Timothy Walsh - Selected Publications#

H-index 94. i10-index 251. Total citations 46,238 (as of 27.12.22)

1) Qiu E. Yang, Xiaodan Ma, Lingshuang Zeng, Qinqin Wang, Lin Teng, Mingzhen He, Chen Liu, Mengshi Zhao, Mengzhu Wang, Jonas Stenløkke Madsen, Hanpeng Liao, Shungui Zhou and Timothy R. Walsh. Interphylum dissemination of carbapenem resistance under environmental conditions: the tip of the iceberg in One-Health AMR. Lancet Microbe. 2023. (in press).

2) Umair M, Hasan B, Farzana R, Ali Q, Sands K, Mathias J, Afegbua S, Haque N, Mashkoor M, Walsh, TR. International manufacturing and trade in colistin, its implications in polymyxin resistance and One-Health global policies: a microbiological, economic and anthropological study. Lancet Microbe. 2023. (IF 86.2 – in press). [Senior author, designed the study and responsible for the funding. Umair (first author)is my PhD student]. Recently accepted in Lancet Microbe, this article will be the first global report looking at the import and export of colistin in farming including its implications on the development of colistin resistance in LMICs.

3) Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. (IF 202.7). 2022 Feb 12;399(10325):629-655. doi: 10.1016/S0140-6736(21)02724-0. (Cited 1624 times). Epub 2022 Jan 19. Our group contributed the largest and most complete neonatal AMR burden dataset – hence why I was listed as an author. This article is possibly the most seminal article on AMR to be published in the last decade and why in less than a year it has already generated over 1600 citations.

4) Brem J, Panduwawala T, Hansen JU, Hewitt J, Liepins E, Donets P, Espina L, Farley A, Shubin K, Campillos GG, Kiuru P, Shishodia S, Krahn D, Lesniak R, Schmidt S, Calvopina K, Turrientes MC, Kavanagh ME, Lubriks D, Hinchliffe P, Langley G, Aboklaish AF, Eneroth A, Backlund M, Baran AG, Nielsen E, Speake M, Kuka J, Robinson J, Grinberga S, Robinson L, McDonough M, Rydzik A, Leissing T, Jimenez-Castellanos JC, Avison MB, Da Silva Pinto S, Pannifer AD, Martjuga M, Widlake E, Priede M, Navratilova IH, Gniadkowski M, Belfrage AK, Yli-Kauhaluoma J, Bacque E, Page MGP, Björkling F, Tyrrell JM, Spencer J, Baranczewski P, Canton R, McElroy SP, Jones PS, Baquero F, Suna E, Morrison A, Walsh TR and Schofield CJ. Imitation of β-Lactam binding enables broad spectrum metallo-β-Lactamase inhibitors. Nat Chem (IF 24.3). 14, 15–24 (2022). https://doi.org/10.1038/s41557-021-00831-x. Cited 16 times. [Co-senior author and responsible for the microbiology and the funding – IMI ENABLE program where I am also a member of the program management committee].

5) Hassan B, Ijaz M, Khan A, Sands K, Serfa G-I, Clayfiel L, El-Bouseary MM, Lai G, Porter E, Khan A, Watkins WJ, Parkhill J, Walsh TR. A role for arthropods as vectors of multi-drug resistant Enterobacterales in surgical site infections from South Asia. Nat Microbiol (IF 30.1) 2021. Oct;6 (10):1259-1270. doi: 10.1038/s41564-021-00965-1. Cited 6 times. [Senior author, designed the study and responsible for the funding. Brekhna Hassan was my PhD student and submitted this work as part of her PhD thesis]. Although a very recent article and therefore not yet cited, this study, using SNP analysis, is the first to definitively show a link/connection between patients, hospital surfaces and arthropods (mainly insects). The study was undertaken over two seasons where the vectors for MDR bacteria transmission were entirely different – flies for the summer and cockroaches for the winter. The levels of resistant bacteria carried by the arthropods were extremely high. Notably, this study links the transmission of AMR to climate change. Our modelling, linked to climate change mapping, predicts that 5000 trillion flies will be carrying carbapenem-resistant bacteria. The also study attracted significant press attention including discussions with the WHO, FAO and OIE. The Wellcome Trust has invited us to submit a grant including examining interventions. Nature Microbiology chose our story and image for the front cover.

6) Thomson KM, Dyer C, Liu F, Sands K, Portal E, Carvalho MJ, Barrell M, Boostrom I, Dunachie S, Farzana R, Ferreira A, Frayne F, Hassan B, Jones E, Jones L, Mathias J, Milton R, Rees J, Chan GJ, Bekele D, Mahlet A, Basu S, Nandy RK, Saha B, Iregbu K, Modibbo F, Uwaezuoke S, Zahra R, Shirazi H, Syed NU, Mazarati JB, Rucogoza A, Gaju L, Mehtar S, Bulabula ANH, Whitelaw A, BARNARDS Group, van Hasselt JGC and Walsh TR. Evaluating the roles of antibiotic resistance, drug target attainment, bacterial pathogenicity, virulence and antibiotic access and affordability in affecting outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective study. Lancet Infect Dis. (IF 74.1). 2020 Aug 9:S1473-3099(21)00050-5. doi: 10.1016/S1473-3099(21)00050-5. Cited 29 times. [Senior author, designed the study and responsible for the funding (Gates Foundation). Katy Thomson is my PhD student and had submitted this work as part of her PhD].

In terms of message, this is the most important article I have ever written. The article was part of the BARNARDS publication strategy and follows on from article #4 (we also have two additional articles under review [not listed] – one in Nature Microbiology and the other in Lancet Global Health). Since 2011, the WHO have recommended ampicillin and gentamicin for the treatment of neonatal sepsis; however, this publication raises serious doubt over this advice, and we show that alternative therapies such as ceftazidime and amikacin result in a marked increased survival rate. We have subsequently had discussions with the WHO and are now collaborating with St. Georges (Sharland) and GARDP to initiate intervention trials in South Asia and Africa. This article, also for the first time, examined the access and cost of antibiotics, deferral payments to patients, average salaries, and health insurance – again, this has initiated several discussions with the WHO.

7) Sands K, Carvalho MJ, Portal E, Thomson K, Dyer C, Akpulu C, Andrews R, Ferreira A, Gillespie D, Hender T, Hood K, Mathias J, Milton R, Nieto M, Taiyari, K, Chan GJ, Bekele D, Solomon S, Basu S,Chattopadhyay P, Mukherjee S, Iregbu K, Modibbo F, Uwaezuoke S, Zahra R, Shirazi H, Muhammad A, Mazarati JB, Rucogoza A, Gaju L, Mehtar S, Bulabula ANH, Whitelaw A; BARNARDS Group, Walsh TR. Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Nat Microbiol. (IF 30.1). 2021 Apr;6(4):512-523. doi: 10.1038/s41564-021-00870-7. Cited 85 times. [Senior author. Designed the study and responsible for the funding (Gates Foundation). Kirsty Sands is a postdoc in my lab and, as were many others, funded by the Gates Foundation].

8) Wang Y, Xu C, Zhang R, Chen Y, Shen Y, Hu F, Liu D, .\Lu J, Guo Y, Xia X, Jiang J, Wang X, Fu Y, Yang L, Wang J, Li J, Cai C, Yin D, Che J, Fan R, Wang Y, Qing Y, Li Y, Liao K, Chen H, Zou M, Liang L, Tang J, Shen Z, Wang S, Yang X, Wu C, Xu S, Walsh TR, Shen J. Changes in colistin resistance and mcr-1 abundance in Escherichia coli of animal and human origins following the ban of colistin-positive additives in China: an epidemiological comparative study. Lancet Infect Dis. (IF 74.1). 2020 Oct;20(10):1161-1171. doi: 10.1016/S1473-3099(20)30149-3. Cited 115 times. [Co-senior author. Together with Prof Wang, this article is part of the DXC-HUB award by the MRC/NSFC of which I am the UK lead and Yang Wang the Beijing lead. The study was designed by me in a meeting I conveyed in Berkeley, Sep 2019. I also wrote the article with Yang Wang].

9) He T, Wang R, Liu D, Walsh TR, Zhang R, Lv Y, Ke Y, Ji Q, Wei R, Liu Z, Shen Y, Wang G, Sun L, Lei L, Lv Z, Li Y, Pang M, Wang L, Sun Q, Fu Y, Song H, Hao Y, Shen Z, Wang S, Chen G, Wu C, Shen J, Wang Y. Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans. Nat Microbiol. (IF 30.1). 2019 Sep;4(9):1450-1456. doi: 10.1038/s41564-019-0445-2. Cited 287 times. [This work was created from the DXC-HUB grant and its predecessor (Deter-XDR-China) also funded by MRC (Newton Fund) and NSFC, and as part of our on-going collaborations and surveillance in China. For this article, I jointly designed the figures, did the modelling and edited the paper throughout many iterations].

In the last two years, this article has been published over 200 times and its citation rate continues to rise and will exceed 1000 citations. This was the first article to describe plasmid mediated resistance to tigecycline – a last resort antibiotic to treat very serious Gram-negtive infections. Furthermore, we have shown that this mechanism of resistance, TetX, is driven by the use of oxytetracycline in animals. These data and this article further encouraged the Chinese government to ban all antibiotics as growth promoters which came into effect in 2020 (http://www.xmsyj.moa.gov.cn/zcjd/201907/t20190710_6320678.htm, https://www.phiphar.com/the-announcement-no-194-of-the-ministry-of-agriculture-and-rural-affairs-of-the-peoples-republic-of-china). Given the about we are analysing all genomic data with the intention of writing a comprehensive review on Tex genes. Furthermore, we have submitted an EOI to the Wellcome Trust Discovery Award seeking to fund a program on TetX inhibitors.

10) Wang Y, Zhang R, Li J, Wu Z, Yin W, Schwarz S, Tyrrell JM, Zheng Y, Wang S, Shen Z, Liu Z, Liu J, Lei L, Li M, Zhang Q, Wu C, Zhang Q, Wu Y, Walsh TR, Shen J. Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production. Nat Microbiol. (IF 30.1). 2017 Feb 6;2:16260. doi: 10.1038/nmicrobiol.2016.260. Cited 333 times. [Co-senior author. This article was written by Yang Wang and I. Jianzhong Shen was the PI of the NSFC grant so he became senior author. The idea of this study was started in 2014 when Yang and I met in Chicago at an ASM meeting. Together we designed the experiments, particularly the environmental sampling. We designed the figures and also that of the front cover of Nature Microbiology].

11) Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. (IF 74.1) 2016 Feb;16(2):161-8. doi: 10.1016/S1473-3099(15)00424-7. Cited 4671 times. [Joint lead author. This article was the first global report of mobile colistin resistance as outline in my description to article #28. In splitting the original 4,200-word article (I wanted to write the most complete report on a new resistance mechanism), the Lancet ID unusually published a non-clinical paper. As well as doing the global colistin sales analysis I mainly wrote the whole article and designed the figures as well as oversaw the in-vivo work. The funder was MRC (I am PI) and NSFC].

As judged by the fact that this article has been cited nearly 4000 times in 5 years speaks of its scientific significance. This was the first article to announce the arrival of mobile resistance to colistin – an antibiotic reserved for serious Gram-negative infections only. The follow up study was #28 and Prof. Gonging Wu and I wrote an article (#31) announcing that China will ban colistin from animal feed which they did within 7 months following meetings with me, Prof. Wu, Prof. Jianzhong Shen and the Chinese Ministries for Agriculture (CMA) and Health (CMH). The world press reaction was predictably high with countless interviews in the UK and China: https://www.newton-gcrf.org/impact/stories-of-change/slowing-the-spread-of-antibiotic-resistance), (https://www.nature.com/articles/d41586-020-02889-y, Furthermore, policy changed was now being driven across world authorities - https://agris.fao.org/agris-search/search.do?recordID=US201900436520, and https://www.cdc.gov/drugresistance/solutions-initiative/stories/gene-reported-mcr.html. We continue to work with the Chinese authorities to ban all production on animal-feed colistin including that for export.