Human Mucosal Surfaces Research Articles

Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies.

The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants' first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.

Granulicatella adiacens Bacterial Infection After Pancreatectomy Whipple's Procedure.

Background: Granulicatella adiacens inhabits the oral cavity, urogenital, and gastrointestinal tracts and is a typical commensal of human mucosal surfaces. It rarely causes disease. Identification of these gram-positive cocci can be challenging. Case Report: In a 58-year-old male in an oncology center, we report the first occurrence of bacterial infection caused by G. adiacens. After a precise diagnosis of the infection, the patient received effective treatment. Conclusion: Owing to a lack of sufficient diagnostic tools, G. adiacens may be a more notable pathogen than has been previously identified. Sensitivity testing standards are desperately needed.

Dual species transcriptomics reveals conserved metabolic and immunologic processes in interactions between human neutrophils and Neisseria gonorrhoeae.

Neisseria gonorrhoeae (the gonococcus, Gc) causes the sexually transmitted infection gonorrhea. Gc is a prominent threat to human health by causing severe lifelong sequelae, including infertility and chronic pelvic pain, which is amplified by the emergence of "superbug" strains resistant to all current antibiotics. Gc is highly adapted to colonize human mucosal surfaces, where it survives despite initiating a robust inflammatory response and influx of polymorphonuclear leukocytes (PMNs, neutrophils) that typically clear bacteria. Here, dual-species RNA-sequencing was used to define Gc and PMN transcriptional profiles alone and after infection. Core host and bacterial responses were assessed for two strains of Gc and three human donors' PMNs. Comparative analysis of Gc transcripts revealed overlap between Gc responses to PMNs, iron, and hydrogen peroxide; 98 transcripts were differentially expressed across both Gc strains in response to PMN co-culture, including iron-responsive and oxidative stress response genes. We experimentally determined that the iron-dependent TbpB is suppressed by PMN co-culture, and iron-limited Gc have a survival advantage when cultured with PMNs. Analysis of PMN transcripts modulated by Gc infection revealed differential expression of genes driving cell adhesion, migration, inflammatory responses, and inflammation resolution pathways. Production of pro-inflammatory cytokines, including IL1B and IL8, the adhesion factor ICAM1, and prostaglandin PGE2 were induced in PMNs in response to Gc. Together, this study represents a comprehensive and experimentally validated dual-species transcriptomic analysis of two isolates of Gc and primary human PMNs that gives insight into how this bacterium survives innate immune onslaught to cause disease.

Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection.

The opportunistic fungal pathogen Candida albicans thrives on human mucosal surfaces as a harmless commensal, but frequently causes infections under certain predisposing conditions. Translocation across the intestinal barrier into the bloodstream by intestine-colonizing C. albicans cells serves as the main source of disseminated candidiasis. However, the host and microbial mechanisms behind this process remain unclear. In this study we identified fungal and host factors specifically involved in infection of intestinal epithelial cells (IECs) using dual-RNA sequencing. Our data suggest that host-cell damage mediated by the peptide toxin candidalysin-encoding gene ECE1 facilitates fungal zinc acquisition. This in turn is crucial for the full virulence potential of C. albicans during infection. IECs in turn exhibit a filamentation- and damage-specific response to C. albicans infection, including NFκB, MAPK, and TNF signaling. NFκB activation by IECs limits candidalysin-mediated host-cell damage and mediates maintenance of the intestinal barrier and cell-cell junctions to further restrict fungal translocation. This is the first study to show that candidalysin-mediated damage is necessary for C. albicans nutrient acquisition during infection and to explain how IECs counteract damage and limit fungal translocation via NFκB-mediated maintenance of the intestinal barrier.

P1229 The Role and Niche-Specific Adaptation of Malassezia in patients with Ulcerative colitis

Abstract Background Accumulating evidence has underscored the role of gut fungal microbiota (mycobiota) in the development of inflammatory bowel disease. We aimed to isolate a Malassezia strain directly from the human intestine mucosal surface from the patients with ulcerative colitis (UC) and investigated its genome and virulence in comparison with the same fungal species isolated from the human skin. Methods Mucosal lavage samples were collected separately from colonic areas with and without inflammation in patients with UC. Samples from healthy individuals (HT) were obtained in the same manner as from patients with UC at sigmoid or descending colon. Skin samples were taken from HT in our previous work. DNA was extracted from these lavage samples, and fungal isolation was conducted using PCR amplification with ITS4 and ITS5 primers. Comprehensive analysis and comparison of the genomes, transcriptomes, and virulence between M. globosa gut isolates and those of M. globosa strains isolated from the skin were performed. To determine the contribution of M. globosa gut isolates to exacerbating inflammation, 1107 fungal cells were orally gavaged to DSS-induced colitis mouse model for three days. Results Total 56 and 11 intestinal water-lavage samples from 29 UC patients and 11 HT were obtained respectively. The α- and b-diversities of mycobiota showed no significant differences between the groups, patients with UC vs. HT or the sites with inflammation vs. non-inflammation of the patient with UC. Malassezia was the fifth most frequently found fungal genus throughout the samples, and live fungal strains belong to 28 and 7 different species were isolated from the patients with UC and HT, respectively. The patients with UC tend to have higher frequency of M. globosa and M. restricta than HT in their gut mucosal surface with inflammation. Whole genome sequencing showed no specific genomic characteristics between gut-isolated M. globosa and skin-isolated M. globosa. However, gut-isolated M. globosa were suffered more from the higher oxygen levels than the skin isolates in different oxygen concentrations. In a mouse model, gut-isolated M. globosa exhibited a more pronounced exacerbation of DSS-induced colitis and elevated production of inflammatory cytokines, including TNF-a, IL-6, IL-12p40, IL-1b, and IL-18, while the skin isolates showed no difference compared to the negative control (Figure). Conclusion Our data shed new light on the pivotal role of M. globosa in the pathogenesis of UC, highlighting the potential influence of niche-specific adaptations on the virulence of this fungus. These findings provide critical insights into the complex interplay between the member of the gut mycobiota and host health.

Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver.

Immunosenescence refers to the development of weakened and/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although Klebsiella pneumoniae is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why K. pneumoniae is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host's intestinal immune response to K. pneumoniae varies with age. To this end, the study analyzed an in vivo K. pneumoniae infection model using aged mice, as well as an in vitro K. pneumoniae infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize K. pneumoniae, inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under K. pneumoniae infection due to decreasing intestinal mucosal macrophages; therefore, K. pneumoniae can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of K. pneumoniae from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why K. pneumoniae can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.

Cryptosporidium parvum hijacks a host's long noncoding RNA U90926 to evade intestinal epithelial cell-autonomous antiparasitic defense.

Cryptosporidium is a zoonotic apicomplexan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans. It is an important opportunistic pathogen in AIDS patients and a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. The intestinal epithelial cells provide the first line of defense against Cryptosporidium infection and play a central role in activating and regulating the host's antiparasitic response. Increasing evidence suggests that long noncoding RNAs (lncRNAs) participate in host-pathogen interactions and play a regulatory role in the pathogenesis of diseases but the underlying molecular mechanisms are not fully understood. We previously identified a panel of host lncRNAs that are upregulated in murine intestinal epithelial cells following Cryptosporidium infection, including U90926. We demonstrate here that U90926 is acting in a pro-parasitic manner in regulating intestinal epithelial cell-autonomous antiparasitic defense. Inhibition of U90926 resulted in a decreased infection burden of the parasite while overexpression of U90926 showed an increase in infection burden in cultured murine intestinal epithelial cells. Induction of U90926 suppressed transcription of epithelial defense genes involved in controlling Cryptosporidium infection through epigenetic mechanisms. Specifically, transcription of Aebp1, which encodes the Aebp1 protein, a potent modulator of inflammation and NF-κB signaling, was suppressed by U90926. Gain- or loss-of-function of Aebp1 in the host's epithelial cells caused reciprocal alterations in the infection burden of the parasite. Interestingly, Cryptosporidium carries the Cryptosporidium virus 1 (CSpV1), a double-stranded (ds) RNA virus coding two dsRNA fragments, CSpV1-dsRdRp and CSpV1-dsCA. Both CSpV1-dsRdRp and CSpV1-dsCA can be delivered into infected cells as previously reported. We found that cells transfected with in vitro transcribed CSpV1-dsCA or CSpV1-dsRdRp displayed an increased level of U90926, suggesting that CSpV1 is involved in the upregulation of U90926 during Cryptosporidium infection. Our study highlights a new strategy by Cryptosporidium to hijack a host lncRNA to suppress epithelial cell-autonomous antiparasitic defense and allow for a robust infection.

Prevotella buccae bacteremia in an immunocompetent host – A case report and review of the literature

Prevotella, a Gram-negative rod, is a normal commensal found on human mucosal surfaces. While infection with Prevotella spp. among immunocompromised individuals is common, among immunocompetent individuals, infection with this species is rare. We report an unusual case of a patient with Prevotella buccae bacteremia and we have conducted a short review of the literature on prior reports of P. buccae bacteremia.

Candida albicans selection for human commensalism results in substantial within-host diversity without decreasing fitness for invasive disease.

Candida albicans is a frequent colonizer of human mucosal surfaces as well as an opportunistic pathogen. C. albicans is remarkably versatile in its ability to colonize diverse host sites with differences in oxygen and nutrient availability, pH, immune responses, and resident microbes, among other cues. It is unclear how the genetic background of a commensal colonizing population can influence the shift to pathogenicity. Therefore, we examined 910 commensal isolates from 35 healthy donors to identify host niche-specific adaptations. We demonstrate that healthy people are reservoirs for genotypically and phenotypically diverse C. albicans strains. Using limited diversity exploitation, we identified a single nucleotide change in the uncharacterized ZMS1 transcription factor that was sufficient to drive hyper invasion into agar. We found that SC5314 was significantly different from the majority of both commensal and bloodstream isolates in its ability to induce host cell death. However, our commensal strains retained the capacity to cause disease in the Galleria model of systemic infection, including outcompeting the SC5314 reference strain during systemic competition assays. This study provides a global view of commensal strain variation and within-host strain diversity of C. albicans and suggests that selection for commensalism in humans does not result in a fitness cost for invasive disease.

Serum Level of Antibodies Against Novel Acinetobacter Baumannii OmpA-selected Peptides in ICU Staff: Promise for the Future of Vaccine Development.

Extensively drug-resistant Acinetobacter baumannii is considered one of the most dangerous threats to global health, requiring novel therapeutic interventions. The outer membrane protein A (OmpA) is an immunogenic agent that triggers immune responses. The current study evaluated serum antibody levels against previously determined immunogenic OmpA peptides from A baumannii in ICU staff. Serum samples were collected from 62 ICU staff members (representing the exposed group), healthy controls (representing the nonexposed group), and patients with systemic lupus erythematosus (SLE) (as controls for nonspecific antibody reactions). After excluding the cross-reactive antibodies via Escherichia coli lysate pretreatment, all the samples were assessed in the vicinity of A baumannii lysate by enzyme-linked immunosorbent assay (ELISA). All the positive samples were assessed for interaction with previously designed and selected peptides using ELISA. The protective potential of positive serum antibodies was surveyed in vitro using an opsonophagocytic study. The most antibody positive samples against one of the dominant peptides were determined in the ICU personnel (75%). SLE serum samples did not react with candidate peptides. The strongest positive reaction was observed in serum treatment with one of the OmpA peptides (No. 5) with significant differences compared to other designed peptides. Our findings showed that ICU samples have substantially higher antibody levels than the nonexposed group; Positive samples show strong results in the opsonophagocytosiis assay. This study demonstrates A baumannii colonization at human mucosal surfaces, especially in exposed healthy workers. Novel OmpA-derived peptides could be used to identify immunogenic vaccine candidates. Therefore, more studies are needed before this peptide and antibody levels are used in diagnosis, prevention, or treatment.

Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils.

Neisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered bacteria predominantly express phase-variable, surface-expressed opacity-associated (Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc survival when exposed to human neutrophils ex vivo. Here, we made the unexpected observation that incubation with normal human serum, which is found in inflamed mucosal secretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly linked this phenomenon to a novel complement-independent function for C4b-binding protein (C4BP). When bound to the bacteria, C4BP was necessary and sufficient to suppress Gc-induced neutrophil reactive oxygen species production and prevent neutrophil phagocytosis of Opa+ Gc. This research identifies for the first time a complement-independent role for C4BP in enhancing the survival of a pathogenic bacterium from phagocytes, thereby revealing how Gc exploits inflammatory conditions to persist at human mucosal surfaces.

Evaluation of Candida albicans biofilm formation on conventional and computer-aided-design/computer-aided manufacturing (CAD/CAM) denture base materials.

The human mouth mucosal surface is colonized by indigenous microflora, which normally maintains an ecological balance among different species. However, certain environmental or biological factors may disrupt this balance, leading to microbial diseases. Candida albicans biofilms are formed on indwelling medical devices and have an association with both oral and invasive candidiasis. This study aimed to compare the amount of adherent C. albicans and the biofilm formed on different denture base materials. The adhesion of C. albicans to denture base materials is widely recognized as the main reason for the development of denture stomatitis. In total, 56 polymethyl methacrylate (PMMA) acrylic resin disc-shaped samples were divided into four groups as follows: 1) chemically polymerized PMMA, 2) heat-polymerized PMMA, 3) computer-aided design and computer-aided manufacturing (CAD/CAM) PMMA in high polish, and 4) CAD/CAM resins in glazed form. The adherent cells and formation of C. albicans strains (562, 1905, 1912, and 1949) biofilm were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method and use of a microplate reader. Moreover, morphological alterations of C. albicans cells were investigated using scanning electron microscopy (SEM). The biofilm formation was significantly lower on CAD/CAM acrylic resins, compared to conventional denture base materials. The obtained results were confirmed by the SEM images of C. albicans biofilms. CAD/CAM PMMA-based polymers may be preferable to inhibit C. albicans biofilm formation and reduce Candida-associated denture stomatitis in long-term use. Based on the findings, the CAD/CAM technique can be used as an efficient technique for denture fabrication as it inhibits microbial accumulation, and consequently, microbial biofilm.

Targeting Virulence Factors of Candida albicans with Natural Products.

Natural products derived from natural resources, including nutritional functional food, play an important role in human health. In recent years, the study of anti-fungal and other properties of agri-foods and derived functional compounds has been a hot research topic. Candida albicans is a parasitic fungus that thrives on human mucosal surfaces, which are colonized through opportunistic infection. It is the most prevalent cause of invasive fungal infection in immunocompromised individuals, resulting in a wide variety of clinical symptoms. Moreover, the efficacy of classical therapeutic medications such as fluconazole is often limited by the development of resistance. There is an ongoing need for the development of novel and effective antifungal therapy and medications. Infection of C. albicans is influenced by a great quantity of virulence factors, like adhesion, invasion-promoting enzymes, mycelial growth, and phenotypic change, and among others. Furthermore, various natural products especially from food sources that target C. albicans virulence factors have been researched, providing promising prospects for C. albicans prevention and treatment. In this review, we discuss the virulence factors of C. albicans and how functional foods and derived functional compounds affect them. Our hope is that this review will stimulate additional thoughts and suggestions regarding nutritional functional food and therapeutic development for patients afflicted with C. albicans.

P311 First reported case of Cladosporium liver abscess in immunocompromised host

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground: Cladosporium species are ubiquitous, saprobic, dematiaceous fungi that are infrequently associated with human opportunistic infections. They are usually associated with allergic rhinitis, asthma, localized superficial, and deep cutaneous and subcutaneous lesions, but rarely cause disseminated infection, known as phaeohyphomycoses.Case Description: We report a case of Cladosporium liver abscess in an immunocompromised host. A 39-year-old male with a history of multiple sexual partners was newly diagnosed with human immunodeficiency virus and was antiretroviral therapy naïve. He presented with epigastric and right hypochondriac pain, associated with abdominal distension for 3 months. On examination, he was jaundiced with hepatomegaly. Full blood count showed leukocytosis with neutrophilia (TWC 14.3 × 109/l with ANC 11.2 × 109/l). The liver function test shows hyperbilirubinemia with obstructive features. (Total bilirubin 101.9 μmol/l, direct bilirubin 78.8 μmol/l, ALT 87 U/l, AST 168 U/l, ALP 383 U/l, INR: 1.37). Baseline CD4 was 41 cells/ul, and HIV viral load was >10 000 000 copies/mL.CECT 4-phase liver shows enlarged liver with smooth lobulated margin, measured 22.5 cm. Multiple large round hypodense masses of varying sizes were seen scattered in both liver lobes. The largest mass is in segment VII measuring 5.8 × 7.7 × 8.8 cm. Liver biopsy showed evidence of diffuse large B cell lymphoma while tissue fungal culture grew Cladosporium sp. Antifungal susceptibility testing showed a low MIC range for posaconazole, voriconazole, and itraconazole while terbinafine was not tested. Patient received tablet voriconazole 200 mg BD for 3 months. He was also initiated on chemotherapy antiretroviral therapy at the same time with the regime of T. Tenofovir disoproxil fumarate/emtricitabine 1 tablet once daily and tablet dolutegravir 50 mg once daily. A repeated PET-CT done 3 months later during chemotherapy shows residual hypodense liver lesions.Discussion: A wide range of fungi can be found on various human mucosal surfaces, such as lungs, vaginal tract, urinary tract, oral cavity, intestines, and skin. The community of commensal fungi interacts with commensal bacteria and the host. Changes in the commensal fungi have a significant impact on host health and are associated with pathological conditions. Cladosporium was reported as one of the commensal fungi. Reports of invasive Cladosporium infection are extremely rare with variable presentation. There were previous case reports of Cladosporium infection of the central nervous system, lung, and skin but no liver abscess has been reported yet. Fungal hepatic abscesses are not uncommon among immunocompromised hematological malignancy patients, especially those with leukemia and prolonged neutropenia. Azoles, particularly itraconazole, and posaconazole have good activity against Cladosporium species, although voriconazole displayed variable activity. This is consistent with our case whereby itraconazole and posaconazole demonstrate the lowest MIC as compared to voriconazole. However, voriconazole was chosen instead of itraconazole for coverage against the possibility of Aspergillus appearing later. In our case, the patient showed a good response to voriconazole.ConclusionThe choice of antifungal will depend on susceptibility testing, organ involvement, tissue bioavailability, drug-drug interaction, and patients’ clinical risk factors; whereas the duration of treatment is guided by radiological resolution and control of risk factors.

Disinfection and decontamination in the context of SARS-CoV-2-specific data.

Given the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) as witnessed early in the coronavirus disease 2019 (COVID‐19) pandemic, concerns arose with the existing methods for virus disinfection and decontamination. The need for SARS‐CoV‐2‐specific data stimulated considerable research in this regard. Overall, SARS‐CoV‐2 is practically and equally susceptible to approaches for disinfection and decontamination that have been previously found for other human or animal coronaviruses. The latter have included techniques utilizing temperature modulation, pH extremes, irradiation, and chemical treatments. These physicochemical methods are a necessary adjunct to other prevention strategies, given the environmental and patient surface ubiquity of the virus. Classic studies of disinfection have also allowed for extrapolation to the eradication of the virus on human mucosal surfaces by some chemical means. Despite considerable laboratory study, practical field assessments are generally lacking and need to be encouraged to confirm the correlation of interventions with viral eradication and infection prevention. Transparency in the constitution and use of any method or chemical is also essential to furthering practical applications.

Functionality of the human antibody response to Candida albicans

ABSTRACT Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells are regarded as major players in the defense against pathogenic C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. In this study, we show that human serum antibodies are able to enhance the association of human THP-1 monocyte-like cells with C. albicans cells. Human serum antibodies are also capable of inhibiting the adherence and damage dealt to epithelial cells. Furthermore, human serum antibodies impair C. albicans invasion of human oral epithelial cells by blocking induced endocytosis and consequently host cell damage. While aspartic proteases secreted by C. albicans are able to cleave human IgG, this process does not appear to affect the protective function of human antibodies. Thus, humans are equipped with a robust antibody response to C. albicans, which can enhance antifungal activities and prevent fungal-mediated epithelial damage.

PLASMA COAGULATING AND NON-COAGULATING STAPHYLOCOCCUS SPP. IN SKIN SAMPLES FROM DOGS AND THEIR RESISTANCE TO ANTIBIOTICS

Staphylococci are human and animal mucosal surface and skin commensals that can cause a variety of infections, such as purulent skin infections, otitis externa, pyoderma, urinary tract infections, and postoperative infections. Dog skin is one of the protective barriers for animals. However, dogs can have and transmit a variety of microorganisms on their skin, including staphylococci. Most studies have compared plasma coagulating and non-coagulating Staphylococcus spp. by dog breeds, sex, and coat length. The aim – to identify plasma coagulating and non-coagulating Staphylococcus spp. in skin samples from dogs and its resistance to antibiotics by place of residence. Staphylococci were detected in more than half of the samples tested, one third of which were plasma coagulating and the remaining two thirds were non-coagulating plasma. Plasma non-coagulating staphylococci were mainly increased among dogs living at home and plasma coagulating – among dogs living outdoors, the difference between these groups is statistically significant. Staphylococcus aureus was predominantly resistant to penicillin and clindamycin, while plasma non-coagulants were resistant to fusidic acid.

A Fungal Transcription Regulator of Vacuolar Function Modulates Candida albicans Interactions with Host Epithelial Cells.

ABSTRACTMicroorganisms typically maintain cellular homeostasis despite facing large fluctuations in their surroundings. Microbes that reside on human mucosal surfaces may experience significant variations in nutrient and ion availability as well as pH. Whether the mechanisms employed by these microbial cells to sustain homeostasis directly impact on the interplay with the host’s mucosae remains unclear. Here, we report that the previously uncharacterized transcription regulator ZCF8 in the human-associated yeast Candida albicans maintains vacuole homeostasis when the fungus faces fluctuations in nitrogen. Genome-wide identification of genes directly regulated by Zcf8p followed by fluorescence microscopy to define their subcellular localization uncovered the fungal vacuole as a top target of Zcf8p regulation. Deletion and overexpression of ZCF8 resulted in alterations in vacuolar morphology and luminal pH and rendered the fungus resistant or susceptible to nigericin and brefeldin A, two drugs that impair vacuole and associated functions. Furthermore, we establish that the regulator modulates C. albicans attachment to epithelial cells in a manner that depends on the status of the fungal vacuole. Our findings, therefore, suggest that fungal vacuole physiology regulation is intrinsically linked to, and shapes to a significant extent, the physical interactions that Candida cells establish with mammalian mucosal surfaces.

Bioprospecting Antimicrobials from Lactiplantibacillus plantarum: Key Factors Underlying Its Probiotic Action.

Lactiplantibacillus plantarum (L. plantarum) is a well-studied and versatile species of lactobacilli. It is found in several niches, including human mucosal surfaces, and it is largely employed in the food industry and boasts a millenary tradition of safe use, sharing a long-lasting relationship with humans. L. plantarum is generally recognised as safe and exhibits a strong probiotic character, so that several strains are commercialised as health-promoting supplements and functional food products. For these reasons, L. plantarum represents a valuable model to gain insight into the nature and mechanisms of antimicrobials as key factors underlying the probiotic action of health-promoting microbes. Probiotic antimicrobials can inhibit the growth of pathogens in the gut ensuring the intestinal homeostasis and contributing to the host health. Furthermore, they may be attractive alternatives to conventional antibiotics, holding potential in several biomedical applications. The aim of this review is to investigate the most relevant papers published in the last ten years, bioprospecting the antimicrobial activity of characterised probiotic L. plantarum strains. Specifically, it focuses on the different chemical nature, the action spectra and the mechanisms underlying the bioactivity of their antibacterial and antiviral agents. Emerging trends in postbiotics, some in vivo applications of L. plantarum antimicrobials, including strengths and limitations of their therapeutic potential, are addressed and discussed.