To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.

Foodborne-associated bacteria with increased incidence of antimicrobial drug resistance were the most common cause.

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Fouling caused by organic matter and bacteria remains a significant challenge for the membrane-based desalination industry. Fouling decreases the permeate quality and membrane performance and also increases energy demands. Here, we quantified the amount of organic matter and bacteria at several stages along the water-treatment train of an integrated ultrafiltration–nanofiltration seawater treatment pilot plant. We quantified the organic matter, in terms of Total Organic Carbon (TOC) and Assimilable Organic Carbon (AOC), and evaluated its composition using Liquid Chromatography for Organic Carbon Detection (LC-OCD). The bacterial cells were counted using Bactiquant. We found that ultrafiltration (UF) was effective at removing bacterial cells (99.7%) but not TOC. By contrast, nanofiltration (NF) successfully removed both TOC (95%) and bacterial cells. However, the NF permeate showed higher amounts of AOC than seawater. LC-OCD analysis suggested that the AOC was mostly composed of low molecular weight neutral substances. Furthermore, we found that the cleaning of the UF membrane using chemically enhanced backwash reduced the amount of AOC released into the UF permeate. By implementing the cleaning-in-place of the NF membrane, the pressure drop was restored to the normal level. Our results show that the UF and NF membrane cleaning regimes investigated in this study improved membrane performance. However, AOC remained the hardest-to-treat fraction of organic carbon. AOC should, therefore, be monitored closely and regularly to mitigate biofouling in downstream processes.

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