Brian Spratt

Brian Spratt
Imperial College London | Imperial · Infectious Disease Epidemiology, School Public Health, Faculty of Medicine

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450
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Publications

Publications (450)
Article
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Antibiotic resistance forms a serious threat to the health of hospitalised patients, rendering otherwise treatable bacterial infections potentially life-threatening. A thorough understanding of the mechanisms by which resistance spreads between patients in different hospitals is required in order to design effective control strategies. We measured...
Article
The environmental bacterium Burkholderia pseudomallei causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 B. pseudomallei isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data point to Australia as a...
Article
The environmental bacterium $\textit{Burkholderia pseudomallei}$ causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 $\textit{B. pseudomallei}$isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data po...
Article
Full-text available
Visualization is frequently used to aid our interpretation of complex datasets. Within microbial genomics, visualizing the relationships between multiple genomes as a tree provides a framework onto which associated data (geographical, temporal, phenotypic and epidemiological) are added to generate hypotheses and to explore the dynamics of the syste...
Article
Full-text available
The Burkholderia pseudomallei multilocus sequence typing (MLST) database (http://pubmlst.org/bpseudomallei/) contains the largest global sequence repository for B. pseudomallei and its closest genetic relatives. Using conventional MLST and in silico MLST data derived from publicly available whole-genome sequences, we first defined the phylogenetic...
Article
Full-text available
Unlabelled: The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial vi...
Article
Full-text available
Unlabelled: Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale b...
Data
List of 132 genomes in the Sheffield data set.
Data
(A) Maximum likelihood tree reconstructed for the Sheffield genomes. (B) Temporal signal in the tree. The signal was strong enough to estimate the evolutionary rate shown by the solid line. Download
Data
Distribution of TMRCA between pairs of genomes in the Sheffield data set that have been assessed to be directly linked by Outbreaker (red) or not (blue). Download
Data
Links between the London genomes, based on the 8-month maximum TMRCA criterion. Download
Data
List of 105 genomes in the London data set.
Data
Permutation test comparing the mean TMRCA for known sexual contacts (in red) with values that would be obtained if the sexual contact labels were permuted at random (histogram). Download
Data
Links between the Sheffield genomes, based on the 8-month maximum TMRCA criterion. Download
Data
(A) Maximum likelihood tree reconstructed for the London genomes. (B) Temporal signal in the tree. The signal was not strong enough to estimate the evolutionary rate, and instead the solid line represents the rate estimated in Fig. S1 based on the Sheffield data. Download
Data
Phylogenetic reconstruction of CC8 (excluding ST239). Branch color indicates MSSA (green) or MRSA (red). The symbols at branch tips indicate the geographic origins of these isolates. Close-ups of the two SCCmec IV clusters show their starlike radiation. SCCmec IV subtypes are shown. The third cluster represents USA300 isolates consisting of two ref...
Data
MRSA or MSSA genome size. The bar chart shows the average number of ncHGs per MSSA or MRSA isolate, respectively, excluding the HGs associated with SCCmec, for each major lineage. Asterisks indicate lineages with a significant size difference of the accessory genome in MSSA and MRSA isolates. CC8, P = 0.039; CC5, P = 0.0325 (statistically significa...
Data
Affiliations of and contact information for members of the European SRL Working Group.
Data
Prophage distribution. Rooted neighbor-joining tree like that in Fig. 1. Colors of branches indicate MSSA (green) and MRSA (red). Each isolate is annotated for affiliation to CCs or STs (A), SSCmec type and MSSA (green) or MRSA (red) (B), and seven prophage types classified on the basis of the presence or absence of their integrase genes (C). Color...
Data
Known genetic mechanisms of antibiotic resistance in S. aureus used to predict genotypic resistance.
Data
Phylogenetic reconstruction of CC15. Starlike phylogeny indicates the recent rapid expansion of this MSSA-only lineage. Symbols at the tips indicate the geographic origins of these isolates. The branch leading to an ST582 isolate—a single-locus variant of CC15—is shortened, and the number of SNPs defining that branch is shown. Download
Data
Number of ncHGs per major lineage. The bar chart shows the average number of ncHGs per isolate split into MGE type for each of the six major lineages. Each pie chart indicates the proportion of MGE types for each major lineage. Download
Data
Appendix: Walkthrough of web application for genomic pathogen surveillance. Download
Data
Phylogenetic reconstruction of CC45. Branch color indicates MSSA (green) or MRSA (red). The symbols at branch tips indicate the geographic origins of these isolates. SCCmec IV subtypes are shown. Download
Data
(A) Phylogenetic reconstruction of ST239 isolates in the sample. Red branches depict all of the MRSA isolates. The symbols at the tips of the branches indicate the geographic origins of the isolates. Isolates carrying the sasX gene are indicated by the letter X. Blue shading highlights isolates belonging to the Asian clade according to Harris et al...
Article
Full-text available
The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a UK MRSA database containing over 1,000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ir...
Article
Full-text available
Melioidosis is a tropical disease of high mortality caused by the environmental bacterium, Burkholderia pseudomallei. We have collected clinical isolates from the highly endemic Northern Territory of Australia routinely since 1989, and animal and environmental B. pseudomallei isolates since 1991. Here we provide a complete record of all B. pseudoma...
Article
Full-text available
After heavy rains and flooding during early 2011 in the normally arid interior of Australia, melioidosis was diagnosed in 6 persons over a 4-month period. Although the precise global distribution of the causal bacterium Burkholderia pseudomallei remains to be determined, this organism can clearly survive in harsh and even desert environments outsid...
Article
Full-text available
Burkholderia pseudomallei isolates with shared multilocus sequence types (STs) have not been isolated from different continents. We identified two STs shared between Australia and Cambodia. Whole-genome analysis revealed substantial diversity within STs, correctly identified the Asian or Australian origin, and confirmed that these shared STs were d...
Conference Paper
Full-text available
Since the first detection of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the late 1980s, a single clone, designated as USA300, has been responsible for an ongoing CA-MRSA epidemic in the United States. The understanding of the emergence and transmission of hospital-acquired MRSA (HA-MRSA) has made great process dur...
Article
Full-text available
Previously, we have described the development of the generic mobile phone data gathering tool, EpiCollect, and an associated web application, providing two-way communication between multiple data gatherers and a project database. This software only allows data collection on the phone using a single questionnaire form that is tailored to the needs o...
Article
Full-text available
Burkholderia pseudomallei is a Gram-negative soil bacillus that is the etiological agent of melioidosis and a biothreat agent. Little is known about the biogeography of this bacterium in Australia, despite its hyperendemicity in the northern region of this continent. The population structure of 953 Australian B. pseudomallei strains representing 77...
Article
Full-text available
Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a m...
Article
Full-text available
Two cases of melioidosis at a residence in rural northern Australia were linked to the unchlorinated domestic bore (automated well) water supply, which was found to have a high concentration of Burkholderia pseudomallei. Using multilocus sequence typing, clinical B. pseudomallei isolates from both cases were identical to an isolate from the bore wa...
Article
Full-text available
In the tropical city of Darwin, Northern Territory, Australia, dry season soil sampling cultured Burkholderia pseudomallei from 7 (70%) of 10 sports fields. However, during the 23 years of the Darwin Prospective Melioidosis Study, only 5 (0.6%) of 785 melioidosis cases have been attributed to infection from sports fields. In one soccer player with...
Article
Full-text available
Objective: We sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients. Design: Prospective cohort study. Setting: Orange County, California. Participants: Thirty hospitals in a single county. Methods: We collected clinical MRSA isolates...
Article
Full-text available
There is a need for a regional assessment of the frequency and diversity of MRSA to determine major circulating clones and the extent to which community and healthcare MRSA reservoirs have mixed. We conducted a prospective cohort study of inpatients in Orange County, California, systematically collecting clinical MRSA isolates from 30 hospitals, to...
Data
spa type frequencies by hospital for the 2,246 clinical MRSA isolates collected from 30 hospitals in Orange County, CA. (DOCX)
Article
Full-text available
We assessed characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among residents of 22 nursing homes. Of MRSA-positive swabs, 25% (208/824) were positive for CA-MRSA. Median facility CA-MRSA percentage was 22% (range, 0%-44%). In multivariate models, carriage was associated with age les...
Article
Full-text available
The available Leptospira multilocus sequence typing (MLST) scheme supported by a MLST website is limited to L. interrogans and L. kirschneri. Our aim was to broaden the utility of this scheme to incorporate a total of seven pathogenic species. We modified the existing scheme by replacing one of the seven MLST loci (fadD was changed to caiB), as the...
Data
Serovars within individual sequence types (STs). (DOC)
Data
Sequence types (STs) within individual serovars. (DOC)
Data
Phylogenetic tree of L. interrogans. A neighbor-joining tree was constructed from concatenated sequences of the 7 MLST loci for 111 unique STs of L. interrogans. Colored triangles refer to clonal complexes (CC) as defined by eBURST. Red is for CC 37, and blue is for CC 12. The largest cluster contains isolates with a global distribution. The three...
Data
List of Leptospira spp. used in this study. (DOC)
Data
Maximum likelihood tree based on concatenated sequences of 6 MLST loci, excluding tpiA. All of the L. weilii isolates resided in only two lineages, resolving the apparently polyphyletic nature of this species. Color code: khaki, L. interrogans; dark blue, L. kirschneri; pink, L. nogouchii; dark green, L. santarosai; light green, L. borgpetersenii;...
Data
Accession numbers for rrs fragments sequenced in this study. (DOC)
Data
dN/dS ratio of each MLST locus for 7 Leptospira species. (DOC)
Article
Full-text available
The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drugresistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health c...
Conference Paper
Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have caused healthcare-associated infection in single hospitals. It is unknown whether CA-MRSA has uniformly penetrated hospitals or if variation exists. Identifying hospital characteristics associated with higher penetration may inform infection control...
Conference Paper
Background: The prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is rising in hospitals, but the extent of CA-MRSA penetration into nursing homes has not been well-studied. CA-MRSA, particularly the USA300 strain, may cause increased transmission and more serious clinical disease than traditional healthcare s...
Article
Full-text available
Streptococcus pyogenes M/emm3 strains have been epidemiologically linked with enhanced infection severity and risk of streptococcal toxic shock syndrome (STSS), a syndrome triggered by superantigenic stimulation of T cells. Comparison of S. pyogenes strains causing STSS demonstrated that emm3 strains were surprisingly less mitogenic than other emm-...
Data
Cytokine levels in thigh tissue homogenate from superantigen-sensitive HLA-DQ8 mice infected with GAS-M3smeZ-M89 (White box-whisker) or GAS-M3smeZ-M3 (Grey box-whisker). Five mice per group were infected intramuscularly and after 24 hours infected tissue was removed and homogenated in sterile PBS. Cytokines were measured using Luminex®. Dotted hori...
Data
Bacterial colony forming units in spleen and liver following intramuscular infection with 7 different emm -types of S. pyogenes. (DOCX)
Data
Superantigen profile of each STSS isolate determined by PCR. (DOCX)
Data
Cytokine levels in serum from superantigen-sensitive DQ8 mice infected with GAS-M3smeZ-M89 (White box-whisker) or GAS-M3smeZ-M3 (Grey box-whisker). Five mice per group were infected intramuscularly and after 24 hours blood was removed by cardiac puncture. Cytokines were measured using Luminex®. Dotted horizontal line; lowest detectable level of eac...
Article
Full-text available
Hospital-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health burden dominated by a small number of bacterial clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals for 20 y, but its evolutionary origin and the molecular basis for its hospital association are unclear. We c...
Article
Full-text available
Multilocus sequence 18 typing (MLST) is a sequence-based genotyping method based on polymorphisms (each variant is termed an allele) in seven housekeeping genes (loci) (arcC, aroE, glpF, gmk, pta, tpi, and yqiL) in Staphylococcus aureus, providing unique allelic profiles known as sequence types (STs) (1).
Article
In this review, based on my Garrod Lecture to the British Society for Antimicrobial Chemotherapy, I have given a brief outline of my career over the past 40 years, starting with research in the 1970s into the properties and functions of penicillin-binding proteins (PBPs), leading to the identification of the high molecular mass PBPs as the physiolo...
Article
Full-text available
Rates of hospital-acquired infections, specifically methicillin-resistant Staphylococcus aureus (MRSA), are increasingly being used as indicators for quality of hospital hygiene. There has been much effort on understanding the transmission process at the hospital level; however, interhospital population-based transmission remains poorly defined. We...