Search Results (32)

Introduction: A group of approximately 15 Candida species are frequently found to be responsible for human invasive candidiasis, an infection that appears in patients with prolonged hospitalization, particularly in Intensive Care Units, and in immunosuppressed individuals. Given the considerable burden if not rapidly treated, clinicians face diagnostic challenges in distinguishing infection. The objective of this narrative review is to summarize the clinically applicable biomarkers used for invasive candidiasis and to evaluate their performance and create a diagnostic algorithm for clinical practice. Methods: This narrative review was conducted by searching PubMed and Scopus for studies published between 1990 and 2025, using keywords related to invasive candidiasis and non-culture diagnostic biomarkers. Clinical guidelines and consensus documents from major infectious diseases societies were additionally reviewed to supplement. Results: Blood cultures, which are considered the “gold standard” for diagnosis, face important fallouts caused by the limited sensitivity of 50%. Polymerase Chain Reaction assays can identify Candida species at an early stage when compared to blood cultures, demonstrating high specificity that ranges between 91% and 98, due to their high cost, and the limitations regarding only the identification of certain species, their widespread use remains limited. Non-culture serological tests such as mannan, anti-mannan and 1-3-β-D-glucan can detect fungal cell wall components or antibodies directed towards them. These tests have the advantage of being performed directly from blood samples. Reported sensitivity and specificity are 83% and 86% for mannan/anti-mannan, and 73% and 80% for 1-3-β-D-glucan, respectively. They are used for early detection of candidemia in high-risk patients, including immunocompromised individuals. Conclusions: Our report suggests that the traditional “gold standard” for diagnosing invasive candidiasis can be improved by integrating and combining novel biomarkers in the diagnostic pathways, and, thus, potentially reducing the time spent for diagnosing and facilitating early treatment access. Full article

The Candida species cell wall plays a pivotal role as a structural and functional barrier against external aggressors and as an intermediary in host–pathogen interactions. Candida species exhibit unique adaptations in their cell wall composition, with varying proportions of chitin, mannans, and β-glucans influenced by the environmental conditions and the morphological states. These components not only maintain cellular viability under osmotic, thermal, and chemical stress, but also serve as the key targets for novel antifungal strategies. MAPK signaling pathways, like the cell wall integrity pathway and the high-osmolarity glycerol pathway, play a crucial role in responding to cell wall stressors. Due to the rise of antifungal resistance and its clinical challenges, there is a need to identify new antifungal targets. This review discusses the recent advances in understanding the mechanisms underlying cell wall integrity, their impact on antifungal resistance and virulence, and their potential as therapeutic targets of C. albicans, N. glabratus, and C. auris. Full article

Candida auris, an emerging multidrug-resistant fungal pathogen, poses significant challenges in healthcare settings due to its high misidentification rate and resilience to treatments. Despite advancements in diagnostic tools, a gap remains in rapid, cost-effective identification methods that can differentiate C. auris from other Candida species, particularly on non-standard culture media. We used Raman spectroscopy to characterize C. auris grown on modified Dixon’s agar (mDixon) and differentiated it from Candida albicans and Candida parapsilosis. Key Raman spectral markers at 1171 cm⁻¹ and 1452 cm⁻¹, linked to mannan and β-glucan composition, differentiated C. auris into two subgroups, A and B. Despite the spectral similarities of groups A and B with C. albicans and C. parapsilosis, respectively, all Candida species were distinguishable through principal component analysis (PCA). Additionally, this study is the first to demonstrate the distinct spectral signature of mDixon agar, achieved through spatially offset Raman spectroscopy (SORS), which enables accurate discrimination between the culture medium and fungal samples. The observed inter-individual variability within C. auris, coupled with the spectral overlap between C. auris subgroups and other Candida species, highlights a major challenge in differentiating closely related fungi due to their similar molecular composition. Enhancements in spectral resolution and further fluorescence minimization from the culture medium are needed to reliably detect the subtle biochemical differences within these species. Despite these challenges, the results underscore the potential of Raman spectroscopy as a real-time, non-destructive, and complementary tool for fungal pathogen identification. Full article

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance, and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species. Full article

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though Candida albicans is the main causative agent, other Candida species, such as Candida tropicalis, are relevant etiological agents of candidiasis and candidemia. Compared with C. albicans, there is currently limited information about C. tropicalis’ biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains O-linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where O-linked mannans and other wall components are affected. Here, we generated a C. tropicalis pmt2∆ null mutant, which was affected in the first step of the O-linked mannosylation pathway. The null mutant was viable, contrasting with C. albicans where this gene is essential. The phenotypical characterization showed that O-linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in Galleria mellonella larvae. Thus, O-linked mannans are minor components of the cell wall that are involved in different aspects of C. tropicalis’ biology. Full article

Lactic acid bacteria can synthesize extracellular exopolysaccharides (EPSs) that have versatile physicochemical and biological properties. In this paper, the EPSs synthesized by Lacticaseibacillus rhamnosus ŁOCK 0943 were characterized. Their structure, biological, and technological activity, as well as application potential, were analyzed. Chemical analysis showed that this strain produces mannan and β-1,6-glucan. Their emulsifying, antagonistic, and antioxidant properties, along with their prebiotic potential, were assessed. The analysis of the tested polymers’ ability to create a stable emulsion showed that their emulsifying activity depends mainly on the type of oily substance used. The analysis of the antagonistic activity revealed that these EPSs can inhibit the growth of yeasts (e.g., Candida albicans ATCC 10231) and potentially pathogenic bacteria (e.g., Clostridium acetobutylicum ŁOCK 0831, Enterococcus faecalis ATCC 29212). Moreover, EPSs positively influenced the growth of all tested probiotic bacteria. Furthermore, EPSs can be successfully used as a preservative in cosmetic products. The most effective results were obtained with the use of a 0.05% solution of a chemical preservative (bronopol) and 0.25 mg/mL of the EPSs. Full article

Invasive candidiasis, including bloodstream infection (candidemia), encompasses the most severe forms of Candida infection. Several species-specific and non-specific serological assays are commercially available to aid in diagnosis. This study compared the performance of five such biomarker assays. Serum samples from 14 patients with proven or probable invasive candidiasis, and from 10 control patients, were included in the analysis. A total of 50 serum samples were tested using C. albicans germ tube antibody (CAGTA) assay (Vircell), C. albicans IgM, C. albicans IgG and Candida mannan assays (Dynamiker Biotechnology). Among these samples, the β-1-3-D-glucan (BDG) assay (Fungitell), a laboratory standard for the diagnosis of invasive candidiasis, was positive in 20 (40%), intermediate in five (10%) and negative in 25 (50%). In cases of proven or probable candidemia, the sensitivity and specificity of the BDG assay was 86% and 80%, respectively; the Candida mannan assay, 14% and 86%; the CAGTA test, 57% and 60%; the C. albicans IgM assay, 71% and 60%; and C. albicans IgG assay 29% and 90%. In 4/8 (50%) cases with multiple serum samples, C. albicans IgM was positive sooner than BDG. Thus, when used as a rule-out test for invasive candidiasis, our data suggest that the C. albicans IgM assay may assist antifungal stewardship (over serum BDG). Full article

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915–1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value. Full article

Candida albicans is an opportunistic fungal pathogen that may cause invasive infections in immunocompromised patients, disseminating through the bloodstream to other organs. In the heart, the initial step prior to invasion is the adhesion of the fungus to endothelial cells. Being the fungal cell wall’s outermost structure and the first to come in contact with host cells, it greatly modulates the interplay that later will derive in the colonization of the host tissue. In this work, we studied the functional contribution of N-linked and O-linked mannans of the cell wall of C. albicans to the interaction with the coronary endothelium. An isolated rat heart model was used to assess cardiac parameters related to vascular and inotropic effects in response to phenylephrine (Phe), acetylcholine (aCh) and angiotensin II (Ang II) when treatments consisting of: (1) live and heat-killed (HK) C. albicans wild-type yeasts; (2) live C. albicans pmr1Δ yeasts (displaying shorter N-linked and O-linked mannans); (3) live C. albicans without N-linked and O-linked mannans; and (4) isolated N-linked and O-linked mannans were administered to the heart. Our results showed that C. albicans WT alters heart coronary perfusion pressure (vascular effect) and left ventricular pressure (inotropic effect) parameters in response to Phe and Ang II but not aCh, and these effects can be reversed by mannose. Similar results were observed when isolated cell walls, live C. albicans without N-linked mannans or isolated O-linked mannans were perfused into the heart. In contrast, C. albicans HK, C. albicans pmr1Δ, C. albicans without O-linked mannans or isolated N-linked mannans were not able to alter the CPP and LVP in response to the same agonists. Taken together, our data suggest that C. albicans interaction occurs with specific receptors on coronary endothelium and that O-linked mannan contributes to a greater extent to this interaction. Further studies are necessary to elucidate why specific receptors preferentially interact with this fungal cell wall structure. Full article

The incidence of invasive fungal infection in ICUs has increased over time, and Candida spp. is the most common cause. Critical care patients are a particular set of patients with a higher risk of invasive fungal infections; this population is characterized by extensive use of medical devices such as central venous lines, arterial lines, bladder catheters, hemodialysis and mechanical intubation. Blood cultures are the gold standard diagnosis; still, they are not an early diagnostic technique. Mannan, anti-mannan antibody, 1,3-β-D-glucan, Candida albicans germ tube antibody, Vitek 2, PNA-FISH, MALDI-TOF, PCR and T2Candida panel are diagnostic promising microbiological assays. Scoring systems are tools to distinguish patients with low and high risk of infection. They can be combined with diagnostic tests to select patients for pre-emptive treatment or antifungal discontinuation. Candidemia is the focus of this narrative review, an approach to contributing factors and diagnosis, with an emphasis on critical care patients. Full article

With the increase in the incidence of fungal infections, and the restrictions of existing antifungal drugs, the development of novel antifungal agents is urgent. Here we prove that AP10W, a short peptide derived from AP-2 complex subunit mu-A, displays conspicuous antifungal activities against the main fungal pathogens of human infections Candida albicans and Aspergillus fumigatus. We also show that AP10W suppresses the fungal biofilm formation, and reduces the pre-established fungal biofilms. AP10W appears to exert its fungicidal activity through a mode of combined actions, including interaction with the fungal cell walls via laminarin, mannan and chitin, enhancement of cell wall permeabilization, induction of membrane depolarization, and increase in intracellular ROS generation. Importantly, we demonstrate that AP10W exhibits little toxicity towards mammalian fibroblasts, and effectively promotes the healing of wounded skins infected by C. albicans. These together indicate that AP10W is a new member of fungicidal agents. It also suggests that AP10W has a considerable potential for future development as a novel antifungal drug. Full article

Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used. Principles and methods of treatment are discussed in this review. The emergence of pan-drug-resistant C. auris strains indicates an insufficient choice of available medications. Further surveillance, alongside the development of diagnostic and therapeutic methods, is essential. Full article

Candidiasis, caused by the opportunistic yeast Candida albicans, is the most common fungal infection today. Resistance of C. albicans to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against C. albicans. After screening 90 potential antifungal compounds from JUNIA, a chemical library, two compounds, 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-3,6-dimethylpyridin-2(1H)-one (PYR) and (Z)-N-(2-(4,6-dimethoxy-1,3,5-triazin-2-yl)vinyl)-4-methoxyaniline (TRI), were identified as having potential antifungal activity. Treatment with PYR and TRI resulted in a significant reduction of C. albicans bioluminescence as well as the number of fungal colonies, indicating rapid fungicidal activity. These two compounds were also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. PYR and TRI had an inhibitory effect on Candida biofilm formation and reduced the thickness of the mannan cell wall. In a Caenorhabditis elegans infection model, PYR and TRI decreased the mortality of nematodes infected with C. albicans and enhanced the expression of antimicrobial genes that promote C. albicans elimination. Overall, PYR and TRI showed antifungal properties against C. albicans by exerting fungicidal activities and enhancing the antimicrobial gene expression of Caenorhabditis elegans. Full article

Candida albicans is maintained as a commensal by immune mechanisms at the oral epithelia. Oral antifungal peptide Histatin 5 (Hst 5) may function in innate immunity, but the specific role Hst 5 plays in C. albicans commensalism is unclear. Since Zn-binding potentiates the candidacidal activity of Hst 5, we hypothesized that Hst 5+Zn would elicit a unique fungal stress response to shape interactions between C. albicans and oral epithelial cells (OECs). We found that Hst 5+Zn but not Hst 5 alone resulted in the activation of cell wall integrity (CWI) signaling, and deletion mutants were then used to determine that CWI-mediated chitin synthesis was protective against killing. Using flow cytometry, we confirmed that Hst 5+Zn-treated cells had significantly elevated levels of cell-wall chitin, mannan and β-1,3 glucan compared to Hst 5-treated cells. We then tested the activation of host signaling components involved in C. albicans cell-wall recognition. The immunoblot assay of C. albicans-exposed oral epithelial cells showed increased activation of EphA2 and NF-κB but not EGFR. Interestingly, C. albicans treated with Hst 5+Zn induced the global suppression of pro-inflammatory cytokine release from OECs, but an increase in negative regulator IL-10. Hst 5+Zn-treated cells were more adherent but ultimately less invasive to OECs than control cells, thus indicating lowered virulence. Therefore, Hst 5+Zn-treated C. albicans cells are discerned by epithelial monolayers, but are less virulent and promote anti-inflammatory signaling, suggesting that Hst 5+Zn in combination could play a role in regulating commensalism of oral C. albicans through cell wall reorganization. Full article

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non-neutropenic sepsis and a high risk of IC from two large tertiary ICUs were prospectively included, during a one-year period. IC was classified as proven, likely, possible or unlikely. The AFSP, diagnostic values of T2Candida and MAg, and the consumption of antifungals were evaluated. An amount of 219 patients with 504 T2Candida/MAg samples were included. IC was classified as proven in 29 (13.2%), likely in 7 (3.2%) and possible in 10 (5.5%) patients. Sensitivity/specificity/PPV/NPV values, comparing proven/likely versus unlikely IC, were 47%/100%/94%/90% for BC alone, 50%/97%/75%/90% for T2Candida alone, and 39%/96%/67%/88% for MAg alone. For the combination of T2Candida/MAg taken ≤3 days after AFT initiation, sensitivity/specificity/PPV/NPV was 70%/90%/63%/93%. T2Candida/MAg contributed to early (<3 days) AFT initiation in 13%, early AFT discontinuation in 25% and abstaining from AFT in 24% of patients. No reduction in overall use of AFT during the study period compared with the previous year was observed. An AFSP based on T2Candida and MAg screening contributed to a reduction of unnecessary treatment, but not overall AFT use. The diagnostic performance of T2Candida was lower than previously reported, but increased if T2Candida was combined with MAg. Full article