Epidemiology and antimicrobial resistance profiles of pathogenic Escherichia coli from commercial swine and poultry abattoirs and farms in South Africa : a One Health approach

DATA AVAILABILITY : The data presented in this study are included in the article and supplementary material. Additional information can be requested from the corresponding author.Pathogenic Escherichia coli (PEC) are important foodborne bacteria that can cause severe illness in humans. The PECs thrive within the intestines of humans as well as animals and may contaminate multiple ecosystems, including food and water, via faecal transmission. Abattoir and farm employees are at high risk of PEC exposure, which could translate to community risk through person-to-person contact. To determine the epidemiology and resistome of PECs in Gauteng and Limpopo provinces of South Africa, 198 swine faecal samples, 220 poultry cloacal swabs, 108 human hand swabs, 11 run-off water samples from abattoirs and farms were collected from four swine and five poultry commercial abattoirs and two swine farms. One effluent sample each was collected from four wastewater treatment plants (WWTP) and a tertiary hospital setting. Phenotypic and genotypic techniques were used including polymerase chain reaction, pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Results showed EHEC and EPEC prevalence was 4.1 % (22/542) and 20.8 % (113/542), respectively, with the O26 serogroup detected the most in PEC isolates. According to the PFGE dendrogram, isolates from poultry, human hand swabs and run-off water clustered together. Diverse virulence factors such as the novel stx2k subtype and eae genes were detected among the 36 representative PEC isolates according to WGS. The results showed that 66.7 % (24/36) of sequenced PECs presented with multi-drug resistance (MDR) to β-lactamase 13.9 % (5/36), aminoglycoside 61.1 % (22/36), tetracycline 41.7 % (15/36) and quinolones 38.9 % (14/36). No colistin nor carbapenem resistance was detected. Sequence types (STs) associated with MDR in this study were: ST752, ST189, ST206, ST10, ST48 and ST38. The findings highlight the threat of zoonotic pathogens to close human contacts and the need for enhanced surveillance to mitigate the spread of MDR foodborne PECs.The National Health Laboratory Service Trust, the University of Pretoria and the National Research Foundation. Whole genome sequencing was made possible by support from the SEQAFRICA project which is funded by the Department of Health and Social Care's Fleming Fund using UK aid.https://www.elsevier.com/locate/scitotenvhj2024Medical MicrobiologyVeterinary Tropical DiseasesSDG-02:Zero HungerSDG-03:Good heatlh and well-beingSDG-06:Clean water and sanitatio

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry

Objectives Digital ulcers (DUs) occur in up to half of patients with systemic sclerosis (SSc) and may lead to infection, gangrene and amputation with functional disability and reduced quality of life. This study has elucidated the burden of SSc-associated DUs through identification of four patient categories based on the pattern of DU recurrence over a 2-year observation period.Methods Patients with SSc-associated DUs enrolled in the Digital Ulcers Outcome Registry between 1 April 2008 and 19 November 2013, and with 2years of observation and 3 follow-up visits during the observation period were analysed. Incident DU-associated complications were recorded during follow-up. Work and daily activity impairment were measured using a functional assessment questionnaire completed by patients after the observation period. Potential factors that could predict incident complications were identified in patients with chronic DUs.Results From 1459 patients, four DU occurrence categories were identified: 33.2% no-DU; 9.4% episodic; 46.2% recurrent; 11.2% chronic. During the observation period, patients from the chronic category had the highest rate of incident complications, highest work impairment and greatest need for help compared with the other categories. Independent factors associated with incident complications included gastrointestinal manifestations (OR 3.73, p=0.03) and previous soft tissue infection (OR 5.86, p=0.01).Conclusions This proposed novel categorisation of patients with SSc-associated DUs based on the occurrence of DUs over time may help to identify patients in the clinic with a heavier DU burden who could benefit from more complex management to improve their functioning and quality of life

Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology

Solute carriers form one of three major superfamilies of membrane transporters in humans, and include uniporters, exchangers and symporters. Following several decades of molecular characterisation, multiple solute carriers that form obligatory heteromers with unrelated subunits are emerging as a distinctive principle of membrane transporter assembly. Here we comprehensively review experimentally established heteromeric solute carriers: SLC3-SLC7 amino acid exchangers, SLC16 monocarboxylate/H+ symporters and basigin/embigin, SLC4A1 (AE1) and glycophorin A exchanger, SLC51 heteromer Ost α-Ost β uniporter, and SLC6 heteromeric symporters. The review covers the history of the heteromer discovery, transporter physiology, structure, disease associations and pharmacology - all with a focus on the heteromeric assembly. The cellular locations, requirements for complex formation, and the functional role of dimerization are extensively detailed, including analysis of the first complete heteromer structures, the SLC7-SLC3 family transporters LAT1-4F2hc, b0,+AT-rBAT and the SLC6 family heteromer B0AT1-ACE2. We present a systematic analysis of the structural and functional aspects of heteromeric solute carriers and conclude with common principles of their functional roles and structural architecture