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Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter. Author summary: Intravascular catheters are widely used to administer medication and provide nutritional support to patients. However, their clinical use also increases the incidence of bloodstream infections and constitutes a risk factor for Candida albicans infection. Microbial biofilms have been proposed as the primary living style of microbes on a surface, including those on intravascular catheters. Numerous studies focus on identifying microbial factors contributing to C. albicans biofilm formation. However, our understanding of the host factors involved in controlling C. albicans biofilms on the surface of intravascular catheters is limited. In this study, we demonstrated that the biofilms in intravascular catheters removed from candidiasis patients comprised not only C. albicans cells but also human immune cells. Among these catheters, the immune cells interacting with the fungus exhibited different properties of NETosis, a type of neutrophil cell death with antimicrobial activity. We further showed that the catheter isolates exhibited reduced expression of candidalysin. Supplementation of candidalysin promoted NETosis induced by C. albicans biofilms and diminished C. albicans biofilms on a surface. Our findings highlight the implication of neutrophils in eliminating C. albicans biofilms, and point out the benefit of reduced candidalysin expression for C. albicans to persist in intravascular catheters. [ABSTRACT FROM AUTHOR]

Objectives The global prevalence of vancomycin-resistant Enterococcus faecium (VREfm) highlights the need for new anti-enterococcal agents. Here, we assessed the molecular epidemiology of clinical VREfm bacteraemic isolates from a medical centre in northern Taiwan in 2019–2020 and to evaluate their susceptibility to last-line antibiotics and a new antimicrobial agent, SC5005. Methods The molecular epidemiology of VREfm was investigated using van genotyping, MLST and PFGE. The susceptibilities of VREfm strains to antibiotics and SC5005 were determined using the agar dilution and broth microdilution methods. The capability of E. faecium to develop resistance to antibiotics and SC5005 was evaluated using frequency of resistance and multipassage resistance assays. The mode of action of SC5005 was assessed by time-kill, bacterial membrane integrity and membrane potential assays. Results All 262 VREfm isolates harboured vanA gene, and the most prevalent sequence type was ST17 (51%, n  = 134, 84 pulsotypes), followed by ST78 (25%, n  = 65, 54 pulsotypes). Additionally, we identified four new STs (ST2101, ST2102, ST2135 and ST2136) and observed the arrival of multidrug-resistant ST1885 in Taiwan. Moreover, SC5005 was effective against all VREfm isolates, including those non-susceptible to last-line antibiotics. SC5005 can disrupt and depolarize the bacterial membrane to kill E. faecium without detectable resistance. Conclusions The findings provide insights into the latest epidemiology and resistance profiles of bacteraemic-causing VREfm in northern Taiwan. Additionally, SC5005 has the potential for development as a new therapeutic to treat VREfm infections. [ABSTRACT FROM AUTHOR]