Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic homeostasis that is highly conserved in evolution. Recent evidence has revealed the existence of a complex interplay between mTOR signalling and immunity. We review here the emerging role of mTOR signalling in the regulation of Toll-like receptor-dependent innate responses and in the activation of T cells and antigen-presenting cells. We also highlight the importance of amino-acid starvation-driven mTOR inhibition in the control of autophagy and intracellular bacterial clearance.
We present a case of Bartonella quintana infective endocarditis requiring valvular surgery in an Indigenous patient from northern Alberta that was identified months after initial presentation to hospital with undifferentiated laboratory abnormalities. Syndromes caused by B. quintana are often challenging to diagnose due to their non-specific presentation and the difficulty in detecting this organism using traditional culture methods. Additionally, risk factors for B. quintana include marginal housing and alcohol use disorder, which often impede access to health care. Indigenous patients in northern Canada often face worse health outcomes compared with other regions owing to poor economic conditions, substandard housing, and limited access to health care resources. Given that risk factors for B. quintana are prevalent throughout northern Canada and that this infection is difficult to diagnose, we surmise that the prevalence of B. quintana infection is underestimated in northern Canada.
Objective: To analyze the spread of a novel sequence type (ST1478) of vancomycin-resistant Enterococcus faecium across Canadian hospitals. Design: Retrospective chart review of patients identified as having ST1478 VRE bloodstream infection. Setting: Canadian hospitals that participate in the Canadian Nosocomial Infection Surveillance Program (CNISP). Methods: From 2013 to 2018, VRE bloodstream isolates collected from participating CNISP hospitals were sent to the National Microbiology Laboratory (NML). ST1478 isolates were identified using multilocus sequence typing, and whole-genome sequencing was performed. Patient characteristics and location data were collected for patients with ST1478 bloodstream infection (BSI). The sequence and patient location information were used to generate clusters of infections and assess for intrahospital and interhospital spread. Results: ST1478 VRE BSI occurred predominantly in a small number of hospitals in central and western Canada. Within these hospitals, infections were clustered on certain wards, and isolates often had <20 single-nucleotide variants (SNV) differences from one another, suggesting a large component of intrahospital spread. Furthermore, some patients with bloodstream infections were identified as moving from one hospital to another, potentially having led to interhospital spread. Genomic analysis of all isolates revealed close relatedness between isolates at multiple different hospitals (<20 SNV) not predicted from our epidemiologic data. Conclusions: Both intrahospital and regional interhospital spread have contributed to the emergence of VRE ST1478 infections across Canada. Whole-genome sequencing provides evidence of spread that might be missed with epidemiologic investigation alone.
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