Candida auris is an emerging multidrug-resistant pathogen designated by the World Health Organization as a critical priority due to its persistence, transmissibility, and association with healthcare outbreaks. Despite its clinical significance, the contribution of phenotypic heterogeneity to pathogenicity and treatment response remains poorly understood. In this study, we identified dual white (W) and pink (P) morphotypes in seven of 278 clinical isolates screened on CHROMagar™ Candida Plus and characterized their genetic relatedness, antifungal susceptibility, and phenotypic switching behavior. Whole-genome sequencing and internal transcribed spacer (ITS) analyses confirmed that paired morphotypes were clonally related (0–57 SNPs divergence) and belonged to Clade I, indicating within-host diversification rather than co-infection with distinct strains. All isolates carried identical ERG11 Y132F mutations and wild-type FKS1 sequences across both morphotypes, demonstrating that morphotype variation occurs independently of primary antifungal resistance determinants. Phenotypic profiling demonstrated comparable resistance profiles and aggregation capacity between paired morphotypes, with pseudohyphal formation as the principal differential trait. Systematic switching analysis across CHROMagar, yeast peptone dextrose (YPD), and sabouraud dextrose agar (SDA) under multiple temperature and population conditions identified three principal patterns: interaction-dependent switching, in which mixed subpopulations generated enhanced or novel phenotypes not reproduced in pure cultures; morphotype-driven switching, dominated by a single subpopulation; and intrinsic switching capacity retained independently by both morphotypes. Switching dynamics were strongly modulated by temperature, growth medium, and incubation duration. These findings establish phenotypic switching in C. auris as a dynamic, environmentally modulated process driven in part by intercellular interactions within clonal populations. This plasticity may contribute to persistence and virulence without altering antifungal resistance profiles, underscoring the need to recognize and separately evaluate distinct C. auris morphotypes for antifungal susceptibility, particularly in persistent or treatment-refractory infections.
The clinical significance of transient Borrelia burgdorferi sensu lato complex (hereafter referred to as B. burgdorferi) spirochetemia remains poorly understood and has rarely been documented. We report the isolation of viable B. garinii genospecies from the blood of a previously healthy child presenting with a Streptococcus anginosus group (SAG) brain abscess. An eight-year-old girl presented with four days of headache, fever, nausea, slightly reduced general condition, and mild facial asymmetry. Initial evaluation, including lumbar puncture, raised suspicion of viral meningitis or Lyme neuroborreliosis (LNB). Based on the differential diagnosis of Lyme disease, she was enrolled in the prospective BRILLIANT study (NCT06045416), with additional blood and cerebrospinal fluid (CSF) sampling for B. burgdorferi culture and serology. Following initial outpatient management, she re-presented with clinical deterioration and signs of raised intracranial pressure. Cranial magnetic resonance imaging revealed a brain abscess requiring surgical drainage. Abscess cultures yielded SAG. Dental treatment four days before symptom onset provided a plausible source of infectious spread. Treatment with intravenous ceftriaxone and metronidazole for six weeks resulted in complete clinical recovery and radiological improvement. Borrelia burgdorferi-specific two-tier serology and CSF culture remained negative. In contrast, blood plasma culture for B. burgdorferi obtained at initial presentation yielded viable spirochetes after seven weeks. Borrelia burgdorferi DNA was confirmed by flaB-targeted qPCR, and hybrid whole-genome sequencing generated a near-complete genome identifying B. garinii genospecies. This case demonstrates viable B. garinii spirochetemia without serological evidence of LNB, incidentally detected during investigation of a SAG brain abscess. It highlights the uncertain clinical significance of transient B. burgdorferi spirochetemia, and the importance of interpreting microbiological findings within the clinical context.
The emergence and rapid spread of multidrug resistance in Plasmodium parasites, particularly in the Greater Mekong region and increasingly in Sub-Saharan Africa. Resistance has led to an urgent need to develop novel anti-malaria therapies with an effective mechanism. Several non-classical targets, including Na++ pump PfATP4 (Plasmodium falciparum ATPase 4), PI4K (Phosphatidylinositol 4-kinase) and PfNCR1(Plasmodium falciparum Niemann-Pick Type C1-Related protein), are highly active against the asexual stage of Plasmodium. We summarise the progress achieved on key emerging targets over past decade and emerging pipeline of artemisinin-combination therapies (ACTs). Other targets, such as dihydroorotate dehydrogenase (PfDHODH) for pyrimidine biosynthesis, ion transporters, mitochondrial electron transport chain, and apicoplast metabolic pathways, have demonstrated significant therapeutic potential due to their essential roles in parasite physiology and minimal homology to human counterparts. Combating drug-resistant malaria parasites and strengthening the global antimalarial drug pipeline for long-term disease control can be achieved by developing new ways to target parasites. This comprehensive review discusses the current status of novel antimalarial drug targets, recent discoveries and future of novel therapies in the following innovation areas: Protein synthesis machinery as drug targets, hemoglobin metabolism targets, transport proteins therapeutic targets, Kinase targets, Organelles and cell targets, and mitochondrial targets, which fill critical gaps in the existing therapeutic arsenal.
Community-acquired Clostridioides difficile infection (CA-CDI) is increasingly recognized outside healthcare settings, yet the contribution of dental antibiotic prescribing remains poorly characterized. This study compared patients with CA-CDI following antibiotics prescribed by dental practitioners versus family physicians. We conducted a retrospective cohort study at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Zagreb, Croatia, including adults with a first episode of confirmed CA-CDI following outpatient antibiotic exposure between 2011 and 2019. Characteristics were compared by prescriber. Among 666 patients with CA-CDI, 190 (28.5
