Piperacillin/tazobactam resistance in a clinical isolate of Escherichia coli due to IS26-mediated amplification of blaTEM-1B

© 2020 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41467-020-18668-2A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the β-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here, we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked pseudo-compound transposon, PTn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.This work was supported by the Liverpool School of Tropical Medicine Director’s Catalyst Fund awarded to A.T.M.H. and T.E. A.P.R. would like to acknowledge funding from the AMR Cross-Council Initiative through a grant from the Medical Research Council, a Council of UK Research and Innovation (Grant number; MR/S004793/1), and funding from the National Institute for Health Research. (Grant Number; NIHR200632).Published versio

Exploring subjective constructions of health in China: a Q-methodological investigation

Background: With an increasing awareness of people’s satisfaction and feeling, health-related quality of life (HRQoL) has become an essential aspect of measuring health. HRQoL is fundamentally a foreign concept introduced to China from the West. While a growing number of studies applied western HRQoL measures, few content validity tests examined the legitimacy of applying Western developed HRQoL measures in a Chinese cultural setting. If there are distinct differences in health conceptualisation between China and the West, it can be argued that those western measures may fail to ask the most appropriate and important questions among a Chinese population in assessing health. As a limited number of studies have investigated Chinese people’s understandings of health, this study aimed to explore how health is defined and described in China. Methods: A Q-methodological study was conducted to explore subjective constructions of health among Chinese participants. A scoping review of Chinese generic HRQoL measures, supplemented by a series of qualitative interviews conducted in China, produced a list of 42 statements representing aspects of health considered as being important in a Chinese cultural setting. Chinese participants in face-to-face interviews ranked and sorted these statements. Data were analysed to identify clusters of participants who shared a similar perspective, using a by-person factor analysis procedure. Results: 110 Chinese participants with various demographics characteristics completed sorting interviews. Five independent factors emerged: (I) “Physical independence and social interaction skills”; (II) “Physical health”; (III) “Sensations and feelings”; (IV) “Lifestyles”; (V) “Learning and working abilities”. Conclusions: The Q-study showed that many health statements were rated highly as most important by a diverse range of Chinese participants but were not covered in the commonly used Western HRQoL measure EQ-5D. It then suggests that the EQ-5D descriptive system might need modification to improve its capacity to measure health status in China. The study thus raises a general question as to how appropriate the Western-developed HRQoL measures are when used to assess health in a significantly different cultural setting

Genome-wide characterization of genetic variants and putative regions under selection in meat and egg-type chicken lines

Abstract\ud \ud Background\ud Meat and egg-type chickens have been selected for several generations for different traits. Artificial and natural selection for different phenotypes can change frequency of genetic variants, leaving particular genomic footprints throghtout the genome. Thus, the aims of this study were to sequence 28 chickens from two Brazilian lines (meat and white egg-type) and use this information to characterize genome-wide genetic variations, identify putative regions under selection using Fst method, and find putative pathways under selection.\ud \ud \ud Results\ud A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more variants detected from the broiler (meat-type) line. Although most were located in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512 stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter protein functions. Genes harboring intolerant non-synonymous SNPs affected metabolic pathways related mainly to reproduction and endocrine systems in the white-egg layer line, and lipid metabolism and metabolic diseases in the broiler line. Fst analysis in sliding windows, using SNPs and INDELs separately, identified over 300 putative regions of selection overlapping with more than 250 genes. For the first time in chicken, INDEL variants were considered for selection signature analysis, showing high level of correlation in results between SNP and INDEL data. The putative regions of selection signatures revealed interesting candidate genes and pathways related to important phenotypic traits in chicken, such as lipid metabolism, growth, reproduction, and cardiac development.\ud \ud \ud Conclusions\ud In this study, Fst method was applied to identify high confidence putative regions under selection, providing novel insights into selection footprints that can help elucidate the functional mechanisms underlying different phenotypic traits relevant to meat and egg-type chicken lines. In addition, we generated a large catalog of line-specific and common genetic variants from a Brazilian broiler and a white egg layer line that can be used for genomic studies involving association analysis with phenotypes of economic interest to the poultry industry.CB received a fellowship from the program Science Without Borders - National Council for Scientific and Technological Development (CNPq, grant 370620/2013–5). GCMM and TFG received fellowships from São Paulo Research Foundation (FAPESP, grants 14/21380–9 and 15/00616–7). LLC is recipient of productivity fellowship from CNPq. This project was funded by São Paulo Research Foundation (FAPESP) - thematic project (2014/08704–0)