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Increased use of implanted medical devices, use of immunosuppressants and an ageing population have driven the rising frequency of fungal biofilm-related diseases. Fungi are now recognized by the World Health Organization (WHO) as an emergent threat to human health, with most medically important species defined as critical or high-priority organisms capable of forming biofilms. Although we strive for a better understanding of diagnostic and therapeutic approaches to detect and treat these fungal diseases more generally, the issue of hard-to-treat biofilms is an ever-increasing problem. These are communities of interspersed cells that are attached to one another on a surface, such as a catheter, or trapped into a cavity such as a paranasal sinus. Biofilms are difficult to detect, difficult to remove and intrinsically tolerant to most antifungal agents. These factors can lead to devastating consequences for the patient, including unnecessary morbidity and mortality, need for reoperations and prolonged hospital stay. This Review describes the breadth and growing impact fungal biofilms have on patient management and explains the mechanisms promoting biofilm formation, focusing on how targeting these can improve therapeutic options., Competing Interests: Competing interests: G.R. has received speaker fees from Gilead and Mundipharma. R.R.-R. has received speaker fees from Mundipharma, Astellas, Basilea, Gilead, Pfizer and Scynexis, and is the principal investigator for phase II clinical trials for Scynexis and F2G. The other authors do not declare any conflict of interest., (© 2025. Springer Nature Limited.)

Background: Between 26% and 52% of adults with intellectual disability experience urinary incontinence (UI). Little is known about the implications of urinary tract infections (UTIs) for this group. The aim was to screen for UTIs in a sample of adults with intellectual disability and UI., Method: Twenty adults with intellectual disability and UI recruited via community intellectual disability health care teams and provided a urine sample. Each sample was tested for the presence of UTI bacteria., Results: Half of the sample were found to have a possible or probable UTI. Nine adults had also been treated for a UTI within the previous 12 months; six adults had more than once., Conclusion: UTIs appear to be very common amongst adults with intellectual disability and UI, and careful attention to UTI symptoms, screening and treatment options for this group are recommended. Larger studies on UTI prevalence and associated factors are also warranted., Trial Registration: ClinicalTrials.gov: NCT05626062., (© 2024 The Author(s). Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs.

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2 + , triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in vivo patient-derived models of pancreatic ductal adenocarcinoma (PDAC) show reduced tissue viability and tumor volume with BP1003 and gemcitabine combination treatments. In addition to directly affecting tumor cells, BP1003 can modulate the tumor microenvironment. Unlike M1 differentiation, monocyte differentiation into anti-inflammatory M2 macrophages is suppressed by BP1003, indicating its potential contribution to immunotherapy. The broad anti-tumor effect of BP1003 in numerous preclinical solid tumor models, such as breast, ovarian, and pancreatic cancer models shown in this work, makes it a promising cancer therapeutic.

The WHO recently classified Candida auris as a fungal pathogen of "critical concern". Evidence suggests that C. auris emerged from the natural environment, yet the ability of this pathogenic yeast to survive in the natural environment is still poorly understood. The aim of this study, therefore, was to quantify the persistence of C. auris in simulated environmental matrices and explore the role of plastic pollution for facilitating survival and potential transfer of C. auris. Multi-drug resistant strains of C. auris persisted for over 30 days in river water or seawater, either planktonically, or in biofilms colonising high-density polyethylene (HDPE) or glass. C. auris could be transferred from plastic beads onto simulated beach sand, particularly when the sand was wet. Importantly, all C. auris cells recovered from plastics retained their pathogenicity; therefore, plastic pollution could play a significant role in the widescale environmental dissemination of this recently emerged pathogen., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clinically we have been aware of the concept of Candida biofilms for many decades, though perhaps without the formal designation. Just over 20 years ago the subject emerged on the back of progress made from the bacterial biofilms, and academic progress pace has continued to mirror the bacterial biofilm community, albeit at a decreased volume. It is apparent that Candida species have a considerable capacity to colonize surfaces and interfaces and form tenacious biofilm structures, either alone or in mixed species communities. From the oral cavity, to the respiratory and genitourinary tracts, wounds, or in and around a plethora of biomedical devices, the scope of these infections is vast. These are highly tolerant to antifungal therapies that has a measurable impact on clinical management. This review aims to provide a comprehensive overight of our current clinical understanding of where these biofilms cause infections, and we discuss existing and emerging antifungal therapies and strategies., (© 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Candia auris is an emerging human pathogenic yeast; yet, despite phenotypic attributes and genomic evidence suggesting that it probably emerged from a natural reservoir, we know nothing about the environmental phase of its life cycle and the transmission pathways associated with it. The thermotolerant characteristics of C. auris have been hypothesised to be an environmental adaptation to increasing temperatures due to global warming (which may have facilitated its ability to tolerate the mammalian thermal barrier that is considered a protective strategy for humans against colonisation by environmental fungi with pathogenic potential). Thus, C. auris may be the first human pathogenic fungus to have emerged as a result of climate change. In addition, the release of antifungal chemicals, such as azoles, into the environment (from both pharmaceutical and agricultural sources) is likely to be responsible for the environmental enrichment of resistant strains of C. auris; however, the survival and dissemination of C. auris in the natural environment is poorly understood. In this paper, we critically review the possible pathways through which C. auris can be introduced into the environment and evaluate the environmental characteristics that can influence its persistence and transmission in natural environments. Identifying potential environmental niches and reservoirs of C. auris and understanding its emergence against a backdrop of climate change and environmental pollution will be crucial for the development of effective epidemiological and environmental management responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Akinbobola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Candida albicans is the most prevalent and notorious of the Candida species involved in bloodstream infections, which is characterised by its capacity to form robust biofilms. Biofilm formation is an important clinical entity shown to be highly variable among clinical isolates. There are various environmental and physiological factors, including nutrient availability which influence the phenotype of Candida species. However, mechanisms underpinning adaptive biofilm heterogeneity have not yet been fully explored. Within this study we have profiled previously characterised and phenotypically distinct C. albicans bloodstream isolates. We assessed the dynamic susceptibility of these differing populations to antifungal treatments using population analysis profiling in addition to assessing biofilm formation and morphological changes. High throughput methodologies of RNA-Seq and LC-MS were employed to map and integrate the transcriptional and metabolic reprogramming undertaken by heterogenous C. albicans isolates in response to biofilm and hyphal inducing serum. We found a significant relationship between biofilm heterogeneity and azole resistance (P < 0.05). In addition, we observed that in response to serum our low biofilm forming (LBF) C. albicans exhibited a significant increase in biofilm formation and hyphal elongation. The transcriptional reprogramming of LBF strains compared to high biofilm forming (HBF) was distinct, indicating a high level of plasticity and variation in stress responses by heterogenous strains. The metabolic responses, although variable between LBF and HBF, shared many of the same responses to serum. Notably, a high upregulation of the arachidonic acid cascade, part of the COX pathway, was observed and this pathway was found to induce biofilm formation in LBF 3-fold. C. albicans is a highly heterogenous bloodstream pathogen with clinical isolates varying in antifungal tolerance and biofilm formation. In addition to this, C. albicans is capable of highly complex and variable regulation of transcription and metabolic pathways and heterogeneity across isolates further increases the complexity of these pathways. Here we have shown with a dual and integrated approach, the importance of studying a diverse panel of C. albicans isolates, which has the potential to reveal distinct pathways that can harnessed for drug discovery., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Ramage is an Editor for Biofilm. He has played no role in the review or editorial process for this article., (© 2023 The Authors.)

Bacterial vaginosis (BV) affects approximately 26% of women of childbearing age globally, presenting with 3-5 times increased risk of miscarriage and two-fold risk of pre-term birth . Antibiotics (metronidazole and clindamycin) are typically employed to treat BV; however the success rate is low due to the formation of recalcitrant polymicrobial biofilms. As a novel therapeutic, promising results have been obtained in vitro using Gardnerella endolysins, although to date their efficacy has only been demonstrated against simple biofilm models. In this study, a four-species biofilm was developed consisting of Gardnerella vaginalis, Fannyhessea vaginae, Prevotella bivia and Mobiluncus curtisii . Biofilms were grown in NYC III broth and treated using antibiotics and an anti- Gardnerella endolysin (CCB7.1) for 24 h. Biofilm composition, viability and structure were assessed using colony counts, live/dead qPCR and scanning electron microscopy. All species colonised biofilms to varying degrees, with G. vaginalis being the most abundant. Biofilm composition remained largely unchanged when challenged with escalated concentrations of conventional antibiotics. A Gardnerella- targeted endolysin candidate (CCB7.1) showed efficacy against several Gardnerella species planktonically, and significantly reduced viable G. vaginalis within polymicrobial biofilms at 1 to 4X pMIC (p < 0.05 vs. vehicle control). Collectively, this study highlights the resilience of biofilm-embedded pathogens against the currently used antibiotics and provides a polymicrobial model that allows for more effective pre-clinical screening of BV therapies. The Gardnerella -specific endolysin CCB7.1 demonstrated significant activity against G. vaginalis within polymicrobial biofilms, altering the overall community dynamic and composition., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew Cummings and David Corcorcan of CC Biotech Ltd have a patent for the clinical use of the endolysin(s) described in this study., (© 2023 The Authors.)

Biofilms formed by Candida species present a significant clinical problem due to the ineffectiveness of many conventional antifungal agents, in particular the azole class. We urgently require new and clinically approved antifungal agents quickly for treatment of critically ill patients. To improve efficiency in antifungal drug development, we utilized a library of 1280 biologically active molecules within the Tocriscreen 2.0 Micro library. Candida auris NCPF 8973 and Candida albicans SC5314 were initially screened for biofilm inhibitory activity using metabolic and biomass quantitative assessment methods, followed up by targeted evaluation of five selected hits. The initial screening (80% metabolic inhibition rate) revealed that there was 90 and 87 hits (approx. 7%) for C. albicans and C. auris, respectively. Additionally, all five compounds selected from the initial hits exhibited a biofilm inhibition effect against several key Candida species tested, including C. glabrata and C. krusei. Toyocamycin displayed the most potent activity at concentrations as low as 0.5 μg/mL, though was limited to inhibition. Darapladib demonstrated an efficacy for biofilm inhibition and treatment at a concentration range from 8 to 32 μg/mL and from 16 to 256 μg/mL, respectively. Combinational testing with conventional antifungals against C. albicans strains demonstrated a range of synergies for planktonic cells, and notably an anti-biofilm synergy for darapladib and caspofungin. Together, these data provide new insights into antifungal management possibilities for Candida biofilms., (© 2022 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.)

Candida auris can persistently colonize human skin, alongside a diverse bacterial microbiome. In this study we aimed to investigate the efficacy of antiseptic activities on dual-species interkingdom biofilms containing staphylococci to determine if antiseptic tolerance was negatively impacted by dual-species biofilms. Chlorhexidine, povidone iodine, and hydrogen peroxide (H 2 O 2 ), were able to significantly reduce biofilm viable cell counts following exposure at 2%, 10%, and 3%, respectively. Notably, H 2 O 2 -treated biofilms were able to significantly recover and considerably repopulate following treatment. Fortunately, inter-kingdom interactions in dual-species biofilms of C. auris and staphylococci did not increase the tolerance of C. auris against antiseptics in vitro. These data indicate mixed infections are manageable with chlorhexidine and povidone iodine, but caution should be exercised in the consideration of H 2 O 2 .

The opportunistic yeast Candida albicans and lactic acid bacteria Enterococcus faecalis are frequently co-isolated from various infection sites on the human body, suggesting a common interkingdom interaction. While some reports suggest an antagonism, the reason for their co-isolation therefore remains unclear. The purpose of this study was to undertake a detailed characterisation of this dual-species interaction. We used standard biofilm characterisation methodologies alongside an RNASeq analysis to assess the response of C. albicans to E. faecalis. We evaluated the relevance of pH to dual-species biofilm interactions and demonstrated that E. faecalis rapidly and significantly impacted C. albicans morphogenesis and biofilm formation, which was mirrored by levels of gene expression. These transcripts were enriched in amino acids biosynthesis and metabolism pathways in co-cultures, a finding that guided our investigation into pH related mechanism. We were able to demonstrate the direct role of E. faecalis induced low pH, which inhibited C. albicans hyphal morphogenesis and biofilm formation. The results suggest that the anti-candidal effect of E. faecalis is not based solely on a single mechanism, instead it may involve various mechanisms, which collectively reflects the complexity of interaction between C. albicans and E. faecalis and impacts treatment outcomes ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)