Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The N-terminal 175 residues are the ectodomain which lies outside the virus. This paper describes production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues including fusion peptide (FP) that binds to target cell membranes. The Fgp41 sequence was derived from one of the African clade A strains of HIV-1 which have been less studied than European/North American clade B strains. Fgp41 expression at ~100 mg/L culture was evidenced by an approach that included amino acid type 13CO and 15N labeling of recombinant protein and solid-state NMR (SSNMR) spectroscopy of lyophilized whole cells. The approach did not require any protein solubilization or purification and may be a general approach for detection of recombinant protein. The purified Fgp41 yield was ~5 mg/L culture. SSNMR spectra of membrane-associated Fgp41 showed high helicity at residues C-terminal of the FP. This was consistent with “six-helix bundle” (SHB) structure which is the final gp41 state during membrane fusion. This observation plus negligible Fgp41-induced vesicle fusion supported a function for SHB gp41 of membrane stabilization and fusion arrest. SSNMR spectra of residues in the membrane-associated FP evidenced a mixture of molecular populations with either helical or β sheet FP conformation. These and earlier SSNMR data strongly support the existence of these populations in the SHB state of membrane-associated gp41.

BackgroundBabesiosis is a parasitic vector-borne disease of increasing public health importance. Since the first human case was reported in 1957, zoonotic species have been reported on nearly every continent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in humans. Predicted climate change is expected to impact the spread of vectors, which is likely to affect the distribution of vector-borne diseases including human babesiosis.MethodsA scoping review has been executed to characterize the global evidence on zoonotic babesiosis. Articles were compiled through a comprehensive search of relevant bibliographic databases and targeted government websites. Two reviewers screened titles and abstracts for relevance and characterized full-text articles using a relevance screening and data characterization tool developed a priori.ResultsThis review included 1394 articles relevant to human babesiosis and/or zoonotic Babesia species. The main zoonotic species were B. microti, B. divergens, B. duncani and B. venatorum. Articles described a variety of study designs used to study babesiosis in humans and/or zoonotic Babesia species in vectors, animal hosts, and in vitro cell cultures. Topics of study included: pathogenesis (680 articles), epidemiology (480), parasite characterization (243), diagnostic test accuracy (98), mitigation (94), treatment (65), transmission (54), surveillance (29), economic analysis (7), and societal knowledge (1). No articles reported predictive models investigating the impact of climate change on Babesia species.ConclusionKnowledge gaps in the current evidence include research on the economic burden associated with babesiosis, societal knowledge studies, surveillance of Babesia species in vectors and animal hosts, and predictive models on the impact of climate change. The scoping review results describe the current knowledge and knowledge gaps on zoonotic Babesia which can be used to inform future policy and decision making.

COVID-19 research has been produced at an unprecedented rate and managing what is currently known is in part being accomplished through synthesis research. Here we evaluated how the need to rapidly produce syntheses has impacted the quality of the synthesis research. Thus, we sought to identify, evaluate and map the synthesis research on COVID-19 published up to 10 July 2020. A COVID-19 literature database was created using pre-specified COVID-19 search algorithms carried out in eight databases. We identified 863 citations considered to be synthesis research for evaluation in this project. Four-hundred and thirty-nine reviews were fully assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) and rated as very low-quality (n = 145), low-quality (n = 80), medium-quality (n = 208) and high-quality (n = 151). The quality of these reviews fell short of what is expected for synthesis research with key domains being left out of the typical methodology. The increase in risk of bias due to non-adherence to systematic review methodology is unknown and prevents the reader from assessing the validity of the review. The responsibility to assure the quality is held by both producers and publishers of synthesis research and our findings indicate there is a need to equip readers with the expertise to evaluate the review conduct before using it for decision-making purposes.

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Antimicrobial-resistant (AMR) bacteria are a threat to public health as they can resist treatment and pass along genetic material that allows other bacteria to become drug-resistant. To assess foodborne AMR risk, the Codex Guidelines for Risk Analysis of Foodborne AMR provide a framework for risk profiles and risk assessments. Several elements of a risk profile may benefit from a scoping review. To contribute to a larger risk profile structured according to the Codex Guidelines, our objective was to conduct a scoping review of the current state of knowledge on the distribution, frequency and concentrations of extended-spectrum β-lactamase (ESBL)producing Enterobacteriaceae in salmon and shrimp. Articles were identified via a comprehensive search of five bibliographic databases. Two reviewers screened titles and abstracts for relevance and characterized full-text articles with screening forms developed a priori. Sixteen relevant studies were identified. This review found that there is a lack of Canadian data regarding ESBL-producing Enterobacteriaceae in salmon and shrimp. However, ESBL-producing Escherichia coli, Klebsiella pneumoniae, and other Enterobacteriaceae have been isolated in multiple regions with a history of exporting seafood to Canada. The literature described herein will support future decision-making on this issue as research/surveillance and subsequent assessments are currently lacking.

Campylobacter spp. are one of the most common causes of bacterial gastroenteritis in Canada and worldwide. Fluoroquinolones are often used to treat complicated human campylobacteriosis and strains of Campylobacter spp. resistant to these drugs are emerging along the food chain. A scoping review was conducted to summarize how human (fluoro)quinolone-resistant (FQR; quinolones including fluoroquinolones) Campylobacter spp. infections are characterized in the literature by describing how burden of illness (BOI) associated with FQR is measured and reported, describing the variability in reporting of study characteristics, and providing a narrative review of literature that compare BOI measures of FQR Campylobacter spp. infections to those with susceptible infections. The review identified 26 studies that yielded many case reports, a lack of recent literature, and a lack of Canadian data.Studies reported 26 different BOI measures and the most common were hospitalization, diarrhea, fever, and duration of illness. There were mixed results as BOI measures reported in literature were inconsistently defined and there were limited comparisons between resistant and susceptible infections. This presents a challenge when attempting to assess the magnitude of the BOI due to FQR Campylobacter spp., highlighting the need for more research in this area.

Resistance to carbapenems in human pathogens is a growing clinical and public health concern. The carbapenems are in an antimicrobial class considered last-resort, they are used to treat human infections caused by multidrug-resistant Enterobacterales, and they are classified by the World Health Organization as 'High Priority Critically Important Antimicrobials'. The presence of carbapenem-resistant Enterobacterales (CREs) of animal-origin is of concern because targeted studies of Canadian retail seafood revealed the presence of carbapenem resistance in a small number of Enterobacterales isolates. To further investigate this issue, a risk profile was developed examining shrimp and salmon, the two most important seafood commodities consumed by Canadians and E. coli, a member of the Enterobacterales order.Carbapenem-resistant E. coli (CREc) isolates have been identified in shrimp and other seafood products. Although carbapenem use in aquaculture has not been reported, several classes of antimicrobials are utilized globally and co-selection of antimicrobial-resistant microorganisms in an aquaculture setting is also of concern. CREs have been identified in retail seafood purchased in Canada and are currently thought to be uncommon. However, data concerning CRE or CREc occurrence and distribution in seafood is limited, and argue for implementation of ongoing or periodic surveillance.