Recent progress in medical sciences and therapy resulted in an increased number of immunocompromised individuals. Candida albicans is the leading opportunistic fungal pathogen causing infections in humans, ranging from superficial mucosal lesions to disseminated or bloodstream candidiasis. Superficial candidiasis not always presents a risk to the life of the infected host, however it significantly lowers the quality of life. Superficial Candida infections are difficult to treat and their frequency of occurrence is currently rising. To implement successful treatment doctors should be up to date with better understanding of C. albicans resistance mechanisms. Despite high frequency of Candida infections there is a limited number of antimycotics available for therapy. This review focuses on current understanding of the mode of action and resistance mechanisms to conventional and emerging antifungal agents for treatment of superficial and mucosal candidiasis.

Scanning electron microscope (SEM) observations were used to analyze particular morphologies of Candida albicans clinical isolate (strain 82) and mutants defective in hyphae-promoting genes EFG1 (strain HLC52) and/or CPH1 (strains HLC54 and Can16). Transcription factors Efg1 and Cph1 play role in regulating filamentation and adhesion of C. albicans’ morphologies. Comparative analysis of such mutants and clinical isolate showed that Efg1 is required for human serum-induced cell growth and morphological switching. In the study, distinct differences between ultrastructural patterns of clinical strain’s and null mutants’ morphologies were observed (spherical vs tube-like blastoconidia, or solid and fragile constricted septa vs only the latter observed in strains with EFG1 deleted). In addition, wild type strain displayed smooth colonies of cells in comparison to mutants which exhibited wrinkled phenotype. It was observed that blastoconidia of clinical strain exhibited either polarly or randomly located budding. Contrariwise, morphotypes of mutants showed either multiple polar budding or a centrally located single bud scar (mother-daughter cell junction) distinguishing tube-like yeast/pseudohyphal growth (the length-to-width ratios larger than 1.5). In their planktonic form of growth, blastoconidia of clinical bloodstream isolate formed constitutively true hyphae under undiluted human serum inducing conditions. It was found that true hyphae are essential elements for developing structural integrity of conglomerate, as mutants displaying defects in their flocculation and conglomerate-forming abilities in serum. While filamentation is an important virulence trait in C. albicans the true hyphae are the morphologies which may be expected to play a role in bloodstream infections.

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A b s t r a c tPenicillin G oversecretion by Penicillium chrysogenum PQ96 is associated with a strictly adjusted cellular organization of the mature and senescent mycelial cells. Abundant vacuolar phagy and extended cellular vacuolization combined with vacuolar budding resulting in the formation of vacuolar vesicles that fuse with the cell membrane are the most important characteristic features of those cells. We suggest as follows: if the peroxisomes are integrated into vacuoles, the penicillin G formed in peroxisomes might be transferred to vacuoles and later secreted out of the cells by an exocytosis process. The peroxisomal cells of the mycelium are privileged in penicillin G secretion. led us to the conclusion that the immunogold marker of isopenicillin N synthase is abundantly arranged at polyribosomes surrounding the peroxisomes. Such a cellular accumulation of isopenicillin N synthase may enhance the selective, continuous and sufficient sub strate supply in penicillin G biosynthesis. It was recently found that δ(Lαaminoadipyl)LcysteinylDvaline tripeptide is present in the cytoplasm and accumulates in the fermentation medium to concentrations of up to 2 mM (for review see Kurzątkowski et al., 2014a). The affinity of isopenicillin N synthase for this tripeptide is in the submM range. The high concentration of the tripeptide in the fermentation broth might explain our unexpected results concerning the localization of isopenicillin N synthase at the periphery of the cyto plasm and in channellike structures of the cell wall. This location might be a precisely adopted structural arrangement enabling the withdrawal of the tripeptide from the fermentation broth and from the cytoplasm for the peripherally located isopenicillin N synthase to increase the efficacy and yield in penicillin G bio synthesis. On the contrary, in the mature nongrowing hyphal cells of the low penicillinproducing strain P. chrysogenum Q176 the total lack of peroxisomes about 0.1 μm in diameter were visible.Peroxisomes play a crucial role in the production of penicillin G and cephalosporin C by industrial strains (Kurzątkowski and GębskaKuczerowska, 2015). High penicillin G producing strains show increasing num bers of large peroxisomes mainly at the period of the Fig. 1. P. chrysogenum PQ96, 72 h culture, highpenicillin producing strain, activity of penicillin G biosynthesis (U/ml): total yield at 72 h of cultivation -8300 (4.98 g/1000 ml), increase of yield between 48 h and 72 h of fermentation -4850. The results of our experiments exhibit that the abundant vacuolar pexophagy of large peroxisomes combined with vacuolar budding and the presence of numerous vacuolar vesicles which fuse with the plasma membrane are the most important structural features characterizing the nongrowing productive cells as well as the lateapical degenerating highly vacuolated cells of the tested industrial strain. This structural arrange ment is closely combined with the period of largescale secretion of penicillin G. Such a cellular organization was not visible...

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