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An expanding fish stock offers a rare opportunity to support fishing enterprises whose traditional fisheries have diminished or failed. The Eastern Nova Scotia snow crab fishery is one example, where in 2005, a growing stock allowed benefit-sharing among more than 700 harvesters. As a contributing case study of social and institutional aspects of sustainability, we review the background of that fishery and the outcomes of the redistribution of fishery benefits. Based on more than 50 semistructured interviews, the case study demonstrates how conflict has settled into cooperation, with the fishery remaining biologically sound and highly beneficial to individuals and their communities. However, the method chosen to manage the distribution in Eastern Nova Scotia has not guaranteed that benefits will remain in local communities. In other jurisdictions, alternative approaches developed in conjunction with broad-based harvester organizations demonstrate better benefit retention in local communities. When compared with the Canada Fisheries Research Network Sustainability Framework, this case study offers insights into the benefits that thoughtful resource redistribution can provide, illustrating that fishery policy decisions must anticipate long-term implications and should apply a definition of fisheries sustainability that includes community well-being, in this case, as evidenced in local licence retention. [ABSTRACT FROM AUTHOR]

Objectives To investigate the genomic diversity and β-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). Methods We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic–pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. Results Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. Conclusions We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated. [ABSTRACT FROM AUTHOR]

Ceftazidime–avibactam resistance among carbapenem-resistant Klebsiella pneumoniae at our hospital has emerged in sequence type (ST)-258, clade II isolates. We investigated hypermutability of ST258, clade II (n = 6) and clade I K. pneumoniae (n = 8) using a standard rifampin assay. Mutational frequencies were ≤10–7.1, indicating that isolates were not hypermutators. Mutational frequencies did not differ between clade II and I isolates. Ceftazidime–avibactam resistance among ST258, clade II K. pneumoniae is most likely a reflection of our hospital's ecology. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. Materials and methods Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. Results Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. Conclusions Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains. [ABSTRACT FROM AUTHOR]

Background IAC is a common manifestation of invasive candidiasis, but its pathogenesis is poorly understood. We developed a mouse model of C. albicans IAC, in which disease progresses from peritonitis to abscesses (IAA) in a manner that recapitulates human infection. Our goal was to use the model to identify C. albicans TFs that regulate virulence during IAC. Methods We screened a signature-tagged library (48 unique oligonucleotide markers) of homozygous deletion mutants for 165 C. albicans TF genes, created in duplicate in strain SC5314 (S. Noble). Mice were infected intra-peritoneally in triplicate with pools of 24 mutants and wild-type, and strains harvested at 72 hours in IAA. Results Twenty-one TF mutants were significantly attenuated for virulence in both libraries, and 2 TF mutants were significantly more virulent in both libraries, as measured by tissue burdens (figure). Biologic processes over-represented among attenuated mutants were regulation of pH responses, biofilm, hyphal formation, echinocandin responses, and copper metabolism. pH responses are likely to be crucial to pathogenesis of IAC, as C. albicans transitions from pH 8 during peritonitis to pH 6.8 within IAA. 9 pH response regulators contributing to virulence included RIM101, STP2 (alkaline), ASH1, SFL1, SFL2 (neutral), MNL1, SKO1, PHO4 (weak acid), and CSR1 (acid). We created rim101 null mutant and reconstitution strains, and demonstrated that the gene was essential for complete virulence during peritonitis and IAA. Transcriptional profiling of strains by RT-PCR during peritonitis and in vitro showed both conserved and rewired Rim101 targets. SAP5, which encodes an aspartyl protease, is a major Rim101 target in vivo and in vitro ; over-expression of SAP5 in rim101 restored virulence during IAA at 3, 7, and 10 days, but not during peritonitis. Other pH regulatory TF genes are currently being validated as virulence determinants, and pathway relationships between MNL1, SKO1, and PHO4 during IAA formation are being explored through epistasis approaches. Conclusion Screening of a C. albicans TF mutant library identified pH responses and other biologic processes as important during pathogenesis of IAC. Rim101, an alkaline pH response regulator, contributes to both peritonitis and IAA, the latter at least in part through its effects on Sap5. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

An interdisciplinary team of academics and representatives of fishing fleets and government collaborated to study the emerging requirements for sustainability in Canada's fisheries. Fisheries assessment and management has focused on biological productivity with insufficient consideration of social (including cultural), economic, and institutional (governance) aspects. Further, there has been little discussion or formal evaluation of the effectiveness of fisheries management. The team of over 50 people (i) identified a comprehensive set of management objectives for a sustainable fishery system based on Canadian policy statements, (ii) combined objectives into an operational framework with relevant performance indicators for use in management planning, and (iii) undertook case studies that investigated some social, economic, and governance aspects in greater detail. The resulting framework extends the suite of widely accepted ecological aspects (productivity and trophic structure, biodiversity, and habitat–ecosystem integrity) to include comparable economic (viability and prosperity, sustainable livelihoods, distribution of access and benefits, regional–community benefits), social (health and well-being, sustainable communities, ethical fisheries), and institutional (legal obligations, good governance structure, effective decision-making) aspects of sustainability. This work provides a practical framework for implementation of a comprehensive approach to sustainability in Canadian fisheries. The project also demonstrates the value of co-construction of collaborative research and co-production of knowledge that combines and builds on the strengths of academics, industry, and government. [ABSTRACT FROM AUTHOR]

In 2010, more than 20 associations representing harvesters from five provinces bordering the range of American lobster ( Homarus americanus) in Canada, from the Gulf of Maine to southern Labrador, joined government research scientists at Fisheries and Oceans Canada (and one provincial department) and researchers from Canadian universities (two English- and four French-speaking) to establish the Lobster Node. This partnership was formed to address knowledge gaps on lobster productivity, stock structure, and connectivity through collaborative research under the auspices of the Canadian Fisheries Research Network (CFRN), which was funded by the Natural Sciences and Engineering Research Council of Canada. In so doing, the research partners overcame barriers of geography, language, culture, education, and, in some cases, longstanding disputes around management and conservation measures. This paper reviews why and how the Lobster Node was formed, what it achieved scientifically, what benefits (and challenges) it provided to the partners, and why it succeeded. It concludes by advocating for the creation of a permanent collaborative platform to conduct research in support of lobster fisheries in Canada. [ABSTRACT FROM AUTHOR]

Background The majority of bacterial BSIs are believed to stem from a single, clonal organism. We hypothesized that most CRK BSIs are caused by genetically diverse, clonal strains that exhibit different phenotypes. Methods Blood cultures (BCs) that were positive for CRK from each of 10 patients (patients) were streaked onto agar plates, and 100 individual colonies were chosen for Illumina whole-genome sequencing. Strains from 3 patients were tested for in vitro phenotypes and virulence in mice. Results Patients had BSIs due to ST258 K. pneumoniae (Kp; 6), non-ST258 Kp (3), and K. michiganensis (Km; 1). 5 patients were infected with strains that differed by core genome single nucleotide polymorphism phylogeny (2–5 unique genotypes/patient) [figure]. 6 patients were infected with strains that differed by gene or plasmid content, and/or gene deletions [table]. Differences in individual patients encompassed antibiotic resistance and putative virulence genes (including mixtures of blaKPC+ and blaKPC– strains, and various capsular (CPS) and porin mutant strains). In total, BSIs in 8 of 10 patients were caused by a genotypically diverse population. In each of 3 patients, genotypically diverse ST258 Kp strains demonstrated significant differences in antibiotic susceptibility, CPS content, mucoviscosity, adherence, resistance to serum killing, and mortality rates and tissue burdens during BSIs of mice. ST258 strains from a pt with and without a KPC-bearing IncFIA plasmid differed in β-lactam susceptibility, but were equally virulent. Progressive loss of CPS in ST258 strains from another patient enhanced serum killing and adherence, and attenuated virulence. Using PCR markers to test 96 colonies per positive BC bottle, we demonstrated that strains selected by the clinical micro lab accounted for 2% to 98% of a population in different patients. Conclusion CRK causing BSIs in most patients demonstrated remarkable genotypic diversity, which impacted antibiotic susceptibility, virulence and other phenotypes. Differences were not recognized during hospitalization since clinical labs select single, morphologically distinct colonies for evaluation. Studies are needed to understand the clinical implications of our findings, diversity during other BSIs, and whether clinical lab practices need revision. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Performance of T2Candida for detecting intra-abdominal candidiasis (IAC) was assessed in 48 high-risk patients. T2Candida sensitivity/specificity and positive/negative predictive values were 33%/93% and 71%/74%, respectively. IAC was present in 100% of cases with concordant positive T2Candida/1,3-beta-d-glucan and absent in 90% of concordant negative results. Combination T2Candida/1,3-beta-d-glucan may help guide treatment decisions. [ABSTRACT FROM AUTHOR]

Background We developed and validated a mouse model of C. albicans IAC that mimics peritonitis and abscesses (IAA) in humans, and that is amenable to temporal–spatial transcriptional profiling and virulence studies. Methods We measured C. albicans SC5314 gene expression by RNA-Seq (RiboPure extraction; Illumina MiSeq) in triplicate during early peritonitis (within 30 minutes of infection), late peritonitis (24 hours) and IAA (48 hours). Differential expression was defined by ≥2-fold differences at false discovery rate ≤0.01. Results ≥7 million C. albicans reads were detected in each experiment. 67% of C. albicans reads mapped to coding sequences, covering 93% of open reading frames. The 50 C. albicans genes most highly expressed during early peritonitis were associated with pH (including RIM101 and PHR1) and oxidative stress responses, and adhesion/hyphal growth (e.g. ALS3, HWP1, ECM331, SAP6). The corresponding 50 C. albicans late peritonitis genes were associated with neutrophil/macrophage responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism, reflecting stress response and nutrient/metal limitation. The top 50 core gene responses for all stages were associated with adhesion, stress response, and glucose transport. Among the most up-regulated genes in late peritonitis and IAA compared with early peritonitis were those involved antifungal drug resistance (CDR family, MDR1, FLU1, and ERG family), although mice were not exposed to antifungals. Null and reconstitution mutants for genes involved in adhesion (ALS3), copper transport (CCC2), DNA (DDI1) and cell wall damage responses (DAP1 homologs), and glycerol biosynthesis (RHR2) were attenuated for virulence in temporal-spatial fashion during peritonitis and IAA, and/or hyper-susceptible to phagocytosis and echinocandins (table). Conclusion C. albicans relies upon diverse biologic processes to cause peritonitis and IAA. Multiple genes induced in response to stress during IAC mediate virulence, phagocyte, and echinocandin resistance. Therefore, pathogenic strategies used by C. albicans during IAC may lessen responses to echinocandin treatment, even in the absence of drug exposure or FKS mutations. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]