Clostridioides difficile infection and One Health: an equine perspective.

Clostridioides (Clostridium) difficile presents a significant health risk to humans and animals. The complexity of the bacterial-host interaction affecting pathogenesis and disease development creates an ongoing challenge for epidemiological studies, control strategies and prevention planning. The recent emergence of human disease caused by strains of C. difficile found in animals adds to mounting evidence that C. difficile infection (CDI) may be a zoonosis. In equine populations, C. difficile is a known cause of diarrhoea and gastrointestinal inflammation, with considerable mortality and morbidity. This has a significant impact on both the well-being of the animal and, in the case of performance and production animals, it may have an adverse economic impact on relevant industries. While C. difficile is regularly isolated from horses, many questions remain regarding the impact of asymptomatic carriage as well as optimization of diagnosis, testing and treatment. This review provides an overview of our understanding of equine CDI while also identifying knowledge gaps and the need for a holistic One Health approach to a complicated issue.

Exploratory Investigation of Personal Influences on Educators' Engagement in Engineering Ethics and Societal Impacts Instruction.

Cultivating an understanding of ethical responsibilities and the societal impacts of technology is increasingly recognized as an important component in undergraduate engineering curricula. There is growing research on how ethics-related topics are taught and outcomes are attained, especially in the context of accreditation criteria. However, there is a lack of theoretical and empirical understanding of the role that educators play in ethics and societal impacts (ESI) instruction and the factors that motivate and shape their inclusion of this subject in the courses they teach and co-curricular activities they mentor. The goal of this research was to explore the role of faculty's personal influences on their inclusion of ESI instruction in these settings. Personal influences are distinguished from external or environmental drivers such as teaching assignments, university policies, and department curriculum decisions. This research employed a grounded theory methodology and extracted data from interviews with 19 educators who teach ESI to engineering students to develop an emergent conceptualization of personal influences. Four categorie were identified: intrapersonal (drawing on self-interests and beliefs), interpersonal (drawing on relationships to engage in the intersectional field of ESI), academic (using their experiences as a student), and professional (leveraging non-academic work to understand the application of ESI and bring ESI into the classroom). The findings suggested a wide range of entry points (based on varying interests, beliefs, interactions, and backgrounds) into ESI instruction for faculty members who do not currently teach ESI and for those looking to expand the inclusion of ESI in their courses. Based on these findings, departments and administrators are encouraged to foster educators' agency, support access to professional development and engagement, facilitate interdisciplinary collaboration, and broaden hiring decisions to account for the impact of educators' holistic identity on their instruction.

Cationic biaryl 1,2,3-triazolyl peptidomimetic amphiphiles targeting Clostridioides (Clostridium) difficile: Synthesis, antibacterial evaluation and an in vivo C. difficile infection model.

Clostridioides (formerly Clostridium) difficile is a Gram-positive anaerobic bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are vastly inadequate, expensive and limited; this results in an exorbitant medical and financial burden. New, inexpensive chemotherapeutic treatments for C. difficile infection with improved efficacy are urgently needed. A streamlined synthetic pathway was developed to allow access to 38 novel mono- and di-cationic biaryl 1,2,3-triazolyl peptidomimetics with increased synthetic efficiency, aqueous solubility and enhanced antibacterial efficacy. The monocationic arginine derivative 28 was identified as a potent, Gram-positive selective antibacterial with MIC values of 4 µg/mL against methicillin-resistant Staphylococcus aureus and 8 µg/mL against C. difficile. Furthermore, the dicationic bis-triazole analogue 50 was found to exhibit broad-spectrum activity with substantial Gram-negative efficacy against Acinetobacter baumannii (8 µg/mL), Pseudomonas aeruginosa (8 µg/mL) and Klebsiella pneumoniae (16 µg/mL); additionally, compound 50 displayed reduced haemolytic activity (<13%) in an in vitro haemolysis assay. Membrane-disruption assays were conducted on selected derivatives to confirm the membrane-active mechanism of action inherent to the synthesized amphiphilic compounds. A comparative solubility assay was developed and utilized to optimize the aqueous solubility of the compounds for in vivo studies. The biaryl peptidomimetics 28 and 67 were found to exhibit significant efficacy in an in vivo murine model of C. difficile infection by reducing the severity and slowing the onset of disease.

Evaluation of reduced susceptibility to quaternary ammonium compounds and bisbiguanides in clinical isolates and laboratory-generated mutants of Staphylococcus aureus.

The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.