By 2030, the global population will be 8.5 billion, placing pressure on international poultry production, of which China is a key producer. From April 2017, China will implement the withdrawal of colistin as a growth promoter, removing over 8,000 tonnes per year from the Chinese farming sector. To understand the impact of banning colistin and the epidemiology of multi-drug-resistant (MDR) Escherichia coli (using bla and mcr-1 as marker genes), we sampled poultry, dogs, sewage, wild birds and flies. Here, we show that mcr-1, but not bla, is prevalent in hatcheries, but bla quickly contaminates flocks through dogs, flies and wild birds. We also screened samples directly for resistance genes to understand the true breadth and depth of the environmental and animal resistome. Direct sample testing for bla and mcr-1 in hatcheries, commercial farms, a slaughterhouse and supermarkets revealed considerably higher levels of positive samples than the bla- and mcr-1-positive E. coli, indicating a substantial segment of unseen resistome-a phenomenon we have termed the 'phantom resistome'. Whole-genome sequencing identified common bla-positive E. coli shared among farms, flies, dogs and farmers, providing direct evidence of carbapenem-resistant E. coli transmission and environmental contamination.

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BaCKgRoUND aND aIMS: Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase silent information regulator 1 (SIRT1) was discovered in HCC, and its presence is positively correlated with malignancy and metastasis. N 6-methyladenosine (m 6 A) is the most prominent modification, but the exact mechanisms on how SIRT1 regulates m 6 A modification to induce hepatocarcinogenesis remain unclear. appRoaCH aND ReSUltS: Here we demonstrate that SIRT1 exerts an oncogenic role by down-regulating fat mass and obesity-associated protein (FTO), which is an m 6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1, and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is identified as m 6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m 6 A + GNAO1 and down-regulates its mRNA expression. CoNClUSIoNS: We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m 6 A + of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a target of SIRT1 for therapeutic agents to treat HCC.

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