we constructed the cmk1Δ/Δ, the cmk2Δ/Δ and the cmk1Δ/Δcmk2Δ/Δ mutants and found that CaMKs function in cell wall integrity (CWI) and cellular redox regulation. Loss of either CMK1 or CMK2, or both resulted in increased expression of CWI-related genes under Calcofluor white (CFW) treatment. Besides, CaMKs are essential for the maintenance of cellular redox balance. Disruption of either CMK1 or CMK2, or both not only led to a significant increase of intracellular ROS levels, but also led to a decrease of the mitochondrial membrane potential (MMP), suggesting the important roles that CaMKs play in the maintenance of the mitochondrial function.
Biochemical and Biophysical Research Communications 03/2014; 446(4). DOI:10.1016/j.bbrc.2014.03.059 · 2.30 Impact Factor
"Candida albicans (C albicans), a major human fungal pathogen, causes disorders ranging from mild infections to life-threatening diseases1, 2. C albicans is often treated with fluconazole, which is a fungistatic drug. "
[Show abstract][Hide abstract] ABSTRACT: Widespread and repeated use of azoles, particularly fluconazole, has led to the rapid development of azole resistance in Candida albicans. We investigated the role of CaIPF14030 during the development of azole resistance in C albicans.
The expression of CaIPF14030 was measured by quantitative RT-PCR, and CaIPF14030 was disrupted by the hisG-URA3-hisG (URA-blaster) method. The sensitivity of C albicans to azoles was examined using a spot assay, and the intracellular ATP concentrations were measured by a luminometer.
CaIPF14030 expression in C albicans was up-regulated by Ca(2+) in a calcineurin-dependent manner, and the protein was overexpressed during the stepwise acquisition of azole resistance. However, disruption or ectopic overexpression of CaIPF14030 did not affect the sensitivity of C albicans to azoles. Finally, we demonstrated that disruption of CaIPF14030 significantly increased intracellular ATP levels, and overexpression significantly decreased intracellular ATP levels in C albicans.
CaIPF14030 may negatively modulate intracellular ATP levels during the development of azole resistance in C albicans.
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