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Candida auris is an emerging yeast that is associated with antifungal resistance and healthcare-associated outbreaks. From 2012 to 2019, there were 24 known cases of C. auris colonization or infection in Canada. Isolates were from axilla/groin (n = 6), ear (n = 5), blood (n = 4), toe (n = 2), and a variety of other sites (n = 7). Canadian isolates belonged to the four main genomic clades: Clade I (formerly called South Asian clade, n = 12), Clade II (East Asian, n = 3), Clade III (African, n = 4), and Clade IV (South American, n = 5). Isolates within each clade were clonal; however, whole genome sequencing may be helpful in identifying clusters within healthcare facilities. Lay summary The fungal pathogen Candida auris has caused many hospital outbreaks and is often multidrug resistant. All four major strains of C. auris were identified in Canada from 2012 to 2019. Genomic epidemiology may be useful for identifying and reducing transmission of C. auris within hospitals.

Background There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. Methods This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. Interpretation The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

Lipopolysaccharide (LPS) may accumulate inside mammalian cells through endocytotic uptake or during the replication in invasive bacterial strains. However, the effects of intracellular LPS on cell function remain unknown. This study therefore examined the action of intracellularly applied E. coli LPS on large-conductance, Ca2+-dependent K+ channels (BK channels) in the membrane of rat cerebrovascular smooth muscle cells (CVSMCs). LPS (10-100 microg/ml) rapidly increased the open probability of BK channels when applied to the cytoplasmic face of CVSMC membrane patches. This response was reversible, dose-dependent and reflected an enhanced rate of channel opening in the presence of LPS. These results show for the first time that LPS can alter the gating behavior of ionic channels when applied to the cytoplasmic face of a eukaryotic cell membrane.

Clostridium difficile is the most common cause of antibiotic-associated diarrhea, and it occasionally causes extraintestinal infections. We present a case of C. difficile-associated diarrhea that led to vertebral osteomyelitis associated with hardware. The osteomyelitis became symptomatic 2 years after the initial diarrheal event. C. difficile recovered from internal hardware sites cannot simply be regarded as a contaminant but should be treated.

Patch-clamp recordings were used to study the effects of Escherichia coli bacterial endotoxin (lipopolysaccharide, LPS) on the properties of large-conductance, Ca 2+ -dependent K + channels (BK channels) in the membrane of enzymatically dispersed rat cerebrovascular smooth muscle cells (CVSMCs). LPS had negligible effects on the kinetic and conductance properties of BK channels when applied to the extracellular domain of these channels. However, acute application of LPS (10–100 μg/ml) to inside-out patches of CVSMC membrane isolated in a cell-free environment rapidly and reversibly increased the open probability of BK channels, leaving the conductance of these channels unaltered. The magnitude of this effect decreased as the concentration of free Ca 2+ at the cytoplasmic membrane face was lowered, but was little affected by changes in membrane potential. Kinetic analysis showed that LPS accelerated reopening of BK channels while having little effect on mean channel open time. Detoxified E. coli LPS, from which the fatty acid chains of Lipid A were partially removed, showed slightly reduced activity when compared to the parent endotoxin molecule. A purified E. coli Lipid A had negligible effects on BK channel function. These results indicate that LPS activates BK channels in cerebrovascular smooth muscle cells when present at the cytoplasmic membrane face. This novel mechanism may provide insights into the regulation of BK channels by intracellular, membrane-associated elements.