Loss of Gst1 enhances resistance to MMS by reprogramming the transcription of DNA damage response genes in a Rad53-dependent manner in Candida albicans.

The DNA damage response is a highly conserved protective mechanism that enables cells to cope with various lesions in the genome. Extensive studies across different eukaryotic cells have identified the crucial roles played by components required for response to DNA damage. When compared to the essential signal transducers and repair factors in the DNA damage response circuitry, the negative regulators and underlying mechanisms of this circuitry have been relatively under-examined. In this study, we investigated Gst1, a putative glutathione transferase in the fungal pathogen Candida albicans. We found that under stress caused by the DNA damage agent MMS, GST1 expression was significantly upregulated, and this upregulation was further enhanced by the loss of the checkpoint kinases and DNA repair factors. Somewhat counterintuitively, deletion of GST1 conferred increased resistance to MMS, potentially via enhancing the phosphorylation of Rad53. Furthermore, overexpression of RAD53 or deletion of GST1 resulted in upregulated transcription of DNA damage repair genes, including CAS1, RAD7, and RAD30, while repression of RAD7 transcription in the GST1 deletion reversed the strain's heightened resistance to MMS. Finally, Gst1 physically interacted with Rad53, and their interaction weakened in response to MMS-induced stress. Overall, our findings suggest a negative regulatory role for GST1 in DNA damage response in C. albicans, and position Gst1 within the Rad53-mediated signaling pathway. These findings hold significant implications for understanding the mechanisms underlying the DNA damage response in this fungal pathogen and supply new potential targets for therapeutic intervention.

Modification of surface topographies to inhibit candida biofilm formation.

The rise of infections associated with indwelling medical devices is a growing concern, often complicated by biofilm formation leading to persistent infections. This study investigates a novel approach to prevent Candida albicans attachment on the surface by altering surface topography. The research focuses on two distinct surface topographies: symmetry (squares) and non-symmetry (lines), created through a direct laser photolithography process on a Cyclic olefin copolymer (COC) surface. The wettability of these patterned surfaces was then examined immediately after fabrication and plasma treatment to mimic the sterilization process of indwelling devices through UV plasma. The results reveal directional wettability in the line pattern and size-dependent wettability in both square and line patterns. Candida albicans were cultured on these surfaces to assess the efficacy of the topography in preventing biofilm formation. The study demonstrates that symmetry and non-symmetry pattern topography inhibit biofilm formation, providing a promising strategy for mitigating Candida-associated infections on medical devices. The research sheds light on the potential of surface modification techniques to enhance the biocompatibility of medical devices and reduce the risk of biofilm-related infections.

Hyphal swelling induced in the phagosome of macrophages.

Macrophages play critical protective roles as sentinels of the innate immune system against fungal infection. It is therefore important to understand the dynamics of the interaction between these phagocytes and their fungal prey. We show here that many of the hyphal apices formed by Candida albicans within the macrophage ceased elongating, and apical and sub-apical hyphal compartments became swollen. Swollen hyphal cell compartments assimilated less Lysotracker-Red than non-swollen compartments, suggesting they had enhanced viability. Staining with florescent dyes suggested that there were higher levels of ß-glucan and chitin in internalized fungal filaments compared to non-internalized hyphae, suggesting active cell wall remodelling within macrophages. These observations suggest that the stresses imposed by macrophages upon the fungus lead to changes in cell wall composition, inhibition of polarised growth and the induction of swelling in hyphal compartments, and that this can prevent or delay loss of viability of hyphal cells within the phagocyte.

BLNK negatively regulates innate antifungal immunity through inhibiting c-Cbl-mediated macrophage migration.

B cell linker protein (BLNK) is crucial for orchestrating B cell receptor-associated spleen tyrosine kinase (Syk) signaling. However, the role of BLNK in Syk-coupled C-type lectin receptor (CLR) signaling in macrophages remains unclear. Here, we delineate that CLRs govern the Syk-mediated activation of BLNK, thereby impeding macrophage migration by disrupting podosome ring formation upon stimulation with fungal ß-glucans or α-mannans. Mechanistically, BLNK instigates its association with casitas B-lineage lymphoma (c-Cbl), competitively impeding the interaction between c-Cbl and Src-family kinase Fyn. This interference disrupts Fyn-mediated phosphorylation of c-Cbl and subsequent c-Cbl-associated F-actin assembly. Consequently, BLNK deficiency intensifies CLR-mediated recruitment of the c-Cbl/phosphatidylinositol 3-kinase complex to the F-actin cytoskeleton, thereby enhancing macrophage migration. Notably, mice with monocyte-specific BLNK deficiency exhibit heightened resistance to infection with Candida albicans, a prominent human fungal pathogen. This resistance is attributed to the increased infiltration of Ly6C+ macrophages into renal tissue. These findings unveil a previously unrecognized role of BLNK for the negative regulation of macrophage migration through inhibiting CLR-mediated podosome ring formation during fungal infections.

Comparative analysis of hydrophobicity and dentin adhesion ability in Candida albicans strains.

OBJECTIVE: Adhesion to dentin is a first step for a successful microbial root canal colonization. Cell hydrophobicity seems to have some influence in the Candida species adhesion to surfaces. To measure cell surface hydrophobicity and to investigate the adherence ability to human dentin among Candida albicans strains isolated from root canal and lingual dorsum via an in vitro study. METHODOLOGY: adhesion was quantified in function of dentin area covered by blastospores and/or hyphae presence detected by epifluorescence microscope. Cell surface hydrophobicity was estimated by assessing the percentage migration of cells from an aqueous phase to a hydrocarbon phase. Contact angles were measured by the sessile drop technique on the dentin surface using a contact angle measurements apparatus. We also examined the correlation between adhesion ability and hydrophobicity. RESULTS: although there was some intra-species variation in cell surface hydrophobicity, most isolates were characterized by moderate hydrophobicity. There was no significant difference in this parameter when the isolation niche was considered. Both root canal and lingual dorsum yeasts were able to adhere to dentin. No association was found between the strains' site of isolation and adhesion. Moreover, cell surface hydrophobicity and adhesion ability were not correlated. CONCLUSION: although hydrophobicity can influence Candida albicans virulence in many ways, this study suggests that this parameter by itself was not a good predictor of adhesion to dentin.

Biofilm formation of Streptococcus mutans, Streptococcus sanguinis, Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus casei, and Candida Albicans on 5 thermoform and 3D printed orthodontic clear aligner and retainer materials at 3 time points: an in vitro study.

INTRODUCTION: Orthodontic clear aligners and retainers have numerous advantages that is making them ever increasingly popular. However, they might, similar to any other oral appliance, contribute to biofilm formation and finally dental caries or white spot lesions or gingival inflammations. The literature on biofilm formation on orthodontic clear appliances is very scarce and limited to a few microorganisms and materials. Therefore, this experimental study evaluated the biofilm formation on 5 thermoformed and 3D printed CAD/CAM orthodontic retainers in 3 intervals. METHODS: In this in vitro study, 345 specimens (270 test discs and 45 negative controls) were created from fabricated retainers. Retainers included a 3D printed CAD/CAM material (Detax) and four thermoformed retainers [Erkodent (polyethylene terephthalate glycol [PETG]); EasyVac (polyethylene); DB (polyester based on terephthalic acid); and Clear Tech]. They were all 1 mm thick, and all completely fabricated, i.e., heated or printed. The discs were placed in 96-well plates. Microorganisms were cultured on 270 discs for 24 h (90 discs), 72 h (90 other discs), and 5 days or 120 h (90 other discs). Biofilm formation of the strains and negative controls was measured using the microtiter plate assay by ELISA reading. The microbes' ability to produce biofilm was categorized based on the comparison of average optical density (OD) of tests versus a cut-off point OD (ODc) calculated as the average of the OD of corresponding negative controls plus 3× its standard deviation: non-biofilm former [OD ≤ ODc], weak biofilm former [ODc < OD ≤ (2 × ODc)], moderate biofilm former [(2 × ODc) < OD ≤ (4 × ODc)], and strong biofilm former [(4 × ODc) < OD]. These were also converted to ranked scores between zero (no biofilm) and 3. The difference between ODs with control ODs were calculated. These were analyzed using 3-way ANOVA, 2-way ANOVA, and Tukey tests (α = 0.05, α = 0.008). RESULTS: The 3-way ANOVA showed that the overall difference among the ΔODs of 5 retainers (all microorganisms and all intervals combined, n = 270) was not significant (F = 1.860, P = 0.119). Nevertheless, the difference among 3 intervals (F = 31.607, P = 0.0000) and the difference among the 6 microorganisms (F = 24.044, P = 0.0000) were significant. According to the Tukey test, the differences between the 1st interval with either of the other two intervals was significant (both P values = 0.000). There were significant differences between Candida albicans with all other organisms (all 5 P values = 0.0000). All other pairwise comparisons were insignificant (all 10 P values ≥ 0.1). After taking the averages of the 3 intervals, the order of the biofilm generation for different materials were as follows: Detax (average score: 1.56), Easyvac (1.67), Erkodent (1.78), Clear Tech (1.83), BD (2.28). CONCLUSIONS: As far as these 6 microorganisms are of concern, there might not be a significant overall difference among the clear retainer materials tested in this study. A significant overall increase was observed between the first and third days, which later did not significantly increase more until day 5. The Candida albicans biofilm was more intense than the tested 5 bacteria, which themselves showed rather similar growth patterns to each other.

Exploring the efficacy of in-vitro low-temperature plasma treatment on single and multispecies dental cariogenic biofilms.

The primary aim of this study was to investigate the impact of treatment with low-temperature plasma (LTP) for varying exposure durations on a multispecies cariogenic biofilm comprising C. albicans, L. casei, and S. mutans, as well as on single-species biofilms of L. casei and C. albicans, cultured on hydroxyapatite discs. Biofilms were treated with LTP-argon at a 10 mm distance for 30 s, 60 s, and 120 s. Chlorhexidine solution (0.12%) and NaCl (0.89%) were used as positive (PC) and negative controls (NC), respectively. Argon flow only was also used as gas flow control (F). Colony-forming units (CFU) recovery and confocal laser scanning microscopy (CLSM) were used to analyze biofilm viability. LTP starting at 30 s of application significantly reduced the viability of multispecies biofilms by more than 2 log10 in all treated samples (p < 0.0001). For single-species biofilms, L. casei showed a significant reduction compared to PC and NC of over 1 log10 at all exposure times (p < 0.0001). In the case of C. albicans biofilms, LTP treatment compared to PC and NC resulted in a significant decrease in bacterial counts when applied for 60 and 120 s (1.55 and 1.90 log10 CFU/mL, respectively) (p < 0.0001). A significant effect (p ≤ 0.05) of LTP in single-species biofilms was observed to start at 60 s of LTP application compared to F, suggesting a time-dependent effect of LTP for the single-species biofilms of C. albicans and L. casei. LTP is a potential mechanism in treating dental caries by being an effective anti-biofilm therapy of both single and multispecies cariogenic biofilms.

Antimicrobial Tolerance in Cross-Kingdom Dual-Species Biofilms Formed by Fungi and Bacteria.

Candida albicans, the most common pathogenic fungus, can form biofilms on the surface of medical devices and often causes bloodstream infections. Biofilms have a complex structure composed of microorganisms and a surrounding extracellular matrix. Biofilms are difficult to treat because they are resistant to antifungal drugs and the host environment. Nearly one in four patients with candidemia have a polymicrobial infection. These polymicrobial biofilms, especially those comprising cross-kingdom species of fungi and bacteria, can lead to long hospital stays and high mortality rates. This review outlines the unique interactions of dual-species biofilms with Candida albicans and the clinically important bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

Mechanisms of action of Lactobacillus spp. in the treatment of oral candidiasis.

Candida albicans is often associated with oral candidiasis, and drug-resistance profiles have contributed to an increase in morbidity and mortality. It is known that Lactobacillus spp. acts by competing for adhesion to the epithelium, absorption of nutrients and modulation of the human microbiota. Therefore, they are important to assist in the host's microbiological balance and reduce the growth of Candida spp. Until now, there have been no reports in the literature of reviews correlating to the use of Lactobacillus spp. in the treatment of oral candidiasis. Thus, this review aims to highlight the mechanisms of action of Lactobacillus spp. and methods that can be used in the treatment of oral candidiasis. This is a study carried out through the databases PubMed Central and Scientific Electronic Library Online, using the following keywords: Oral Candidiasis and Lactobacillus. Original articles about oral candidiasis were included, with both in vitro and in vivo analyses, and published from 2012 to 2022. Lactobacillus rhamnosus was the most common microorganism used in the experiments against Candida, acting mainly in the reduction of biofilm, filamentation, and competing for adhesion sites of Candida spp. Among in vivo studies, most researchers used immunosuppressed mouse modelsof Candida infection. The studies showed that Lactobacillus has a great potential as a probiotic, acting mainly in the prevention and treatment of mucosal diseases. Thus, the use of Lactobacillus may be a good strategy for the treatment of oral candidiasis.

Antibiotics stimulates the development of persistent cells in biofilms of Candida albicans bloodstream isolates.

Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.

Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.

Fungal Attachment-Resistant Polymers for the Additive Manufacture of Medical Devices.

This study reports the development of the first copolymer material that (i) is resistant to fungal attachment and hence biofilm formation, (ii) operates via a nonkilling mechanism, i.e., avoids the use of antifungal actives and the emergence of fungal resistance, (iii) exhibits sufficient elasticity for use in flexible medical devices, and (iv) is suitable for 3D printing (3DP), enabling the production of safer, personalized medical devices. Candida albicans (C. albicans) can form biofilms on in-dwelling medical devices, leading to potentially fatal fungal infections in the human host. Poly(dimethylsiloxane) (PDMS) is a common material used for the manufacture of medical devices, such as voice prostheses, but it is prone to microbial attachment. Therefore, to deliver a fungal-resistant polymer with key physical properties similar to PDMS (e.g., flexibility), eight homopolymers and 30 subsequent copolymers with varying glass transition temperatures (Tg) and fungal antiattachment properties were synthesized and their materials/processing properties studied. Of the copolymers produced, triethylene glycol methyl ether methacrylate (TEGMA) copolymerized with (r)-α-acryloyloxy-ß,ß-dimethyl-γ-butyrolactone (AODMBA) at a 40:60 copolymer ratio was found to be the most promising candidate by meeting all of the above criteria. This included demonstrating the capability to successfully undergo 3DP by material jetting, via the printing of a voice prosthesis valve-flap using the selected copolymer.

Veillonella parvula promotes root caries development through interactions with Streptococcus mutans and Candida albicans.

Root caries is a subtype of dental caries that predominantly impacts older adults. The occurrence and progression of root caries are associated with the homeostasis of dental plaque biofilm, and microbial synergistic and antagonistic interactions in the biofilm play a significant role in maintaining the oral microecological balance. The objective of the current study was to investigate the role of Veillonella parvula in the microbial interactions and the pathogenesis of root caries. The analysis of clinical samples from patients with/without root caries revealed that Veillonella and V. parvula were abundant in the saliva of patients with root caries. More importantly, a significantly increased colonization of V. parvula was observed in root carious lesions. Further in vitro biofilm and animal study showed that V. parvula colonization increased the abundance and virulence of Streptococcus mutans and Candida albicans, leading to the formation of a polymicrobial biofilm with enhanced anti-stress capacity and cariogenicity, consequently exacerbating the severity of carious lesions. Our results indicate the critical role of V. parvula infection in the occurrence of root caries, providing a new insight for the etiological investigation and prevention of root caries.

Synergistic effects of quorum-sensing molecules and antimicrobials against Candida albicans and Pseudomonas aeruginosa biofilms: in vitro and in vivo studies.

BACKGROUND: Candida albicans can form polymicrobial biofilms with other microorganisms, such as Pseudomonas aeruginosa, at infection sites. OBJECTIVES: As biofilms are highly resistant to antibiotics there is a need for new antibiofilm agents that have unique targets and modes of action. METHODS: In this study the antibiofilm effects of two quorum-sensing molecules (QSMs), farnesol and tyrosol, were investigated alone and in combination with antibiotics (aztreonam, colistin, tobramycin) and antifungals (fluconazole, amphotericin B, caspofungin), against single- and dual-species biofilms of C. albicans and P. aeruginosa in in vitro and in vivo systems. RESULTS: It was observed that QSMs alone, especially farnesol, showed at least a 1-log reduction against preformed single- and dual-species biofilms of C. albicans and P. aeruginosa. Combination of QSMs with colistin or fluconazole was found to be effective against both single- and dual-species biofilms in vitro. Increased survival was observed in C. elegans when treated with colistin or fluconazole in combination with QSMs, compared with no treatment. Additionally, the QSMs and colistin and farnesol combinations effectively inhibited biofilm formation by C. albicans and P. aeruginosa on bronchial epithelial cells, and reduced IL-1ß expression in lung bronchial epithelial cells. CONCLUSIONS: There is a need for effective treatments for bacterial-fungal biofilm infections and, to our knowledge, there have been no studies of QSMs and antimicrobial combinations against dual-species biofilms involving C. albicans and P. aeruginosa. Hence these findings will make a significant contribution to the literature.

ASLdC3: A Derivative of Acidic Sophorolipid Disrupts Mitochondrial Function, Induces ROS Generation, and Inhibits Biofilm Formation in Candida albicans.

Fungal infections account for more than 140 million cases of severe and life-threatening conditions each year, causing approximately 1.7 million deaths annually. Candida albicans and related species are the most common human fungal pathogens, causing both superficial (mucosal and cutaneous) and life-threatening invasive infections (candidemia) with a 40-75% mortality rate. Among many virulence factors of Candida albicans, morphological transition from yeast to hyphae, secretion of hydrolytic enzymes, and formation of biofilms are considered to be crucial for pathogenicity. However, the arsenals for the treatment against these pathogens are restricted to only a few classes of approved drugs, the efficacy of which is being compromised by host toxicity, fungistatic activity, and the emergence of drug resistance. In this study, we have described the development of a molecule, exhibiting excellent antifungal activity (MIC 8 µg/mL), by tailoring acidic sophorolipids with aryl alcohols via enzyme catalysis. This novel derivative, ASLdC3, is a surface-active compound that lowers the surface tension of the air-water interface up to 2-fold before reaching the critical micelle concentration of 25 µg/mL. ASLdC3 exhibits excellent antibiofilm properties against Candida albicans and other nonalbicans Candida species. The molecule primarily exhibits its antifungal activity by perturbing mitochondrial function through the alteration of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS). The ROS damages fungal cell membrane function and cell wall integrity, eventually leading to cell death. ASLdC3 was found to be nontoxic in in vitro assay and nonhemolytic. Besides, it does not cause toxicity in the C. elegans model. Our study provides a valuable foundation for the potential of acidic sophorolipid as a nontoxic, biodegradable precursor for the design and synthesis of novel molecules for use as antimicrobial drugs as well as for other clinical applications.

Vicia ervilia lectin (VEA) has an antibiofilm effect on both Gram-positive and Gram-negative pathogenic bacteria.

Bacterial growing resistance to antibiotics poses a critical threat to global health. This study investigates, for the first time, the antibiofilm properties of Vicia ervilia agglutinin (VEA) from six different V. ervilia accessions against pathogenic bacteria, and the yeast Candida albicans. In the absence of antimicrobial properties, purified VEA significantly inhibited biofilm formation, both in Gram-positive and Gram-negative bacteria, but not in C. albicans. With an inhibitory concentration ranging from 100 to 500 µg/ml, the VEA antibiofilm activity was more relevant against the Gram-positive bacteria Streptococcus aureus and Staphylococcus epidermidis, whose biofilm was reduced up to 50% by VEA purified from accessions #5 and #36. VEA antibiofilm variability between accessions was observed, likely due to co-purified small molecules rather than differences in VEA protein sequences. In conclusion, VEA seed extracts from the accessions with the highest antibiofilm activity could represent a valid approach for the development of an effective antibiofilm agent.

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia.

Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans into the patient's lower airways. Currently, there is a lack of accurate in vitro models of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates the biofilm formation of these pathogens in a host-mimicking environment and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilated airway mucus medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-scanning electron microscopy were employed to characterize the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved the biofilm eradication of all pathogens. Our in vitro endotracheal tube model informs on fundamental microbiology in the ventilator-associated pneumonia context and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.

"Glycans in Trained Immunity: Educators of innate immune memory in homeostasis and disease".

Trained Immunity is defined as a biological process normally induced by exogenous or endogenous insults that triggers epigenetic and metabolic reprogramming events associated with long-term adaptation of innate immune cells. This trained phenotype confers enhanced responsiveness to subsequent triggers, resulting in an innate immune "memory" effect. Trained Immunity, in the past decade, has revealed important benefits for host defense and homeostasis, but can also induce potentially harmful outcomes associated with chronic inflammatory disorders or autoimmune diseases. Interestingly, evidence suggest that the "trainers" prompting trained immunity are frequently glycans structures. In fact, the exposure of different types of glycans at the surface of pathogens is a key driver of the training phenotype, leading to the reprogramming of innate immune cells through the recognition of those glycan-triggers by a variety of glycan-binding proteins (GBPs) expressed by the immune cells. ß-glucan or mannose-enriched structures in Candida albicans are some of the examples that highlight the potential of glycans in trained immunity, both in homeostasis and in disease. In this review, we will discuss the relevance of glycans exposed by pathogens in establishing key immunological hubs with glycan-recognizing receptors expressed in immune cells, highlighting how this glycan-GBP network can impact trained immunity. Finally, we discuss the power of glycans and GBPs as potential targets in trained immunity, envisioning potential therapeutic applications.

The positive impact of Streptococcus mutans on the growth of Candida albicans within mixed-species biofilms and implications to dental health.

INTRODUCTION: Candida albicans and Streptococcus mutans co-exist in biofilms in the oral cavity. In this study, the impact of S. mutans on the growth of C. albicans within a mixed-species biofilm was examined. MATERIALS AND METHODS: Single species C. albicans biofilms and mixed species biofilms containing C. albicans and S. mutans at 1:3 and 1:10 ratios were constructed in 6-well microtiter plates. After 24 hours of incubation, the density of resuspended biofilm cells was determined as CFU/ml and used to compare the growth of C. albicans in single species and mixed species biofilms. RESULTS: The CFU/ml of C. albicans in mixed-species biofilms was found to be higher than that in single-species biofilms. CONCLUSION: S. mutans promotes the growth of C. albicans in a co-inhabited biofilm.

Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.

An important host defence mechanism against pathogens is intracellular killing, which is achieved through phagocytosis, a cellular process for engulfing and neutralizing extracellular particles. Phagocytosis results in the formation of matured phagolysosomes, which are specialized compartments that provide a hostile environment and are considered the end point of the degradative pathway. However, all fungal pathogens studied to date have developed strategies to manipulate phagosomal function directly and also indirectly by redirecting phagosomes from the degradative pathway to a non-degradative pathway with the expulsion and even transfer of pathogens between cells. Here, using the major human fungal pathogens Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum as examples, we discuss the processes involved in host phagosome-fungal pathogen interactions, with a focus on fungal evasion strategies. We also discuss recent approaches to targeting intraphagosomal pathogens, including the redirection of phagosomes towards degradative pathways for fungal pathogen eradication.

Lavandula dentata L. essential oil: a promising antifungal and antibiofilm agent against oral Candida albicans.

Candida albicans is the main fungal species involved in oral candidiasis, and its increasing resistance to pharmacological treatment encourages the search for improved antifungal agents. Lavandula dentata L. essential oil (LD-EO) has been recognized for its antimicrobial activity, but little is known about its role against oral C. albicans. This study evaluated the antifungal and antibiofilm activities, mechanisms of action, and toxicity of LD-EO from Brazil against oral strains of C. albicans. Antifungal activity was assessed based on Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), association study with miconazole (Checkerboard method), and sorbitol and ergosterol assays. Inhibition of biofilm formation and disruption of preformed biofilm were considered when studying the effects of the product. Additionally, the toxicity of LD-EO was evaluated by a hemolysis assay on human erythrocytes. Phytochemical analysis by gas chromatography-mass spectrometry identified eucalyptol (33.1%), camphor (18.3%), and fenchone (15.6%) as major constituents. The test substance showed mainly fungicidal activity (MIC100 = 8 µg/mL; MFC = 16 µg/mL), including against two miconazole-resistant isolates of C. albicans. The effects of LD-EO were synergistic with those of miconazole and appeared not to involve damage to the fungal cell wall or plasma membrane. Its effectiveness in inhibiting biofilm formation was higher than the effect of disrupting preformed biofilm. Finally, the product exhibited low hemolytic activity at MIC. Based on the favorable and novel results described here, LD-EO could constitute a promising therapeutic alternative for oral candidiasis, including miconazole-resistant cases.