Browsing by Author "McKenzie J"

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    Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment.
    (Nature Portfolio, 2023-08-23) Sulit AK; Daigneault M; Allen-Vercoe E; Silander OK; Hock B; McKenzie J; Pearson J; Frizelle FA; Schmeier S; Purcell R
    Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.
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    Development of a cross-sectoral antimicrobial resistance capability assessment framework.
    (BMJ Publishing Group, 2024-02-05) Ferdinand AS; McEwan C; Lin C; Betham K; Kandan K; Tamolsaian G; Pugeva B; McKenzie J; Browning G; Gilkerson J; Coppo M; James R; Peel T; Levy S; Townell N; Jenney A; Stewardson A; Cameron D; Macintyre A; Buising K; Howden BP; Biswas S
    Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR.
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    Prevalence of Antimicrobial Resistance in Escherichia coli and Salmonella Species Isolates from Chickens in Live Bird Markets and Boot Swabs from Layer Farms in Timor-Leste.
    (MDPI (Basel, Switzerland), 2024-01-25) Pereira A; Sidjabat HE; Davis S; Vong da Silva PG; Alves A; Dos Santos C; Jong JBDC; da Conceição F; Felipe NDJ; Ximenes A; Nunes J; Fária IDR; Lopes I; Barnes TS; McKenzie J; Oakley T; Francis JR; Yan J; Ting S; Ahn J
    The rapid emergence of antimicrobial resistance is a global concern, and high levels of resistance have been detected in chicken populations worldwide. The purpose of this study was to determine the prevalence of antimicrobial resistance in Escherichia coli and Salmonella spp. isolated from healthy chickens in Timor-Leste. Through a cross-sectional study, cloacal swabs and boot swabs were collected from 25 live bird markets and two layer farms respectively. E. coli and Salmonella spp. from these samples were tested for susceptibility to six antimicrobials using a disk diffusion test, and a subset was tested for susceptibility to 27 antimicrobials using broth-based microdilution. E. coli and Salmonella spp. isolates showed the highest resistance towards either tetracycline or ampicillin on the disk diffusion test. E. coli from layer farms (odds ratio:5.2; 95%CI 2.0-13.1) and broilers (odds ratio:18.1; 95%CI 5.3-61.2) were more likely to be multi-drug resistant than those from local chickens. Based on the broth-based microdilution test, resistance to antimicrobials in the Timor-Leste Antimicrobial Guidelines for humans were low, except for resistance to ciprofloxacin in Salmonella spp. (47.1%). Colistin resistance in E. coli was 6.6%. Although this study shows that antimicrobial resistance in chickens was generally low in Timor-Leste, there should be ongoing monitoring in commercial chickens as industry growth might be accompanied with increased antimicrobial use.