Photoactivated riboflavin inhibits planktonic and biofilm growth of Candida albicans and non-albicans Candida species.

Fungal infections caused by Candida species pose a serious threat to humankind. Antibiotics abuse and the ability of Candida species to form biofilm have escalated the emergence of drug resistance in clinical settings and hence, rendered it more difficult to treat Candida-related diseases. Lethal effects of Candida infection are often due to inefficacy of antimicrobial treatments and failure of host immune response to clear infections. Previous studies have shown that a combination of riboflavin with UVA (riboflavin/UVA) light demonstrate candidacidal activity albeit its mechanism of actions remain elusive. Thus, this study sought to investigate antifungal and antibiofilm properties by combining riboflavin with UVA against Candida albicans and non-albicans Candida species. The MIC20 for the fluconazole and riboflavin/UVA against the Candida species tested was within the range of 0.125-2 µg/mL while the SMIC50 was 32 µg/mL. Present findings indicate that the inhibitory activities exerted by riboflavin/UVA towards planktonic cells are slightly less effective as compared to controls. However, the efficacy of the combination towards Candida species biofilms showed otherwise. Inhibitory effects exerted by riboflavin/UVA towards most of the tested Candida species biofilms points towards a variation in mode of action that could make it an ideal alternative therapeutic for biofilm-related infections.

Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list.

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters. Candida parapsilosis is one of the pathogens considered in the WHO priority pathogens list, and this review was conducted to inform the ranking of the pathogen in the list. In this systematic review, we searched PubMed and Web of Science to find studies between 2011 and 2021 reporting on the following criteria for C. parapsilosis infections: mortality, morbidity (hospitalisation and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. We identified 336 potentially relevant papers, of which 51 were included in the analyses. The included studies confirmed high mortality rates, ranging from 17.5% to 46.8%. Data on disability and sequelae were sparse. Many reports highlighted concerns with azole resistance, with resistance rates of >10% described in some regions. Annual incidence rates were relatively poorly described, although there was clear evidence that the proportion of candidaemia cases caused by C. parapsilosis increased over time. While this review summarises current data on C.parapsilosis, there remains an urgent need for ongoing research and surveillance to fully understand and manage this increasingly important pathogen.

The first prevalence and antifungal susceptibility profile of Candida infections in Palestine, 2022.

BACKGROUND: Candida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive. METHODS: We performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system. RESULTS: Our results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments. CONCLUSIONS: Four pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures' effectiveness.

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species.

Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

Yeasts originating from fermented foods, their potential as probiotics and therapeutic implication for human health and disease.

Yeasts derived from fermented foods have historically been known for their organoleptic properties, enriching nutritional values, and producing bioactive metabolites with therapeutic potential. In this review, we discuss the yeast flora in fermented foods, their functional aspects in fermentation, as well as their probiotic and biotherapeutic properties. These yeasts have numerous physical and biochemical characteristics, such as larger cells as compared to bacteria, a rigid cell wall composed primarily of glucans and mannans, natural resistance to antibiotics, and the secretion of secondary metabolites that are both pleasing to the consumer and beneficial to the host's health and well-being. The review also focused on therapeutic applications of probiotic yeasts derived from fermented foods on infections associated with Candida species. These potential probiotic yeasts present an additional avenue to treat dysbiosis of the gut microbiota and prevent health complications that arise from opportunistic fungal colonization, especially drug-resistant superbugs, which are highlighted in this review.

Prevalence and species distribution of Candida bloodstream infection in children and adults in two teaching university hospitals in Egypt: first report of Candida kefyr.

BACKGROUND: Candidemia is a pervasive problem associated with significant morbidity and mortality in health care settings. This study aimed to determine the changing distribution of Candida species and the emergence of uncommon species. METHODS: This was a cross-sectional study performed in two Cairo University hospitals between 2019 and 2020. All Candida species isolates recovered from blood cultures of adults and pediatrics patients admitted to the hospitals were included. Candida isolates were identified by chromogenic Candida agar and Vitek2 YST identification card. Candida kefyr was confirmed by chip array. RESULTS: Candida species were responsible for 1.6% of bloodstream infections in adults and 10.8% in pediatric patients. C. albicans was the most prevalent species representing 27.8% in adults and 48.3% in pediatrics. Non-albicans species (NAC) represented the most isolated Candida species among adults and pediatrics (72.2% and 51.6%, respectively) with the predominance of C. tropicalis (27.8% and 22.5%, respectively) followed by C. parapsilosis (16.7% and 10.8%, respectively). The uncommon Candida, which is Candida species other than C. albicans, C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei, represents 16.6% and 14% of all candidemia in adults and pediatrics, respectively. Only one of each of C. lusitaniae, C. utilis, and C. kefyr were detected in adults. C. lusitaniae was the most frequently recovered uncommon Candida among pediatrics resulting in 6.4% of candidemia followed by C. famata (4.3%), C. utilis (2.2%), and C. kefyr (1.1%). CONCLUSIONS: C. albicans is still the primary species isolated from pediatrics and adults with candidemia despite the considerable shift to the non-albicans species. C. tropicalis and C. parapsilosis are the most prevalent NAC. The increased prevalence of uncommon Candida species is alarming and necessitates a prompt stewardship program.

Evaluation of candidemia in children at a university hospital: A retrospective cohort.

BACKGROUND: Candidemia is a life-threatening infection in hospitalied children. This study aimed to evaluate candidemia's demographic and clinical characteristics and identify the risk factors and outcomes of Candida albicans (CA) and non-albicans Candida (NAC) spp. METHODS: A retrospective cohort was designed to evaluate paediatric patients with candidemia between January 2008 and December 2020. RESULTS: A total of 342 episodes in 311 patients were evaluated. The median age of the patients was 2.1 years (1 month-17 years and 6 months), and 59.6% were male. The prevalence of NAC (67.5%) candidemia was higher than that of CA (32.5%). The most commonly isolated Candida species was Candida parapsilosis (43.3%), followed by C. albicans (32.5%), Candida glabrata (6.1%) and Candida tropicalis (5.0%). The length of hospital stay prior to the positive culture and the total length of hospital stay were longer in the NAC group (p = .003 and p = .006). The neutrophil count was lower in the NAC group (p = .007). In the multivariate analysis, total parenteral nutrition, antifungal prophylaxis and a history of coagulase-negative staphylococci (CoNS) culture positivity in the past month were risk factors for developing candidemia due to NAC (p values were .003, .003 and .045). C. albicans and C. parapsilosis fluconazole resistance were 9.5% and 46.6%, respectively. The rates of amphotericin B resistance were 1.1% and 7.6% in C. albicans and C. parapsilosis, respectively. Mortality (14-day and 30-day) rates did not differ between the groups. CONCLUSIONS: A history of CoNS culture positivity in the past month, total parenteral nutrition, and antifungal prophylaxis increases the risk of NAC candidemia.

Effect of coccidioidomycosis prophylaxis in selecting non-Candida albicans species amongst solid organ transplant recipients in Arizona.

BACKGROUND: Invasive candidiasis carries an increased risk of morbidity and mortality. The rates of non-albicans Candida species (NAC) infections are on the rise secondary to frequent azole antifungal use. NAC incidence and risk amongst solid organ transplant (SOT) recipients in Arizona receiving prolonged azole course for coccidioidomycosis prophylaxis have not been well elucidated. METHODS: We retrospectively evaluated SOT recipients hospitalised between 2017 and 2021 with a positive Candida spp. culture. RESULTS: There were 66 SOT recipients with 74 hospitalisations and 79 Candida spp. isolates. The median age was 59 (IQR 45-66), 68% were male, 58% were non-Hispanic White, and the most common SOT 38/74 (51%) was a liver transplant. Median time from transplant to the identification of any NAC (infection or colonisation) was significantly shorter, 8 months (IQR 3-78) vs 128 months (IQR 10-282) for Candida albicans isolates, p = .03. Prior use of azoles was significantly higher in NAC-associated post-transplant colonisation and invasive disease hospitalisations (83%) than in those with C. albicans (17%), p < .001. There were 59 hospitalisations with invasive disease, with the majority having NAC isolates of 49 (83%). CONCLUSION: The universal azole prophylaxis has reduced the incidence of coccidioidomycosis complications amongst SOT recipients in Arizona; however, there is an increased risk of developing NAC colonisation and infections, which can complicate the care of the SOT recipients with invasive candidiasis. Future studies are needed to investigate methods of reducing the risk of NAC infections whilst preventing coccidioidomycosis amongst SOT recipients.

Epidemiology of Invasive Candidiasis in Patients with Hematologic Malignancy on Antifungal Prophylaxis.

The landscape of invasive Candida infections in patients with hematologic malignancy has evolved due to the adoption of anti-fungal prophylaxis, advances in oncological therapies, and developments in antifungal therapies and diagnostics. Despite these scientific gains, the morbidity and mortality caused by these infections remain unchanged, highlighting the importance of an updated understanding of its epidemiology. Non-albicans Candida species are now the predominant cause of invasive candidiasis in patients with hematological malignancy. This epidemiological shift from Candida albicans to non-albicans Candida species is partially a consequence of selective pressure from extensive azole use. Further analysis of this trend suggests other contributing factors including immunocompromise caused by the underlying hematologic malignancy and the intensity of its associated treatments, oncological practices, and regional or institution specific variables. This review characterizes the changing distribution of Candida species in patients with hematologic malignancy, describes the causes driving this change, and discusses clinical considerations to optimize management in this high-risk patient population.

Multilocus sequence typing (MLST) analysis reveals many novel genotypes and a high level of genetic diversity in Candida tropicalis isolates from Italy and Africa.

BACKGROUND: Candida tropicalis is a human pathogenic yeast frequently isolated in Latin America and Asian-Pacific regions, although recent studies showed that it is also becoming increasingly widespread throughout several African and south-European countries. Nevertheless, relatively little is known about its global patterns of genetic variation as most of existing multilocus sequence typing (MLST) data come from Asia and there are no genotyped African isolates. OBJECTIVES: We report detailed genotyping data from a large set of C. tropicalis isolates recovered from different clinical sources in Italy, Egypt and Cameroon in order to expand the allele/genotype library of MLST database (https://pubmlst.org/ctropicalis), and to explore the genetic diversity in this species. METHODS: A total of 103 C. tropicalis isolates were genotyped using the MLST scheme developed for this species. All isolates were also tested for in vitro susceptibility to various antifungals to assess whether certain genotypes were associated with drug-resistance. RESULTS AND CONCLUSIONS: A total of 104 different alleles were detected across the MLST-loci investigated. The allelic diversity found at these loci resulted in 51 unique MLST genotypes of which 36 (70.6%) were novel. Global optimal eBURST analysis identified 18 clonal complexes (CCs) and confirm the existence of a specific Italian-cluster (CC36). Three CCs were also statistically associated with fluconazole resistance, which was elevated in Cameroon and Egypt. Our data show high genetic diversity in our isolates suggesting that the global population structure of C. tropicalis is still poorly understood. Moreover, its clinical impact in Italy, Egypt and Cameroon appears to be relevant and should be carefully considered.

Rationalisation of Antifungal Properties of α-Helical Pore-Forming Peptide, Mastoparan B.

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.

Candida albicans and Candida glabrata triosephosphate isomerase - a moonlighting protein that can be exposed on the candidal cell surface and bind to human extracellular matrix proteins.

BACKGROUND: Triosephosphate isomerase (Tpi1) is a glycolytic enzyme that has recently been reported also to be an atypical proteinaceous component of the Candida yeast cell wall. Similar to other known candidal "moonlighting proteins", surface-exposed Tpi1 is likely to contribute to fungal adhesion during the colonization and infection of a human host. The aim of our present study was to directly prove the presence of Tpi1 on C. albicans and C. glabrata cells under various growth conditions and characterize the interactions of native Tpi1, isolated and purified from the candidal cell wall, with human extracellular matrix proteins. RESULTS: Surface plasmon resonance measurements were used to determine the dissociation constants for the complexes of Tpi1 with host proteins and these values were found to fall within a relatively narrow range of 10- 8-10- 7 M. Using a chemical cross-linking method, two motifs of the Tpi1 molecule (aa 4-17 and aa 224-247) were identified to be directly involved in the interaction with vitronectin. A proposed structural model for Tpi1 confirmed that these interaction sites were at a considerable distance from the catalytic active site. Synthetic peptides with these sequences significantly inhibited Tpi1 binding to several extracellular matrix proteins suggesting that a common region on the surface of Tpi1 molecule is involved in the interactions with the host proteins. CONCLUSIONS: The current study provided structural insights into the interactions of human extracellular matrix proteins with Tpi1 that can occur at the cell surface of Candida yeasts and contribute to the host infection by these fungal pathogens.

Candida prevalence in saliva before and after oral cancer treatment.

BACKGROUND: Previous studies have shown an increased prevalence of candidiasis in patients receiving radiotherapy for head and neck cancer. However, little is known of the effect the different cancer treatment modalities have on the oral Candida status. OBJECTIVE AND HYPOTHESIS: The objective of this study was to investigate the change in salivary Candida status of oral squamous cell carcinoma (OSCC) patients undergoing cancer treatment. The hypothesis was that cancer treatments change the oral microbial environment favouring an increase in the prevalence of more pathogenic non-albicans Candida (NAC). METHODS: We collected paraffin-stimulated saliva from 44 OSCC patients before surgery and after a minimum of 19 months of follow-up. Chromagar, Bichro-Dupli-test and API ID 32 C were used for identification of different Candida species and results were analysed statistically. RESULTS: At both timepoints, 75% of samples were Candida positive with C. albicans being the most common yeast. NAC strains were present in 16% of the pre-operative samples and 14% of the follow-up samples. The NAC species found were C. dubliniensis, C. krusei, C. guilliermondii (preoperatively only) and C. glabrata (at follow-up only). In 73% of the cases, the salivary Candida status remained unchanged. There was an 18% increase in the prevalence of candidiasis. However, the different treatment modalities did not statistically significantly affect the Candida status of the patients. CONCLUSION: The intraindividual prevalence of salivary Candida among OSCC patients seems to be stable and different treatment modalities have little to no effect on the salivary Candida status.

The Inhibition of Non-albicans Candida Species and Uncommon Yeast Pathogens by Selected Essential Oils and Their Major Compounds.

The epidemiology of yeast infections and resistance to available antifungal drugs are rapidly increasing, and non-albicans Candida species and rare yeast species are increasingly emerging as major opportunistic pathogens. In order to identify new strategies to counter the threat of antimicrobial resistant microorganisms, essential oils (EOs) have become an important potential in the treatment of fungal infections. EOs and their bioactive pure compounds have been found to exhibit a wide range of remarkable biological activities. We investigated the in vitro antifungal activity of nine commercial EOs such as Thymus vulgaris (thyme red), Origanum vulgare (oregano), Lavandula vera (lavender), Pinus sylvestris (pine), Foeniculum vulgare (fennel), Melissa officinalis (lemon balm), Salvia officinalis (sage), Eugenia caryophyllata (clove) and Pelargonium asperum (geranium), and some of their main components (α-pinene, carvacrol, citronellal, eugenol, γ-terpinene, linalool, linalylacetate, terpinen-4-ol, thymol) against non-albicans Candida strains and uncommon yeasts. The EOs were analyzed by GC-MS, and their antifungal properties were evaluated by minimum inhibitory concentration and minimum fungicidal concentration parameters, in accordance with CLSI guidelines, with some modifications for EOs. Pine exhibited strong antifungal activity against the selected non-albicans Candida isolates and uncommon yeasts. In addition, lemon balm EOs and α-pinene exhibited strong antifungal activity against the selected non-albicans Candida yeasts. Thymol inhibited the growth of all uncommon yeasts. These data showed a promising potential application of EOs as natural adjuvant for management of infections by emerging non-albicans Candida species and uncommon pathogenic yeasts.

Assaying the effect of yeasts on growth of fungi associated with disease.

BACKGROUND: Pathogenic fungi often cause serious infections mainly in immunocompromised persons. The number of infections caused by the non-albicans Candida or other species has significantly increased over the last years. These infections present a major challenge in the health sector because these pathogenic fungi have strong virulence and often show resistance to the commonly used antifungal treatments. To solve the problems caused by the drug resistant pathogenic fungi, it is necessary to find new antifungal agents and their sources. The aim of this study was to give evidence that yeasts can effectively fight against strains which belong to pathogenic fungi and reveal those yeasts which are able to inhibit growth of Kodamaea ohmeri, Pichia kudriavzevii, Naganishia albida or Candida tropicalis. Furthermore, we wanted to determine the effects of certain culturing factors on the growth inhibition. RESULTS: Our screening revealed that although the strains belonging to pathogenic species were much more tolerant to the yeast-produced bioactive agents than the non-disease-associated yeasts, growth of Kodamaea ohmeri and Candida tropicalis could be inhibited by Metschnikowia andauensis, while Naganishia albida could be controlled by Pichia anomala or Candida tropicalis. Our data proved that the experimental circumstances could have a serious impact on the inhibitory capacity of the yeasts. Appearance of inhibition strongly depended on media, pH and temperature. Our data also shed some light on the fact that Pichia kudriavzevii must have high natural resistance to the yeast-produced agents, while other species, such as Saccharomycopsis crataegensis belonged to the easily inhibitable species. CONCLUSIONS: Our study suggests that yeast-produced bioactive agents could be potential growth inhibitory agents against the disease-associated fungi and yeasts can also contribute to alternative approaches to combat against pathogenic fungi. Our data revealed an important role of the culturing factors in inhibition and pointed to the complex nature of antagonism.

Distribution of Candida albicans and non-albicans Candida species isolated in different clinical samples and their in vitro antifungal suscetibity profile in Ethiopia.

BACKGROUND: The spectrum of yeasts and their antifungal susceptibility profile are poorly known and treatment of fungal disease has remained empirical. The aim of this study is to determine the spectrum and antifungal susceptibility profile of yeasts particularly of Candida species. METHODS: A descriptive study on the composition of Candida species and antifungal susceptibility profile were conducted from January 2018 to September 2018. Clinical samples collected from different sites were cultured on Sabouraud dextrose agar and incubated for an appropriate time. Identification of yeast isolates and their antifungal susceptibility profile were determined by the VITEK 2 compact system. Descriptive statistics such as frequency and percentage of Candida species were calculated using SPSS version 20. RESULTS: Of 209 yeasts recovered, 104(49.8%), 90 (43.1%), 15(7.2%) were C. albicans, non albicans Candida species, and other yeasts, respectively. Among non albicans Candida species, Candida krusei was the commonest isolate. Of other yeast groups, 66.7% was represented by Cryptococcus laurentii. Regardless of Candida species identified, 85.6, 3.9, and 10.5% of the isolates were susceptible, intermediate, and resistant to fluconazole, respectively. C krusei was 100% resistant to the drug. Voriconazole demonstrated the greatest antifungal activity against Candida isolates in which 99.4% of Candida isolates were susceptible. The susceptibility and the resistance rate of Candida isolate to both caspofungin and micafungin were the same being 96 and 4% respectively. However, micafungin was more potent than caspofungin. The susceptibility, resistant, and intermediate rates of yeasts against flucytosine were, 86.2, 6.6, and 7.2%, respectively. CONCLUSIONS: The present study demonstrated the distribution of Candida species in different clinical specimens where the isolation rate of non-albicans Candida species was comparable to Candida albicans. The high resistance rate of C. krusei to fluconazole and flucytosine may demonstrate that the treatment of candidiasis empirically is questionable.

Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review.

Recurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and different Trichomonas vaginalis strains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale for Lactobacilli dominance and changes that occur in healthy VMB throughout a women's life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. "VMB dominated with Lactobacilli is healthier than a diverse VMB". These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women's response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.

Prevalence of vulvovaginal candidiasis among pregnant women in the Ho municipality, Ghana: species identification and antifungal susceptibility of Candida isolates.

BACKGROUND: Candida is the leading cause of vaginitis, and 75% of women have at least one episode of infection in their lives, with pregnancy being a predisposing factor. If left untreated, vulvovaginal candidiasis (VVC) can lead to chorioamnionitis with subsequent abortion, prematurity and congenital infection of the neonate. We aimed to determine the prevalence of VVC, identify the recent and most frequently occurring species of Candida in pregnant women, and determine the most effective antifungal drug of choice for treatment. METHOD: A prospective cross-sectional study in which 176 high vaginal swab samples of consented pregnant women visiting the antenatal clinic from February 2018 to April 2018 were subjected to direct gram smear and culture for Candida isolation. Candida isolates were identified using a germ tube test and HiCrome Candida differential agar. Candida isolates were then subjected to a disk diffusion method using fluconazole (25 µg), nystatin (100 units), and voriconazole (1 µg) on Mueller-Hinton agar supplemented with 2% (w/v) glucose and 0.5 µg/ml methylene blue dye to determine the susceptibility pattern as per the guidelines of the Clinical Laboratory Standard Institute (CLSI). Chi-square analysis was used to ascertain the significant association of participants' sociodemographics and clinical presentations to VVC. A univariate logistic regression model was used to identify potential risk factors of VVC. RESULTS: The prevalence of VVC among our study participants was 30.7%. Non-albicans Candida (NAC) and Candida albicans had a prevalence of 74.1 and 25.9%, respectively. Candida glabrata was the most common species, followed by Candida albicans, Candida krusei, and Candida parapsilosis. 50.0, 18.5 and 3.7% of Candida species were susceptible to voriconazole, fluconazole and nystatin, respectively, whereas 37.0, 48.1 and 9.3% of Candida species were resistant to voriconazole, fluconazole and nystatin, respectively. The majority of isolates were susceptible dose dependent to all three antifungal agents, with voriconazole being the most efficacious antifungal agent. There was no significant association between participants' socio-demographic information and clinical presentations to VVC. CONCLUSION: The prevalence of VVC was high in the study area. C. glabrata was found to be the most common cause of VVC among the pregnant women attending antenatal clinics, in the Ho Municipality region of Ghana. The majority of the Candida isolates were susceptible and resistant to voriconazole and fluconazole, respectively.

Candida spp bloodstream infections in a Latin American Pediatric Oncology Reference Center: Epidemiology and associated factors.

BACKGROUND: Invasive fungal disease is a significant cause of morbidity and mortality in immunosuppressed children. The recognition of patients at risk for candidaemia is paramount to a better prognosis. OBJECTIVES: To characterize Candida spp bloodstream infections (BSI) in a reference centre for paediatric oncology and to describe the most prevalent risk factors associated with candida infections. PATIENTS/METHODS: This is a retrospective cohort study carried out with paediatric patients followed up with at the Institute of Pediatric Oncology, Brazil, who presented positive blood culture for Candida spp from January 2004 to December 2016. RESULTS: Ninety episodes of candidaemia were analysed; patients had a median age of 4.5 years, and 57.8% were males, with a diagnosis of solid tumours in 54.5% of cases. The most common Candida species were C albicans (35.6%), C parapsilosis (30.0%) and C tropicalis (16.7%). C tropicalis BSI was associated with neutropenia and skin lesions. Therapy was successful in 67.1% of the episodes. Older age and thrombocytopenia were associated with therapeutic failure. Death within 30 days occurred in 24.4% of patients; predictive factors were older age and admission to an ICU C parapsilosis candidaemia was a protective factor for death when compared to C albicans. CONCLUSION: The main species isolated were C albicans, C parapsilosis and C tropicalis. C tropicalis BSI was associated with neutropenia and skin lesions. The death rate was significant, and a worse prognosis was associated with older age, thrombocytopenia and admission to an ICU C parapsilosis infection proved to be a protective factor against mortality.

Structural Insights into the Interactions of Candidal Enolase with Human Vitronectin, Fibronectin and Plasminogen.

Significant amounts of enolase-a cytosolic enzyme involved in the glycolysis pathway-are exposed on the cell surface of Candida yeast. It has been hypothesized that this exposed enolase form contributes to infection-related phenomena such as fungal adhesion to human tissues, and the activation of fibrinolysis and extracellular matrix degradation. The aim of the present study was to characterize, in structural terms, the protein-protein interactions underlying these moonlighting functions of enolase. The tight binding of human vitronectin, fibronectin and plasminogen by purified C. albicans and C. tropicalis enolases was quantitatively analyzed by surface plasmon resonance measurements, and the dissociation constants of the formed complexes were determined to be in the 10-7-10-8 M range. In contrast, the binding of human proteins by the S.cerevisiae enzyme was much weaker. The chemical cross-linking method was used to map the sites on enolase molecules that come into direct contact with human proteins. An internal motif 235DKAGYKGKVGIAMDVASSEFYKDGK259 in C. albicans enolase was suggested to contribute to the binding of all three human proteins tested. Models for these interactions were developed and revealed the sites on the enolase molecule that bind human proteins, extensively overlap for these ligands, and are well-separated from the catalytic activity center.