Timothy R Walsh

Timothy R Walsh
Cardiff University | CU · Cardiff Institute of Infection & Immunity

About

385
Publications
84,840
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35,564
Citations
Citations since 2016
158 Research Items
21607 Citations
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201620172018201920202021202201,0002,0003,000
201620172018201920202021202201,0002,0003,000

Publications

Publications (385)
Article
Full-text available
Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a 'last line of defence' antibiotic. Using experimental evolution, we show that a plasmid carrying the...
Article
Full-text available
Background In low- and middle-income countries (LMIC) Staphylococcus aureus is regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB). Methods We characterised GPB isolates from neonatal blood cultures from L...
Article
This study was designed to investigate the molecular epidemiology of mobile colistin resistance (mcr) using a “One-Health” approach in Laos and to predict whether any dominant plasmid backbone and/or strain type influences the dissemination of mcr. We collected 673 samples from humans (rectal normal flora), poultry, and the environment (water, flie...
Article
Full-text available
Background Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 to September 2017. Methods We enrolled patients and collected epidemiology and outcome data. All Entero...
Article
Although carbapenem use is prohibited in animals in China, carbapenem-resistant Escherichia coli (CREC), especially New Delhi metallo-β-lactamase (NDM)-producing strains, are widely prevalent in food-producing animals. At present, the impact of livestock-associated CREC strains on human populations at the national level is unknown. Here, we conduct...
Article
Full-text available
Long-read sequencing (LRS) can resolve repetitive regions, a limitation of short read (SR) data. Reduced cost and instrument size has led to a steady increase in LRS across diagnostics and research. Here, we re-basecalled FAST5 data sequenced between 2018 and 2021 and analyzed the data in relation to gDNA across a large dataset ( n = 200) spanning...
Article
Full-text available
Kirsty Sands,1,2 Owen B Spiller,2 Kathryn Thomson,1,2 Edward AR Portal,2 Kenneth C Iregbu,3 Timothy R Walsh1,2 1Ineos Institute of Antimicrobial Research, Department of Zoology, University of Oxford, Oxford, UK; 2Division of Infection and Immunity, Cardiff University, Cardiff, UK; 3National Hospital Abuja, Abuja, NigeriaCorrespondence: Kirsty Sands...
Article
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Antimicrobial use in livestock production is linked to the emergence and spread of antimicrobial resistance (AMR), but large-scale studies on AMR changes in livestock isolates remain scarce. Here we applied whole-genome sequence analysis to 982 animal-derived Escherichia coli samples collected in China from the 1970s to 2019, finding that the numbe...
Preprint
Full-text available
Bacterial pathogens show high levels of standing genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance remains unclear. Here we address this problem in the context of colistin, a last line of defense antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gen...
Article
Full-text available
Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent str...
Article
Full-text available
Objectives To provide a comprehensive assessment of the impact of carbapenem resistance on mortality among patients infected with Enterobacteriaceae and to explore the source of heterogeneity across studies. Design This systematic review was conducted following the guidelines of Cochrane Guidance and the Preferred Reporting Items for Systematic Re...
Article
Full-text available
Understanding how multidrug-resistant Enterobacterales (MDRE) are transmitted in low- and middle-income countries (LMICs) is critical for implementing robust policies to curb the increasing burden of antimicrobial resistance (AMR). Here, we analysed samples from surgical site infections (SSIs), hospital surfaces (HSs) and arthropods (summer and win...
Article
Full-text available
Mobile colistin resistance enzyme MCR‐3 is a phosphoethanolamine transferase modifying lipid A in Gram‐negative bacteria. MCR‐3 generally mediates low‐level (≤8 mg L−1) colistin resistance among Enterobacteriaceae, but occasionally confers high‐level (>128 mg L−1) resistance in aeromonads. Herein, it is determined that MCR‐3, together with another...
Article
Full-text available
Introduction Newborn sepsis accounts for more than a third of neonatal deaths globally and one in five neonatal deaths in Ethiopia. The first-line treatment recommended by WHO is the combination of gentamicin with ampicillin or benzylpenicillin. Gram-negative bacteria (GNB) are increasingly resistant to previously effective antibiotics. Objectives...
Article
Full-text available
Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens...
Article
Polymyxin resistance is a public health concern, present in humans, animals and the environment, occasioned by chromosomal- or plasmid-encoding mechanisms. Chromosomal alterations in MgrB are frequently detected in Klebsiella spp., but not yet reported and characterised in K. variicola. Here, we performed microbiological and genomic characterisatio...
Article
The recent emergence of mobile-tigecycline resistance tet(X) genes in human and animals in China seriously threats the clinical utility of tigecycline. Here we focused on the isolation and molecular characterization of plasmid-mediated tigecycline resistance tet(X4)-positive E. coli from different sources in Pakistan using MinION and Illumina seque...
Preprint
Full-text available
Antimicrobial agents have been used in meat production for decades and its consumption is considered an key driver for the emergence and dissemination of antimicrobial resistance (AMR). However, large-scale studies on AMR changes in animal isolates since the introduction of antimicrobial usage remain scarce. We applied whole genome sequencing analy...
Article
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Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was init...
Article
Aim: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) particularly New Delhi metallo-β-lactamase (NDM) is a serious public health concern globally. The aim of the study to determine the molecular epidemiology of bla NDM -producing clinically isolated K. pneumoniae. Methods: Carbapenem-resistant K. pneumoniae isolates (n = 100) were collected from...
Article
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Novel therapeutics designed to target the polymeric matrix of biofilms requires innovative techniques to accurately assess their efficacy. Here, multiple particle tracking (MPT) was developed to characterize the physical and mechanical properties of antimicrobial resistant (AMR) bacterial biofilms and to quantify the effects of antibiotic treatment...
Article
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Mobile colistin resistance gene mcr-1 and extended-spectrum β-lactamase gene bla CTX-M are highly prevalent in human- and pet-derived bacteria. Isolation of identical strains of mcr-1-positive Escherichia coli (MCRPEC) or bla CTX-M-positive E. coli (CTX-MPEC) from pets and humans highlighted the potential for co-colonization of antibiotic-resistant...
Article
We performed the characterization of a multidrug-resistant (MDR) Enterobacter spp. isolate highlighting the genetic aspects of the antimicrobial resistance genes. An Enterobacter spp. isolate (Ec61) was recovered in 2014 from a transtracheal aspirate sample from a patient admitted to a Brazilian tertiary hospital and submitted to further microbiolo...
Article
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Objectives Many clinical laboratories have difficulty in routinely performing in vitro fosfomycin susceptibility testing using the agar dilution (AD) method, considered to be the gold standard method. The objective of our work was to evaluate a rapid commercial fosfomycin agar dilution panel against clinical Staphylococcus aureus and Enterobacteral...
Article
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Objectives Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset in the current therapeutic arsenal to treat these infections. We examined aminoglycoside resistance phenotypes and genomics in a collection of 100 invasive KPC-producing K. pneumoniae isolates sequentially collected in...
Article
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The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens1,2,3. Although aspects of IncC plasmid conjugation have been well studied4,5,6,7,8,9, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated transposon mutagenesis an...
Article
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This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolat...
Article
The global dissemination of antibiotic resistance genes (ARGs) and their role as novel contaminants has garnered significant attention. However, the prevalence of ARGs in farm environments is usually underestimated and understudied. Here, colistin resistance gene mcr-1 and extended-spectrum β-lactamase (ESBL) and carbapenemase genes, all of which p...
Conference Paper
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Despite the high prevalence of antimicrobial resistance (AMR) in developing countries, limited data is available informing the actual health burden. We undertook a prospective cohort study at Dhaka Medical College Hospital (DMCH) to investigate the impact of AMR on health.
Conference Paper
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Emergence of colistin resistance in Klebsiella pneumoniae has become a serious concern in clinical practice, compromising treatment options for life-threatening infections. Here we gnomically describe the emergence of a K. pneumoniae isolate harbouring mcr-8.
Article
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Escherichia coli sequence type 131 (ST131) is well known for its multidrug resistance profile. Carbapenems have been considered the treatment of choice for E. coli ST131 infections, and resistance to carbapenems is emerging due to the acquisition of carbapenemase-encoding genes. In this study, 45 carbapenem-resistant E. coli strains were collected...
Article
Objectives: This study was designed to understand the prevalence of antibiotic-resistant bacteria in the Beijing subway environment and the potential transmission of carbapenem-resistant Enterobacteriaceae in a public transportation environment. Methods: Carbapenem-resistant isolates were selected on brain heart infusion agar supplemented with m...
Article
In the present study, we identified a plasmid-borne optrA gene that meditates resistance to linezolid and phenicols in C. perfringens...
Article
The identification of the first mobile colistin resistance (MCR) gene, mcr-1, in 2015 triggered a rash of mcr screening reports. Subsequently, nine MCR-family genes and their variants have been described. However, a comprehensive overview concerning the epidemiology of the whole MCR family, which is essential for facilitating rational interventions...
Preprint
Full-text available
Escherichia coli Sequence Type (ST)101 is an emerging, multi-drug resistant lineage associated with carbapenem resistance. We recently completed a comprehensive genomics study on mobile genetic elements (MGEs) and their role in bla NDM-1 dissemination within the ST101 lineage. DNA methyltransferases (MTases) are also frequently associated with MGEs...
Article
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While carbapenem use is prohibited in the poultry production chain and carbapenem-resistant Enterobacteriaceae (CRE) are absent from hatchery farms, New Delhi metallo-β-lactamase-producing CRE contamination of commercial broiler chicken farms (grow-out farms) can occur via living hosts such as flies. However, it is not known whether the inanimate f...
Article
Background: Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evalua...
Article
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Background Burkholderia cepacia complex (Bcc) is a group of serious pathogens in cystic fibrosis patients and causes life threatening infections in immunocompromised patients. Species within the Bcc are widely distributed within the environment, can survive the presence of disinfectants and antiseptics, and are inherently multidrug resistant (MDR)....
Article
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There is a marked paucity in our understanding of the epidemiology of colistin-resistant bacterial pathogens in South Asia. A report by Davies and Walsh (Lancet Infect Dis 18:256–257, https://doi.org/10.1016/S1473-3099(18)30072-0 , 2018) suggests the export of colistin from China to India, Vietnam, and South Korea in 2016 was approximately 1,000 to...
Article
Full-text available
The wide dissemination of New Delhi metallo-β-lactamase genes (blaNDM) has resulted in the treatment failure of most available β-lactam antibiotics, with IncX3-type blaNDM-5-carrying plasmids recognised as having spread worldwide. In China, bacteria carrying these plasmids are increasingly being detected from diverse samples, including hospitals, c...
Article
Colistin resistance has attracted substantial attention after colistin was considered as a last‐resort drug for the treatment of infections caused by carbapenem‐resistant and/or multidrug‐resistant (MDR) Gram‐negative bacteria in clinical settings. However, with the discovery of highly mobile colistin resistance (mcr) genes, colistin resistance has...
Article
Objectives: To report a novel tigecycline resistance gene, tet(X6), and its variants in four bacterial species isolated from chickens and pigs in China. Methods: WGS was conducted to identify the suspected resistance genes in the tigecycline-resistant Myroides phaeus 18QD1AZ29W. Functional cloning, homology modelling and molecular docking were p...
Article
This study describes the characterization of four KPC-2-producing Klebsiella pneumoniae strains from neonates belonging to a single sequence type 147 (ST147) in relation to carbapenem resistance and explores probable mechanisms of differential colistin resistance among the clonal cluster. Whole Genome Sequencing revealed that the isolates were near...
Article
Full-text available
The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost...
Preprint
Full-text available
Carbapenems are last-resort antibiotics; however, the spread of plasmid-encoded carbapenemases such as the New Delhi metallo-β-lactamase 1 (NDM-1) challenges their effectiveness. The rise of NDM-1 has coincided with the emergence of extensively multidrug resistant (MDR) lineages such as Escherichia coli ST101. Here we present a comprehensive genomi...
Article
Full-text available
Background: Carbapenemase-producing K. pneumoniae have become a global priority, not least in low-middle income countries. Here, we report the emergence and clinical impact of a novel KPC-K. pneumoniae ST16 clone in a Clonal Complex (CC)258 endemic setting. Methods: In a teaching Brazilian hospital, a retrospective cohort of adult KPC-KP bloodst...
Article
A novel, plasmid-mediated, high-level tigecycline resistance tet (X) gene variant, tet (X5), was detected in a clinical Acinetobacter baumannii isolate from China in 2017. Tet(X5) shows 84.5% and 90.5% amino acid identity to Tet(X3) and Tet(X4), respectively, with similar binding sites and a comparable affinity for tetracyclines. The tet (X5)-conta...
Article
Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in both humans and animals poses a global threat to public health. However, the transmission of CRE between humans and animals has not yet been well studied. Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission b...