A novel Candida albicans Als3, Hwp1 and Met6 derived complex peptide protects mice against hematogenously induced candidiasis.

Candida albicans can cause superficial or systemic infections in humans, particularly in immunocompromised individuals. Vaccination strategies targeting specific antigens of C. albicans have shown promise in providing protection against invasive candidiasis. This study aimed to evaluate the immuno-protective capacity of a KLH conjugated complex peptide, 3P-KLH, containing epitopes from C. albicans antigens Als3, Hwp1, and Met6 in a murine model of hematogenously induced candidiasis. Mice immunized with 3P-KLH raised a specific antibody response, and protection against C. albicans infection was assessed. Immunized mice exhibited significantly lower fungal load in their kidneys compared to the control group. Moreover, 37.5 % of immunized mice survived 21 days after the infection, while all control animals died within the first nine days. These findings suggest that the 3P-KLH complex peptide, targeting C. albicans key antigens, elicits a protective immune response and reduces the severity of systemic Candida infection. In addition, the high binding affinity of the selected epitopes with MHC II alleles further supports the potential immunogenicity of this peptide in humans. This research provides insights into the development of novel immunotherapeutic approaches against invasive candidiasis.

Coincidence of antibodies against Hwp1 and ASCA, two distinct molecular targets of Candida albicans, reinforces the link between this fungal species and coeliac disease.

Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibodies (ASCA), a serological marker of Crohn's disease. ASCA has also been reported in other autoimmune diseases, including coeliac disease (CeD). A strong antibody response against Hwp1, a protein associated with invasive hyphal form of C. albicans which presents peptide sequence homologies with gliadin, has also been described in CeD. This observation supports the hypothesis that C. albicans hyphal transition in C. albicans may trigger CeD onset through a mechanism of molecular/antigenic mimicry. In this study, we assessed whether the anti-C. albicans oligomannose and anti-Hwp1 protein responses may be linked despite their different pathophysiological significance. The measurement of ASCA levels in a cohort of patients involved in our previous Hwp1 study showed a significant correlation between the two biomarkers. This new observation further reinforces the link between C. albicans and CeD.

Hyphal-associated protein expression is crucial for Candida albicans-induced eicosanoid biosynthesis in immune cells.

Candida albicans causes opportunistic infections ranging from mucosal mycoses to life-threatening systemic infections in immunocompromised patients. During C. albicans infection, leukotrienes and prostaglandins are formed from arachidonic acid by 5-lipoxygenase (5-LOX) and cyclooxygenases, respectively to amplify inflammatory conditions, but also to initiate macrophage infiltration to achieve tissue homeostasis. Since less is known about the cellular mechanisms triggering such lipid mediator biosynthesis, we investigated the eicosanoid formation in monocyte-derived M1 and M2 macrophages, neutrophils and HEK293 cells transfected with 5-LOX and 5-LOX-activating protein (FLAP) in response to C. albicans yeast or hyphae. Leukotriene biosynthesis was exclusively induced by hyphae in neutrophils and macrophages, whereas prostaglandin E2 was also formed in response to yeast cells by M1 macrophages. Eicosanoid biosynthesis was significantly higher in M1 compared to M2 macrophages. In HEK_5-LOX/FLAP cells only hyphae activated the essential 5-LOX translocation to the nuclear membrane. Using yeast-locked C. albicans mutants, we demonstrated that hyphal-associated protein expression is critical in eicosanoid formation. For neutrophils and HEK_5-LOX/FLAP cells, hyphal wall protein 1 was identified as the essential surface protein that stimulates leukotriene biosynthesis. In summary, our data suggest that hyphal-associated proteins of C. albicans are central triggers of eicosanoid biosynthesis in human phagocytes.

Diagnosis of Oral candidiasis in Patients under 12 Years: 18S rRNA as a Marker of Molecular Characterization of Candida tropicalis.

Candida tropical has been found as the most abundant pathogenic yeast species under the group Candida-non-albicans. Despite this, it is taxonomically related to C. albicans and has many of its pathogenic characteristics. Infection with Candida tropicalis is closely associated with many virulence factors encoded by multiple virulence genes. This study aims to diagnose C. tropicalis based on the presence of 18SrRNA and to detect many virulence genes. C. tropicalis isolates were collected from oral candidiasis patients. Children infected with oral thrush ranging in age from infants to 12 years old provided 150 samples. C. albicans (66.68 %), C. tropicalis (13.21 %), C. krusie (9.43 %), C. parapsilosis (7.55 %), and C. glarata were isolated as C. tropicalis types, according to the findings of the present study (2.83%). The presence of the 18SrRNA gene was confirmed in the isolates. All isolates were positive for cph1 and hwp1, while some were positive for sap1 (78.5%) and plb1 genes (71.4%). Using sequences and phylogenetic trees, it was determined that there was negligible genetic variation between local isolates and global strains. These virulence factor genes play a crucial role in developing infections.

Candida albicans Adhesins Als1 and Hwp1 Modulate Interactions with Streptococcus mutans.

Candida albicans and Streptococcus mutans are known to synergistically interact with each other in the oral cavity. For example, glucosyltransferase B (GtfB), secreted by S. mutans, can bind to the C. albicans cell surface, promoting dual-species biofilm formation. However, the fungal factors mediating interactions with S. mutans are unknown. The C. albicans adhesins Als1, Als3, and Hwp1 are key players in C. albicans single-species biofilm formation, but their roles, if any, in interacting with S. mutans have not been assessed. Here, we investigated the roles of the C. albicans cell wall adhesins Als1, Als3, and Hwp1 on forming dual-species biofilms with S. mutans. We assessed the abilities of the C. albicans wild-type als1Δ/Δ, als3Δ/Δ, als1Δ/Δ/als3Δ/Δ, and hwp1Δ/Δ strains to form dual-species biofilms with S. mutans by measuring optical density, metabolic activity, cell enumeration, biomass, thickness, and architecture of the biofilms. We observed that the C. albicans wild-type strain formed enhanced dual-species biofilms in the presence of S. mutans in these different biofilm assays, confirming that C. albicans and S. mutans synergistically interact in the context of biofilms. Our results reveal that C. albicans Als1 and Hwp1 are major players in interacting with S. mutans, since dual-species biofilm formation was not enhanced when the als1Δ/Δ or hwp1Δ/Δ strains were cultured with S. mutans in dual-species biofilms. Als3, however, does not seem to play a clear role in interacting with S. mutans in dual-species biofilm formation. Overall, our data suggest that the C. albicans adhesins Als1 and Hwp1 function to modulate interactions with S. mutans and could be potential targets for future therapeutics.

Development and Use of a Monoclonal Antibody Specific for the Candida albicans Cell-Surface Protein Hwp1.

The Candida albicans cell-surface protein Hwp1 functions in adhesion to the host and in biofilm formation. A peptide from the Gln-Pro-rich adhesive domain of Hwp1 was used to raise monoclonal antibody (MAb) 2-E8. MAb 2-E8 specificity for Hwp1 was demonstrated using a hwp1/hwp1 C. albicans isolate and strains that expressed at least one HWP1 allele. Immunofluorescence and atomic force microscopy experiments using MAb 2-E8 confirmed C. albicans germ-tube-specific detection of the Hwp1 protein. MAb 2-E8 also immunolabeled the tips of some Candida dubliniensis germ tubes grown under conditions that maximized HWP1 expression. The phylogeny of HWP1 and closely related genes suggested that the Gln-Pro-rich adhesive domain was unique to C. albicans and C. dubliniensis focusing the utility of MAb 2-E8 on these species. This new reagent can be used to address unanswered questions about Hwp1 and its interactions with other proteins in the context of C. albicans biology and pathogenesis.

Effect of Cigarette and E-Cigarette Smoke Condensates on Candida albicans Biofilm Formation and Gene Expression.

Smoking triggers environmental changes in the oral cavity and increases the risk of mucosal infections caused by Candida albicans such as oral candidiasis. While cigarette smoke has a significant impact on C. albicans, how e-cigarettes affect this oral pathogen is less clear. Here, we investigated the effect of cigarette and e-cigarette smoke condensates (CSC and ECSC) on C. albicans growth, biofilm formation, and gene expression. Whereas pure nicotine (N) at the minimum inhibitory concentration (MIC, 4 mg/mL) prevented C. albicans growth, enhanced biofilm formation was observed at 0.1 mg/mL. In contrast, at this nicotine sub-MIC (0.1 mg/mL) concentration, CSC and ECSC had no significant effect on C. albicans biofilm formation. Additionally, N, CSC, and ECSC increased the expression of HWP1 and SAP2 genes. The ECSC group exhibited elevated expression levels of the EAP1 and ALS3 genes, compared to the nicotine-free ECSC (-) control. Moreover, our in vitro study illustrated that the antifungal drugs, fluconazole and amphotericin B, alleviated the effect of nicotine on C. albicans gene expression. Overall, the results of the study indicated nicotine from different sources may affect the pathogenic characteristics of C. albicans, including hyphal growth, biofilm formation, and particularly the expression of virulence-related genes.

Candida species isolated from clinical samples in a tertiary hospital in Honduras: Where is Candida auris?

Background and Purpose: Infections by emerging and multiresistant Candida species are becoming more frequent throughout the world. This study aimed to describe Candida species in different wards of a tertiary hospital in Honduras. Materials and Methods: The prevalence of species within the C. albicans complex was estimated using a molecular approach, and C. auris was investigated using a yeast pool-based DNA extraction method. In total, 328 yeast isolates were identified using phenotypic approaches. For the identification of species within the C. albicans complex, a molecular approach based on the size polymorphisms of the hpw1 gene was used. In addition, a technique was optimized based on DNA extraction in pools for the rapid identification of C. auris. Results: A total of 11 species of Candida were identified in the hospital wards. C. albicans showed the highest number of isolates (52.4%). Within the C. albicans complex, C. albicans sensu stricto was the most common, followed by C. dubliniensis. However, C. auris was not found. Conclusion: Reports on the distribution of Candida species in Honduras are limited; accordingly, the data from this study are of importance for a better understanding of their epidemiology. Moreover, a simple method was offered for the detection of C. auris that could help in its detection in low-resource settings.

Anticandidal Potential of Two Cyanobacteria-Synthesized Silver Nanoparticles: Effects on Growth, Cell Morphology, and Key Virulence Attributes of Candida albicans.

Candida albicans is an opportunistic human fungal pathogen responsible for 90-100% of mucosal and nosocomial infections worldwide. The emergence of drug-resistant strains has resulted in adverse consequences for human health, including numerous deaths. Consequently, there is an urgent need to identify and develop new antimicrobial drugs to counter these effects. Antimicrobial nanoagents have shown potent inhibitory activity against a number of pathogens through targeting their defense systems, such as biofilm formation. Here, we investigated the anticandidal activity of silver nanoparticles biosynthesized by the cyanobacterial strains Desertifilum sp. IPPAS B-1220 and Nostoc Bahar_M (D-SNPs and N-SNPs, respectively), along with that of silver nitrate (AgNO3), and examined the mechanisms underlying their lethal effects. For this, we performed agar well diffusion and enzyme activity assays (lactate dehydrogenase, adenosine triphosphatase, glutathione peroxidase, and catalase) and undertook morphological examinations using transmission electron microscopy. The effects of the three treatments on Hwp1 and CDR1 gene expression and protein patterns were assessed using qRT-PCR and SDS-PAGE assays, respectively. All of the three treatments inhibited C. albicans growth; disrupted membrane integrity, metabolic function, and antioxidant activity; induced ultrastructural changes in the cell envelope; and disrupted cytoplasmic and nuclear contents. Of the three agents, D-SNPs showed the greatest biocidal activity against C. albicans. Additionally, the D-SNP treatment significantly reduced the gene expression of Hwp1 and CDR1, suggestive of negative effects on biofilm formation ability and resistance potential of C. albicans, and promoted protein degradation. The mechanism involved in the biocidal effects of both D-SNPs and N-SNPs against C. albicans could be attributed to their ability to interfere with fungal cell structures and/or stimulate oxidative stress, enabling them to be used as a robust antimycotic agent.

The Discrepancy between Clove and Non-Clove Cigarette Smoke-Promoted Candida albicans Biofilm Formation with Precoating RNA-aptamer.

This study explores the influence of precoating aptamer (Ca-apt1) on C. albicans viability while the fungus was growing in the presence of exposing condensed cigarette smoke (CSC), prepared from clove (CCSC) and non-clove (NCSC) cigarettes, for 48 h. Using qPCR, we found that mRNA expression of adhesion-associated genes ( ALS3 and HWP1) was impaired by precoating C. albicans yeast cells with the aptamer. Conversely, the gene transcription was upregulated when aptamer-uncoated yeast was pre-treated with either CSC. In addition, by analysing the result of MTT ([3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay, we found that the presence of added CCSC or NCSC in growth medium for 48 h was significantly enhanced C. albicans biofilm development. However, the presence of precoated aptamer was significantly impaired biofilm development accelerated by the NCSC. The inhibitory effect of the Ca-apt1 was not dependent on the precoated aptamer (1 and 10%). Interestingly, we noted that the enhancer effect of treated CCSC was no longer effective when the yeast had been precoated with 10% aptamer tested. Additionally, light microscopy analysis revealed that precoating aptamer alleviates morphological changes of C. albicans (from yeast to hypha formation) that are enhanced by adding CCSC or NCSC in the growth medium. In conclusion, these results suggest that administration on Ca-ap1 exhibits a significant protective effect on CSC-induced biofilm formation by C. albicans.

Candida albicans Biofilm Inhibition by Two Vaccinium macrocarpon (Cranberry) Urinary Metabolites: 5-(3',4'-DihydroxyPhenyl)-γ-Valerolactone and 4-Hydroxybenzoic Acid.

Candida spp. are pathobionts, as they can switch from commensals to pathogens, responsible for a variety of pathological processes. Adhesion to surfaces, morphological switch and biofilm-forming ability are the recognized virulence factors promoting yeast virulence. Sessile lifestyle also favors fungal persistence and antifungal tolerance. In this study, we investigated, in vitro, the efficacy of two urinary cranberry metabolites, 5-(3',4'-dihydroxy phenyl)-γ-valerolactone (VAL) and 4-hydroxybenzoic acid (4-HBA), in inhibiting C. albicans adhesion and biofilm formation. Both the reference strain SC5314 and clinical isolates were used. We evaluated biomass reduction, by confocal microscopy and crystal violet assay, and the possible mechanisms mediating their inhibitory effects. Both VAL and 4-HBA were able to interfere with the yeast adhesion, by modulating the expression of key genes, HWP1 and ALS3. A significant dose-dependent reduction in biofilm biomass and metabolic activity was also recorded. Our data showed that the two cranberry metabolites VAL and 4-HBA could pave the way for drug development, for targeting the very early phases of biofilm formation and for preventing genitourinary Candida infections.

Biomarkers for the diagnosis of invasive candidiasis in immunocompetent and immunocompromised patients.

Blood culture methods show low sensitivity, so reliable non-culture diagnostic tests are needed to help clinicians with the introduction, de-escalation, and discontinuation of antifungal therapy in patients with suspected invasive candidiasis (IC). We evaluated different biomarkers for the diagnosis of IC in immunocompetent and immunocompromised patients at risk for developing invasive fungal diseases. The specificity of Candida albicans germ-tube antibodies (CAGTA) detection was high (89%-100%), but sensitivity did not exceed 61% even after raising the cut-off from 1/160 to 1/80. We developed enzyme-linked immunoassays detecting antibodies against C. albicans proteins (Als3-N, Hwp1-N, or Met6) that resulted more sensitive (66%-92%) but less specific than CAGTA assay. The combination of 1,3-beta-D-glucan (BDG) detection and CAGTA results provided the highest diagnostic usefulness in immunocompetent patients. However, in immunocompromised patients, anti-Met6 antibodies was the best biomarker, both, alone or in combination with BDG.

Molecular identification and antifungal susceptibility profiles of Candida dubliniensis and Candida africana isolated from vulvovaginal candidiasis: A single-centre experience in Iran.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common and debilitating long-term illness affecting million women worldwide. This disease is caused mainly by Candida albicans and a lesser extent by other species, including the two phylogenetically closely related pathogens Candida africana and Candida dubliniensis. OBJECTIVES: In this study, we report detailed molecular epidemiological data about the occurrence of these two pathogenic yeasts in Iranian patients affected by VVC, or its chronic recurrent form (RVVC), and provide, for the first time, data on the antifungal activity of two new drugs, efinaconazole (EFN) and luliconazole (LUL). METHODS: A total of 133 vaginal yeast isolates, presumptively identified as C albicans by phenotypic and restriction analysis of rDNA, were further analysed by using a specific molecular method targeting the HWP1 gene. All C africana and C dubliniensis isolates were also tested for their in vitro susceptibility to a panel of modern and classical antifungal drugs. RESULTS AND CONCLUSIONS: Based on the molecular results, among 133 germ-tube positive isolates, we identify 119 C albicans (89.47%), 11 C africana (8.27%) and 3 C dubliniensis (2.26%) isolates. C africana and C dubliniensis showed low MIC values for most of the antifungal drugs tested, especially for EFN and LUL, which exhibited a remarkable antifungal activity. High MIC values were observed only for nystatin and terbinafine. Although C albicans remains the most common Candida species recovered from Iranian VVC/RVVC patients, our data show that its prevalence may be slightly overestimated due to the presence of difficult-to-identify closely related yeast, especially C africana.

Differentiation of Candida albicans complex species isolated from invasive and non-invasive infections using HWP1 gene size polymorphism.

BACKGROUND AND PURPOSE: Taxonomy of Candida is controversial and has changed due to the investigation of the novel species. Candida africana and Candida dubliniensis are new members of the C. albicans complex that are currently gaining both clinical and epidemiologic significance. This study aimed to report the prevalence of C. africana among the strains isolated from patients using hyphal wall protein 1 (HWP1) gene size polymorphism. MATERIALS AND METHODS: In total, 235 yeasts confirmed as C. albicans complex based on chromogenic media and internal transcribed spacers sequencing isolated from various clinical forms of invasive and non-invasive candidiasis mainly candidemia were re-identified using HWP1 gene polymorphisms. The HWP1-polymerase chain reaction amplicons were re-confirmed by sequencing and BLAST analysis. RESULTS: Based on the HWP1 gene size polymorphism, 223 strains were identified as C. albicans (94.89%) from which 7 isolates produced two DNA fragments (850 and 941 bp). The C. dubliniensis (n=4, 1.7%), C. africana (n=1, 0.42%), and mix of C. albicans and C. africana (n=7, 2.97%) were also identified. CONCLUSION: It can be said that C. albicans remains the most common Candida species, while C. dubliniensis and C. africana are rarely found among the patient isolates. Due to limited information on the molecular epidemiology of this novel yeast, more studies using molecular methods are recommended.

Effect of Dermaseptin S4 on C. albicans Growth and EAP1 and HWP1 Gene Expression.

Increasing resistance and changes in the spectrum of Candida infections have generated considerable interest in the development of new antifungal molecules. The use of antimicrobial peptides (AMPs) appears to be a promising approach. Frog skin AMPs (such as dermaseptins) have shown antimicrobial activity against several pathogens. In this study, we aimed to test the antimicrobial efficacy of dermaseptin S4 (DS4) against C. albicans. We determined the minimal inhibitory concentration (MIC) of DS4, and investigated the effects of the DS4 at low concentrations on human primary gingival fibroblasts. Additionally, we evaluated the effect of DS4 on C. albicans growth, form changes, and biofilm formation, as well as the expression of certain virulent genes. Our data show that DS4 completely inhibits C. albicans growth at a concentration of 32 µg/mL referring to the MIC of DS4. It should be noted that even with low concentrations (below 16 µg/mL), DS4 still have significant growth reduction of C. albicans, but were not toxic to human gingival fibroblasts. DS4 inhibited the transition from yeast to hyphae, and decreased the biofilm formation by reducing the biofilm mass weight. Surface morphological changes in the yeast cell membrane were observed following exposure to DS4. The gene expression analyses revealed that DS4 significantly decreased the expression of EAP1 and HWP1 genes. Overall results suggest the potential use of DS4 as an antifungal therapy to prevent C. albicans pathogenesis.

Candida albicans in celiac disease: A wolf in sheep's clothing.

Candida albicans is a commensal fungus with a potential pathogenicity and celiac disease is an autoimmune condition. Both share multiple pathophysiological junctions, including serological markers against cell-wall proteins of Candida, anti-gliadin antibodies are positive in both entities, gluten and a candidal virulence factor share sequence similarity and the autoantigen of celiac disease, the tissue transglutaminase, is pivotal in Candida albicans commensalism and hostile behavior and its covalently cross linked products are stable and resistant to breakdown in the two entities. Those autoimmune/infectious cross roads are the basis for the hypothesis that Candida albicans is an additional environmental factor for celiac disease autoimmunogenesis.

Low prevalence of antifungal resistant Candida africana, in the C. albicans complex causing vulvovaginal candidiasis.

The Candida (C.) albicans complex includes C. albicans, C. dubliniensis, C. stellatoidea, and C. africana, with the last mentioned as an important emerging agent of vulvovaginal candidiasis (VVC). The aim of the study was to identify C. africana and C. dubliniensis and assess their drug susceptibility in vaginitis. One-hundred Candida isolates of the C. albicans complex from women diagnosed with vaginitis and from vaginal samples in the culture collection of a medical mycology laboratory were examined. Species of the C. albicans complex were identified with conventional and molecular methods using polymerase chain reaction (PCR) for amplification and sequencing of the internal transcribed spacer (ITS) region, PCR for partial amplification of hyphal wall protein 1 (HWP1) gene and duplex PCR. The effects of antifungal drugs were evaluated according to standard broth microdilution protocols. Ninety-seven C. albicans (97%) and three C. africana (3%) isolates were identified. Results of susceptibility testing revealed one isolate of C. africana to be resistant to both clotrimazole and fluconazole, and one showed reduced susceptibility to itraconazole. Identification of Candida species especially C. africana in vaginitis is crucial, there are varying levels of resistance to antifungal drugs.

Identification of Cryptic Species of Four Candida Complexes in a Culture Collection.

Candida spp. are one of the most common causes of fungal infections worldwide. The taxonomy of Candida is controversial and has undergone recent changes due to novel genetically related species. Therefore, some complexes of cryptic species have been proposed. In clinical settings, the correct identification of Candida species is relevant since some species are associated with high resistance to antifungal drugs and increased virulence. This study aimed to identify the species of four Candida complexes (C. albicans, C. glabrata, C. parapsilosis, and C. haemulonii) by molecular methods. This is the first report of six cryptic Candida species in Honduras: C. dubliniensis, C. africana, C. duobushaemulonii, C. orthopsilosis, and C. metapsilosis, and it is also the first report of the allele hwp1-2 of C. albicans sensu stricto. It was not possible to demonstrate the existence of C. auris among the isolates of the C. haemulonii complex. We also propose a simple method based on PCR-RFLP for the discrimination of the multi-resistant pathogen C. auris within the C. haemulonii complex.

Candida africana in recurrent vulvovaginal candidiasis (RVVC) patients: frequency and phenotypic and genotypic characteristics.

PURPOSE: Up to 75 % of all women develop vulvovaginal candidiasis (VVC), with symptoms such as vulvar erythema, pruritus and abnormal vaginal discharge. Despite the global distribution of Candida africana, its role in recurrent vulvovaginal candidiasis (RVVC) is still unclear and requires further investigation. Here, we report on the frequency of C. africana among clinical isolates from patients with RVVC in Bushehr in southern Iran. METHODOLOGY: Isolated Candida strains were identified by ITS-PCR-RFLP. Hyphal wall protein 1 (HWP1) was amplified to differentiate C. africana and the resulting sequences were subjected to phylogenetic analyses with a view to identifying similarities and differences in nucleotides. RESULTS: Ten out of 119 strains originally identified as C. albicans turned out to be C. africana. Pairwise nucleotide alignment of HWP1 DNA sequences showed 100 % similarity between C. africana strains. Inter-species variation between Iranian C. africana HWP1 sequences and the only three available C. africana type sequences in GenBank revealed 99.7-100 % nucleotide similarity. Phylogenetic analysis of the HWP1 DNA sequences of 10 Iranian C. africana isolates, the 3 C. africana sequences available in GenBank and 2 representative Iranian C. albicans sequences revealed that all 11 Iranian C. africana strains formed a well-supported cluster separated from the remaining C. africana. CONCLUSION: In our sample, C. africana was only isolated from 7.8 % of the patients with RVVC. While size polymorphisms in HPW1 genes allowed us to differentiate C. africana from C. albicans, no evidence of sequence variation within the Iranian C. africana isolates was observed.

Dermaseptin-S1 decreases Candida albicans growth, biofilm formation and the expression of hyphal wall protein 1 and aspartic protease genes.

AIMS: This study aimed to investigate the effect of synthetic antimicrobial peptide dermaseptin-S1 (DS1) (ALWKTMLKKLGTMALHAGKAALGAADTISQGTQ) on the growth of Candida albicans, its transition from blastospore to hyphae, and its biofilm formation. We also analysed the expression of different genes (HWP1 and SAPs) involved in C. albicans virulence. METHODS AND RESULTS: Using cell count we showed that in addition to decreasing C. albicans growth, peptide DS1 inhibited its transition from blastospore to hyphal form. These effects are comparable to those obtained with amphotericin B (AmB). Electron microscopy analyses showed that C. albicans cells treated with either DS1 or AmB displayed a distorted cell wall surface, suggesting that the effect of DS1 was similar to that of AmB on C. albicans cell membrane structure. These observations were confirmed by our results with biofilms showing that both DS1 peptide and AmB significantly inhibited biofilm formation after 2 and 4 days. The effect of DS1 on C. albicans growth, transition and biofilm formation may occur through gene modulation, as the expression of HWP1, SAP1, SAP2, SAP3, SAP9 and SAP10 genes involved in C. albicans pathogenesis were all downregulated when C. albicans was treated with DS1. CONCLUSIONS: DS1 inhibits the growth and hyphal transition of C. albicans. DS1 was also able to decrease the expression of and gene expression of hyphal wall protein 1 and aspartic proteases genes by C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide new insight into the efficacy of DS1 against C. albicans and its potential for use as an antifungal therapy.