288 results found
Reuter S, Torok ME, Holden MTG, et al., 2017, Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland (vol 26, pg 263, 2016), GENOME RESEARCH, Vol: 27, Pages: 1622-1622, ISSN: 1088-9051
Donker T, Reuter S, Scriberras J, et al., 2017, Population genetic structuring of methicillin-resistant Staphylococcus aureus clone EMRSA-15 within UK reflects patient referral patterns., Microbial Genomics, Vol: 3, ISSN: 2057-5858
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 the differences between bacterial populations of 52 hospitals in the United Kingdom and Ireland, using whole-genome sequences from 1085 MRSA clonal complex 22 isolates collected between 1998 and 2012. The genetic differences between bacterial populations were compared with the number of patients transferred between hospitals and their regional structure. The MRSA populations within single hospitals, regions and countries were genetically distinct from the rest of the bacterial population at each of these levels. Hospitals from the same patient referral regions showed more similar MRSA populations, as did hospitals sharing many patients. Furthermore, the bacterial populations from different time-periods within the same hospital were generally more similar to each other than contemporaneous bacterial populations from different hospitals. We conclude that, while a large part of the dispersal and expansion of MRSA takes place among patients seeking care in single hospitals, inter-hospital spread of resistant bacteria is by no means a rare occurrence. Hospitals are exposed to constant introductions of MRSA on a number of levels: (1) most MRSA is received from hospitals that directly transfer large numbers of patients, while (2) fewer introductions happen between regions or (3) across national borders, reflecting lower numbers of transferred patients. A joint coordinated control effort between hospitals, is therefore paramount for the national control of MRSA, antibiotic-resistant bacteria and other hospital-associated pathogens.
Chewapreecha C, Holden MTG, Vehkala M, et al., 2017, Global and regional dissemination and evolution of Burkholderia pseudomallei., Nat Microbiol, Vol: 2
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 an early reservoir, with transmission to Southeast Asia followed by onward transmission to South Asia and East Asia. Repeated reintroductions were observed within the Malay Peninsula and between countries bordered by the Mekong River. Our data support an African origin of the Central and South American isolates with introduction of B. pseudomallei into the Americas between 1650 and 1850, providing a temporal link with the slave trade. We also identified geographically distinct genes/variants in Australasian or Southeast Asian isolates alone, with virulence-associated genes being among those over-represented. This provides a potential explanation for clinical manifestations of melioidosis that are geographically restricted.
Argimón S, Abudahab K, Goater RJE, et al., 2016, Microreact: visualizing and sharing data for genomic epidemiology and phylogeography, Microbial Genomics, Vol: 2, ISSN: 2057-5858
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 system under investigation. Selected static images are then used within publications to highlight the key findings to a wider audience. However, these images are a very inadequate way of exploring and interpreting the richness of the data. There is, therefore, a need for flexible, interactive software that presents the population genomic outputs and associated data in a user-friendly manner for a wide range of end users, from trained bioinformaticians to front-line epidemiologists and health workers. Here, we present Microreact, a web application for the easy visualization of datasets consisting of any combination of trees, geographical, temporal and associated metadata. Data files can be uploaded to Microreact directly via the web browser or by linking to their location (e.g. from Google Drive/Dropbox or via API), and an integrated visualization via trees, maps, timelines and tables provides interactive querying of the data. The visualization can be shared as a permanent web link among collaborators, or embedded within publications to enable readers to explore and download the data. Microreact can act as an end point for any tool or bioinformatic pipeline that ultimately generates a tree, and provides a simple, yet powerful, visualization method that will aid research and discovery and the open sharing of datasets.
Price EP, MacHunter B, Spratt BG, et al., 2016, Improved multilocus sequence typing of Burkholderia pseudomallei and closely related species., Journal of Medical Microbiology, Vol: 65, Pages: 992-997, ISSN: 1473-5644
The Burkholderiapseudomallei 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 relatedness of B. pseudomallei and its nearest neighbours. Based on this analysis, we propose that the recently described B. pseudomallei complex (Bpc) should be expanded to encompass B. pseudomallei, Burkholderiahumptydooensis (proposed), Burkholderiamallei, Burkholderiaoklahomensis, Burkholderiathailandensis and three unassigned Burkholderia Clades A, B and C (represented by type strains BDU 5, BDU 8 and MSMB0265, respectively). Of note, the MLST narK locus is present in all Bpc species but is missing in all other Burkholderia spp., including all Burkholderiacepacia complex species, with the exception of most Burkholderiaubonensis strains, which contain narK but encode genetically distinct sequences. The presence of narK is thus indicative of a Bpc strain. Next, we revisited in silico the performance of the existing MLST primers, which prompted redesign of primers targeting the gmhD, lepA, lipA, narK and ndh loci to encompass genetic diversity among Bpc strains and to address amplification/sequencing issues. We show in silico and in vitro that the redesigned primers yield good-quality amplification and sequencing results for the gmhD, lepA, lipA, narK and ndh loci in Bpc species. These primers provide an alternative for amplification and sequencing of MLST loci in Bpc species in cases when poor-quality amplification or sequencing data are obtained using the original MLST primers.
Didelot X, Dordel J, Whittles LK, et al., 2016, Genomic analysis and comparison of two gonorrhoea outbreaks, mBio, Vol: 7, ISSN: 2150-7511
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 but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak.
Aanensen DM, Feil EJ, Holden MT, et al., 2016, Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive staphylococcus aureus in Europe., mBio, Vol: 7, ISSN: 2161-2129
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 visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http://www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) community-oriented database infrastructure and analysis tools. IMPORTANCE: The spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine whole-genome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context
Reuter S, Toeroek ME, Holden MTG, et al., 2016, Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland, Genome Research, Vol: 26, Pages: 263-270, ISSN: 1549-5469
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 United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.
Spratt BG, Anderson RM, 2015, Special feature on evolution and genetics in medicine, Proceedings of the Royal Society B: Biological Sciences, Vol: 282, ISSN: 0962-8452
Chapple SN, Price EP, Sarovich DS, et al., 2015, Burkholderia pseudomallei Genotype Distribution in the Northern Territory, Australia., American Journal of Tropical Medicine and Hygiene, Vol: 94, Pages: 68-72, ISSN: 1476-1645
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. pseudomallei multilocus sequence types (STs) found in the Northern Territory to date, and distribution maps of the eight most common environmental STs. We observed surprisingly restricted geographic distributions of STs, which is contrary to previous reports suggesting widespread environmental dissemination of this bacterium. Our data suggest that B. pseudomallei from soil and water does not frequently disperse long distances following severe weather events or by migration of infected animals.
Yip TW, Hewagama S, Mayo M, et al., 2015, Endemic Melioidosis in Residents of Desert Region after Atypically Intense Rainfall in Central Australia, 2011, Emerging Infectious Diseases, Vol: 21, Pages: 1038-1040, ISSN: 1080-6059
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 outside the wet tropics.
De Smet B, Sarovich DS, Price EP, et al., 2015, Whole-genome sequencing confirms that Burkholderia pseudomallei multilocus sequence types common to both Cambodia and Australia are due to homoplasy., Journal of Clinical Microbiology, Vol: 53, Pages: 323-326, ISSN: 1098-660X
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 due to homoplasy.
Aanensen DM, Huntley DM, Menegazzo M, et al., 2014, EpiCollect+: linking smartphones to web applications for complex data collection projects., F1000Res, Vol: 3, Pages: 199-199
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 of the user (including a single GPS point and photo per entry), whereas many applications require a more complex structure, allowing users to link a series of forms in a linear or branching hierarchy, along with the addition of any number of media types accessible from smartphones and/or tablet devices (e.g., GPS, photos, videos, sound clips and barcode scanning). A much enhanced version of EpiCollect has been developed (EpiCollect+). The individual data collection forms in EpiCollect+ provide more design complexity than the single form used in EpiCollect, and the software allows the generation of complex data collection projects through the ability to link many forms together in a linear (or branching) hierarchy. Furthermore, EpiCollect+ allows the collection of multiple media types as well as standard text fields, increased data validation and form logic. The entire process of setting up a complex mobile phone data collection project to the specification of a user (project and form definitions) can be undertaken at the EpiCollect+ website using a simple 'drag and drop' procedure, with visualisation of the data gathered using Google Maps and charts at the project website. EpiCollect+ is suitable for situations where multiple users transmit complex data by mobile phone (or other Android devices) to a single project web database and is already being used for a range of field projects, particularly public health projects in sub-Saharan Africa. However, many uses can be envisaged from education, ecology and epidemiology to citizen science.
McRobb E, Kaestli M, Price EP, et al., 2014, Distribution of <i>Burkholderia pseudomallei</i> in Northern Australia, a Land of Diversity, APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Vol: 80, Pages: 3463-3468, ISSN: 0099-2240
Hudson LO, Reynolds C, Spratt BG, et al., 2013, Diversity of methicillin-resistant staphylococcus aureus strains isolated from residents of 26 nursing homes in Orange County, California, European Journal of Clinical Microbiology, Vol: 51, Pages: 3788-3795, ISSN: 0722-2211
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 multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.
Hill AA, Mayo M, Kaestli M, et al., 2013, Short Report: Melioidosis as a Consequence of Sporting Activity, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 89, Pages: 365-366, ISSN: 0002-9637
McRobb E, Kaestli M, Mayo M, et al., 2013, Short Report: Melioidosis from Contaminated Bore Water and Successful UV Sterilization, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, Vol: 89, Pages: 367-368, ISSN: 0002-9637
Murphy CR, Hudson LO, Spratt BG, et al., 2013, Predictors of Hospitals with Endemic Community-Associated Methicillin-Resistant Staphylococcus aureus, Infection Control and Hospital Epidemiology, Vol: 34, Pages: 581-587, ISSN: 1559-6834
OBJECTIVE—We sought to identify hospital characteristics associated with communityassociatedmethicillin-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 from inpatients in 30 of 31 hospitals inOrange County, California, from October 2008 through April 2010. We characterized isolates byspa typing to identify CA-MRSA strains. Using California’s mandatory hospitalization data set,we identified hospital-level predictors of CA-MRSA isolation.RESULTS—CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital,the median percentage of CA-MRSA isolates was 46% (range, 14%–81%). In multivariatemodels, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3%decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001), hospitals withmore Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates frompatients with hospital-onset infection.CONCLUSIONS—Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates.There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSAin smaller hospitals with healthier but socially disadvantaged patient populations. Additionalresearch is needed to determine whether infection control strategies can be successful in targetingCA-MRSA influx.
Hudson LO, Murphy CR, Spratt BG, et al., 2013, Diversity of Methicillin-Resistant Staphylococcus aureus (MRSA) strains isolated from inpatients of 30 hospitals in Orange County, California, PLOS One, Vol: 8, ISSN: 1932-6203
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 assess MRSA diversity and distribution. All isolates were characterized by spa typing, with selective PFGE and MLST to relate spa types with major MRSA clones. We collected 2,246 MRSA isolates from hospital inpatients. This translated to 91/10,000 inpatients with MRSA and an Orange County population estimate of MRSA inpatient clinical cultures of 86/100,000 people. spa type genetic diversity was heterogeneous between hospitals, and relatively high overall (72%). USA300 (t008/ST8), USA100 (t002/ST5) and a previously reported USA100 variant (t242/ST5) were the dominant clones across all Orange County hospitals, representing 83% of isolates. Fifteen hospitals isolated more t008 (USA300) isolates than t002/242 (USA100) isolates, and 12 hospitals isolated more t242 isolates than t002 isolates. The majority of isolates were imported into hospitals. Community-based infection control strategies may still be helpful in stemming the influx of traditionally community-associated strains, particularly USA300, into the healthcare setting.
Holden MTG, Hsu L-Y, Kurt K, et al., 2013, A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic, Genome Research, Vol: 23, Pages: 653-664, ISSN: 1549-5469
The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant 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 care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.
Murphy CR, Hudson LO, Spratt BG, et al., 2013, Predicting High Prevalence of Community Methicillin-Resistant <i>Staphylococcus aureus</i> Strains in Nursing Homes, INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY, Vol: 34, Pages: 325-328, ISSN: 0899-823X
Boonsilp S, Thaipadungpanit J, Amornchai P, et al., 2013, A Single Multilocus Sequence Typing (MLST) scheme for seven athogenic Leptospira species, PLOS Neglected Tropical Diseases, Vol: 7, ISSN: 1935-2735
Background:The availableLeptospiramultilocus sequence typing (MLST) scheme supported by a MLST website is limited toL. interrogansandL. kirschneri. Our aim was to broaden the utility of this scheme to incorporate a total of seven pathogenicspecies.Methodology and Findings:We modified the existing scheme by replacing one of the seven MLST loci (fadDwas changedtocaiB), as the former gene did not appear to be present in some pathogenic species. Comparison of the original andmodified schemes using data forL. interrogansandL. kirschneridemonstrated that the discriminatory power of the twoschemes was not significantly different. The modified scheme was used to further characterize 325 isolates (L. alexanderi [n = 5], L. borgpetersenii[n = 34], L. interrogans [n = 222], L. kirschneri [n = 29], L. noguchii [n = 9], L. santarosai [n = 10], and L.weilii [n = 16]). Phylogenetic analysis using concatenated sequences of the 7 loci demonstrated that each speciescorresponded to a discrete clade, and that no strains were misclassified at the species level. Comparison between genotype and serovar was possible for 254 isolates. Of the 31 sequence types (STs) represented by at least two isolates, 18 STs included isolates assigned to two or three different serovars. Conversely, 14 serovars were identified that contained between 2 to 10 different STs. New observations were made on the global phylogeography ofLeptospira spp., and the utility of MLST in making associations between human disease and specific maintenance hosts was demonstrated.Conclusion:The new MLST scheme, supported by an updated MLST website, allows the characterization and species assignment of isolates of the seven major pathogenic species associated with leptospirosis.
Turner CE, Sommerlad M, McGregor K, et al., 2012, Superantigenic activity of emm3 Streptococcus pyogenes is abrogated by a conserved naturally occurring smeZ mutation, PLOS One, Vol: 7, ISSN: 1932-6203
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-types (emm1, emm12, emm18, emm28, emm87, emm89) both in vitro and in vivo, indicating poor superantigenic activity. We identified a 13bp deletion in the superantigen smeZ gene of all emm3 strains tested. The deletion led to a premature stop codon in smeZ, and was not present in other major emm-types tested. Expression of a functional non-M3-smeZ gene successfully enhanced mitogenic activity in emm3 S. pyogenes and also restored mitogenic activity to emm1 and emm89 S. pyogenes strains where the smeZ gene had been disrupted. In contrast, the M3-smeZ gene with the 13bp deletion could not enhance or restore mitogenicity in any of these S. pyogenes strains, confirming that M3-smeZ is non-functional regardless of strain background. The mutation in M3-smeZ reduced the potential for M3 S. pyogenes to induce cytokines in human tonsil, but not during invasive infection of superantigen-sensitive mice. Notwithstanding epidemiological associations with STSS and disease severity, emm3 strains have inherently poor superantigenicity that is explained by a conserved mutation in smeZ.
Spratt BG, 2012, The 2011 Garrod Lecture: From penicillin-binding proteins to molecular epidemiology, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 67, Pages: 1578-1588, ISSN: 0305-7453
McAdam PR, Templeton KE, Edwards GF, et al., 2012, Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant <i>Staphylococcus aureus</i>, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 9107-9112, ISSN: 0027-8424
Ke W, Huang SS, Hudson LO, et al., 2012, Patient sharing and population genetic structure of methicillin-resistant <i>Staphylococcus aureus</i>, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 6763-6768, ISSN: 0027-8424
Harris SR, Clarke IN, Seth-Smith HMB, et al., 2012, Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing, Nature Genetics, Vol: 44, Pages: 413-419, ISSN: 1546-1718
Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.
Hudson LO, Murphy CR, Spratt BG, et al., 2012, Differences in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Pediatric and Adult Patients from Hospitals in a Large County in California, Journal of Clinical Microbiology, Vol: 50, Pages: 573-579, ISSN: 1098-660X
Studies of U.S. epidemics of community- and health care-associated methicillin-resistant Staphylococcus aureus (MRSA) suggested differences in MRSA strains in adults and those in children. Comprehensive population-based studies exploring these differences are lacking. We conducted a prospective cohort study of inpatients in Orange County, CA, collecting clinical MRSA isolates from 30 of 31 Orange County hospitals, to characterize differences in MRSA strains isolated from children compared to those isolated from adults. All isolates were characterized by spa typing. We collected 1,124 MRSA isolates from adults and 159 from children. Annual Orange County population estimates of MRSA inpatient clinical cultures were 119/100,000 adults and 22/100,000 children. spa types t008, t242, and t002 accounted for 83% of all isolates. The distribution of these three spa types among adults was significantly different from that among children (χ2 = 52.29; P < 0.001). Forty-one percent of adult isolates were of t008 (USA300), compared to 69% of pediatric isolates. In multivariate analyses, specimens from pediatric patients, wounds, non-intensive care unit (ICU) wards, and hospitals with a high proportion of Medicaid-insured patients were significantly associated with the detection of t008 strains. While community- and health care-associated MRSA reservoirs have begun to merge, significant differences remain in pediatric and adult patient populations. Community-associated MRSA spa type t008 is significantly more common in pediatric patients.
Dale J, Price EP, Hornstra H, et al., 2011, Epidemiological Tracking and Population Assignment of the Non-Clonal Bacterium, Burkholderia pseudomallei, PLOS Neglected Tropical Diseases, Vol: 5, ISSN: 1935-2735
Rapid assignment of bacterial pathogens into predefined populations is an important first step for epidemiological tracking.For clonal species, a single allele can theoretically define a population. For non-clonal species such as Burkholderiapseudomallei, however, shared allelic states between distantly related isolates make it more difficult to identify populationdefining characteristics. Two distinct B. pseudomallei populations have been previously identified using multilocus sequencetyping (MLST). These populations correlate with the major foci of endemicity (Australia and Southeast Asia). Here, we usemultiple Bayesian approaches to evaluate the compositional robustness of these populations, and provide assignmentresults for MLST sequence types (STs). Our goal was to provide a reference for assigning STs to an established populationwithout the need for further computational analyses. We also provide allele frequency results for each population to enableestimation of population assignment even when novel STs are discovered. The ability for humans and potentiallycontaminated goods to move rapidly across the globe complicates the task of identifying the source of an infection oroutbreak. Population genetic dynamics of B. pseudomallei are particularly complicated relative to other bacterial pathogens,but the work here provides the ability for broad scale population assignment. As there is currently no independentempirical measure of successful population assignment, we provide comprehensive analytical details of our comparisons toenable the reader to evaluate the robustness of population designations and assignments as they pertain to individualresearch questions. Finer scale subdivision and verification of current population compositions will likely be possible withgenotyping data that more comprehensively samples the genome. The approach used here may be valuable for other nonclonalpathogens that lack simple group-defining genetic characteristics and provides a rap
Ahmed A, Thaipadungpanit J, Boonsilp S, et al., 2011, Comparison of Two Multilocus Sequence Based Genotyping Schemes for Leptospira Species, PLOS Neglected Tropical Diseases, Vol: 5, ISSN: 1935-2735
Background: Several sequence based genotyping schemes have been developed for Leptospira spp. The objective of thisstudy was to genotype a collection of clinical and reference isolates using the two most commonly used schemes andcompare and contrast the results.Methods and Findings: A total of 48 isolates consisting of L. interrogans (n = 40) and L. kirschneri (n = 8) were typed by the 7locus MLST scheme described by Thaipadungpanit et al., and the 6 locus genotyping scheme described by Ahmed et al.,(termed 7L and 6L, respectively). Two L. interrogans isolates were not typed using 6L because of a deletion of threenucleotides in lipL32. The remaining 46 isolates were resolved into 21 sequence types (STs) by 7L, and 30 genotypes by 6L.Overall nucleotide diversity (based on concatenated sequence) was 3.6% and 2.3% for 7L and 6L, respectively. The D value(discriminatory ability) of 7L and 6L were comparable, i.e. 92.0 (95% CI 87.5–96.5) vs. 93.5 (95% CI 88.6–98.4). The dN/dSratios calculated for each locus indicated that none were under positive selection. Neighbor joining trees werereconstructed based on the concatenated sequences for each scheme. Both trees showed two distinct groupscorresponding to L. interrogans and L. kirschneri, and both identified two clones containing 10 and 7 clinical isolates,respectively. There were six instances in which 6L split single STs as defined by 7L into closely related clusters. We noted twodiscrepancies between the trees in which the genetic relatedness between two pairs of strains were more closely related by7L than by 6L.Conclusions: This genetic analysis indicates that the two schemes are comparable. We discuss their practical advantagesand disadvantages.
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