- Salmonella and Campylobacter epidemiology
- Antibiotic Resistance in Bacteria
- Vibrio bacteria research studies
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Enterobacteriaceae and Cronobacter Research
- Clostridium difficile and Clostridium perfringens research
- Bacterial Identification and Susceptibility Testing
- Gut microbiota and health
- Antibiotics Pharmacokinetics and Efficacy
- Bacterial biofilms and quorum sensing
- Antimicrobial Resistance in Staphylococcus
- Aquaculture disease management and microbiota
- Hepatitis Viruses Studies and Epidemiology
- Antibiotic Use and Resistance
- Pneumonia and Respiratory Infections
- Animal Virus Infections Studies
- Oral microbiology and periodontitis research
- Plant Pathogenic Bacteria Studies
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Neonatal and Maternal Infections
- Mycobacterium research and diagnosis
- Fecal contamination and water quality
Oxford University Clinical Research Unit
2016-2025
University of Oxford
2013-2024
Hospital for Tropical Diseases
2014-2024
Wellcome/MRC Cambridge Stem Cell Institute
2024
University of Cambridge
2024
Nuffield Orthopaedic Centre
2015-2024
London School of Hygiene & Tropical Medicine
2015-2024
Biotechnology Institute
2024
The University of Melbourne
2024
Stanford University
2024
The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) nearly 2,000 isolates sourced over 60 countries generate a robust genotyping scheme that is phylogenetically informative and compatible with range assays. These show that, exception rapidly disseminating H58 subclade (now...
One of the UN sustainable development goals is to achieve universal access safe and affordable drinking water by 2030. It locations like Kathmandu, Nepal, a densely populated city in South Asia with endemic typhoid fever, where this goal most pertinent. Aiming understand public health implications quality Kathmandu we subjected weekly samples from 10 sources for one year range chemical bacteriological analyses. We additionally aimed detect etiological agents fever longitudinally assess...
Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), remains a serious global health concern. Since their emergence in the mid-1970s multi-drug resistant (MDR) S. now dominate drug sensitive equivalents many regions. MDR is almost exclusively conferred self-transmissible IncHI1 plasmids carrying suite of antimicrobial resistance genes. We identified over 300 single nucleotide polymorphisms (SNPs) within conserved regions plasmid, and genotyped both plasmid chromosomal SNPs...
Significance Shigella sonnei is a globally emerging agent of bacterial dysentery. Here, we use genomics to examine the microevolution S. in Vietnam. We show that was introduced into Vietnam early 1980s, where it continued evolve, spreading geographically establish localized founder populations. The population Ho Chi Minh City has undergone several clonal replacement events, during which small number microevolutionary changes have risen dominance. These changes, induced by horizontal gene...
Typhoid is a systemic infection caused by Salmonella Typhi and Paratyphi A, human-restricted bacteria that are transmitted faeco-orally. S . A clonal, their limited genetic diversity has precluded the identification of long-term transmission networks in areas with high disease burden. To improve our understanding typhoid we have taken novel approach, performing longitudinal spatial case–control study for Nepal, combining single-nucleotide polymorphism genotyping case localization via global...
The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several failures isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. isolates were genome sequenced observations, fever clearance times (FCTs) stratified by lineage. Most belonged to specific H58 subclade. Treatment failure with Typhi-H58 was significantly less frequent...
The use of whole-genome sequencing as a tool for the study infectious bacteria is growing clinical interest. Chlamydia trachomatis responsible sexually transmitted infections and blinding disease trachoma, which affect hundreds millions people worldwide. Recombination widespread within genome C. trachomatis, thus necessary to understand evolution, diversity, epidemiology this pathogen. Culture has, until now, been prerequisite obtain DNA sequencing; however, an obligate intracellular...
There is paucity of data regarding the geographical distribution, incidence, and phylogenetics multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction whole genome sequenced 249 contemporaneous S. isolated between 2008-2015 11 African countries, context 2,057 global genomic framework. Despite broad genetic diversity, majority organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), 2.3.2...
Abstract Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging due to its high levels antimicrobial resistance. Multidrug resistant A. risen rapidly in Vietnam, where colistin becoming the drug last resort for many infections. In this study we generated spontaneous progeny (up >256 μg/μl) from four susceptible Vietnamese isolates one reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used...
Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering and control efforts. Using vitro competition experiments, we assayed fitness of eleven isogenic strains with resistance FQ target genes, gyrA parC. In absence pressure, 6 out 11 mutants carried selective advantage over antimicrobial-sensitive parent strain, indicating...
Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. remains largely unexplored from a genomic standpoint and still described using vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical temporal data to examine natural history species. Our analysis subdivides into seven phylogenetic groups (PGs); each containing two-or-more serotypes characterised by distinct...
Abstract Multidrug‐resistant ( MDR ) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity K. in resource‐poor hospital settings. Through whole‐genome sequencing WGS ), we reconstructed an outbreak occurring on high‐dependency wards Kathmandu during 2012 with case‐fatality rate 75%. The analysis permitted identification two lineages causing distinct outbreaks within complex endemic . Using...
Background Antimicrobial resistance is a major issue in the Shigellae, particularly as specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) becoming globally dominant. Ciprofloxacin recommended treatment for infections. However, ciprofloxacin-resistant S. are being increasingly isolated Asia and sporadically reported on other continents. We hypothesized that primary hub recent international spread sonnei. Methods Findings performed whole-genome sequencing collection 60...
Abstract Background Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity mortality. The rapid increase antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs prescribed antibiotics...
Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with H58 lineage, lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how emerged became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. isolated period spanning emergence. Our dataset, which contains earliest described organism,...
Abstract Background Shigellosis remains considerable public health problem in some developing countries. The nature of Shigellae suggests that they are highly adaptable when placed under selective pressure a human population. This is demonstrated by variation and fluctuations serotypes antimicrobial resistance profile organisms circulating differing setting endemic locations. Antimicrobial the genus Shigella constant threat, with reports Asia being resistant to multiple antimicrobials new...
The objective of this study was to assess the presence mcr-1 in Shigella sonnei isolated Vietnam.WGS data were analysed for gene sequence. association with a plasmid assessed by PCR and conjugation.Through genome sequencing we identified plasmid-associated inactive form 2008 Vietnamese isolate sonnei. conjugated into Escherichia coli activated upon exposure colistin, resulting highly colistin-resistant transconjugants.This is first description Shigella, which atypical given that colistin not...
We recently reported a dramatic increase in the prevalence of carbapenem-resistant Acinetobacter baumannii infections intensive care unit (ICU) Vietnamese hospital. This upsurge was associated with specific oxa23-positive clone that identified by multilocus VNTR analysis. Here, we used whole-genome sequence analysis to dissect emergence A. causing ventilator-associated pneumonia (VAP) ICU during 2009-2012. To provide historical context and distinguish microevolution from strain introduction,...
To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop first human challenge model Salmonella enterica serovar Paratyphi A infection.Two groups 20 participants underwent oral with S. following sodium bicarbonate pretreatment at 1 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.5-1 CFU). Participants were monitored in an outpatient setting daily clinical review collection blood stool cultures. Antibiotic treatment was started when...
Salmonella Typhimurium is a major diarrheal pathogen and associated with invasive nontyphoid (iNTS) disease in vulnerable populations. We present the first characterization of iNTS organisms Southeast Asia describe different evolutionary trajectory from that causing sub-Saharan Africa. In Vietnam, globally distributed monophasic variant Typhimurium, serovar I:4,[5],12:i:− ST34 clone, has reacquired phase 2 flagellum gained multidrug-resistant plasmid to become HIV-infected patients. document...
We performed a prospective multicenter study to address the lack of data on etiology, clinical and demographic features hospitalized pediatric diarrhea in Ho Chi Minh City (HCMC), Vietnam. Over 2,000 (1,419 symptomatic 609 non-diarrheal control) children were enrolled three hospitals over 1-year period 2009–2010. Aiming detect panel pathogens, we identified known diarrheal pathogen stool samples from 1,067/1,419 (75.2%) with 81/609 (13.3%) without diarrhea. Rotavirus predominated (664/1,419;...