Scarlet Fever

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Mark R Davies - One of the best experts on this subject based on the ideXlab platform.

  • Scarlet Fever epidemic in china caused by streptococcus pyogenes serotype m12 epidemiologic and molecular analysis
    EBioMedicine, 2018
    Co-Authors: Yuanhai You, Mark R Davies, Liam Mcintyre, Mark Walker, Melinda M Protani, Jianzhong Zhang
    Abstract:

    Abstract From 2011, Hong Kong and mainland China have witnessed a sharp increase in reported cases, with subsequent reports of epidemic Scarlet Fever in North Asia and the United Kingdom. Here we examine epidemiological data and investigate the genomic context of the predominantly serotype M12 Streptococcus pyogenes Scarlet Fever isolates from mainland China. Incident case data was obtained from the Chinese Nationwide Notifiable Infectious Diseases Reporting Information System. The relative risk of Scarlet Fever in recent outbreak years 2011–2016 was calculated using the median age-standardised incidence rate, compared to years 2003–2010 prior this outbreak. Whole genome sequencing was performed on 32 emm12 Scarlet Fever isolates and 13 emm12 non-Scarlet Fever isolates collected from different geographic regions of China, and compared with 203 published emm12 S. pyogenes genomes predominantly from Scarlet Fever outbreaks in Hong Kong (n = 134) and the United Kingdom (n = 63). We found during the outbreak period (2011–2016), the median age-standardised incidence in China was 4.14/100,000 (95% confidence interval (CI) 4.11-4.18), 2.62-fold higher (95% CI 2.57-2.66) than that of 1.58/100,000 (95% CI 1.56-1.61) during the baseline period prior to the outbreak (2003 − 2010). Highest incidence was reported for children 5 years of age (80.5/100,000). Streptococcal toxin encoding prophage φHKU.vir and φHKU.ssa in addition to the macrolide and tetracycline resistant ICE-emm12 and ICE-HKU397 elements were found amongst mainland China multi-clonal emm12 isolates suggesting a role in selection and expansion of Scarlet Fever lineages in China. Global dissemination of toxin encoded prophage has played a role in the expansion of Scarlet Fever emm12 clones. These findings emphasize the role of comprehensive surveillance approaches for monitoring of epidemic human disease.

  • Dendrogram of the intergenic region of the covR gene identified within 64 GAS genome sequences.
    2018
    Co-Authors: Sean J. Buckley, Mark R Davies, Peter Timms, David J. Mcmillan
    Abstract:

    Bootstrap values (percentage from 1000 replicates) of greater than 40% are shown at the bifurcating nodes. emm-pattern (A-C, D, and E) and disease associations are also shown. ARF/RHD = acute rheumatic Fever/ rheumatic heart disease, PSGN = post streptococcal glomerulonephritis, SF = Scarlet Fever, PH = pharyngitis, COM = asymptomatic community, O = other, and U = unknown.

  • Dendrogram of concatenated variation in the upstream intergenic region of two-component systems within 64 reference GAS genomes.
    2018
    Co-Authors: Sean J. Buckley, Mark R Davies, Peter Timms, David J. Mcmillan
    Abstract:

    The tree was constructed using concatenated sequences of the polymorphic nucleotide of all 14 TCS IGR regions. Bootstrap values (percentage from 1000 replicates) of greater than 40% are shown at the bifurcating nodes. Disease and emm-pattern association are also shown. ARF = acute rheumatic Fever, PSGN = post streptococcal glomerulonephritis, Scarlet = Scarlet Fever, Community = asymptomatic carriage.

  • transfer of Scarlet Fever associated elements into the group a streptococcus m1t1 clone
    Scientific Reports, 2015
    Co-Authors: Nouri Ben L Zakour, Mark R Davies, Yuanhai You, Jonathan H K Chen, Brian M Forde, Mitchell Stantoncook, Ruifu Yang, Yujun Cui, Timothy C Barnett
    Abstract:

    The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of Scarlet Fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of Scarlet Fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 Scarlet Fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

  • emergence of Scarlet Fever streptococcus pyogenes emm12 clones in hong kong is associated with toxin acquisition and multidrug resistance
    Nature Genetics, 2015
    Co-Authors: Nouri Ben L Zakour, Mark R Davies, Timothy C Barnett, Matthew T G Holden, Paul Coupland, Jonathan Hon Kwan Chen, Carola Venturini, Herman Tse
    Abstract:

    A Scarlet Fever outbreak began in mainland China and Hong Kong in 2011 (refs. 1-6). Macrolide- and tetracycline-resistant Streptococcus pyogenes emm12 isolates represent the majority of clinical cases. Recently, we identified two mobile genetic elements that were closely associated with emm12 outbreak isolates: the integrative and conjugative element ICE-emm12, encoding genes for tetracycline and macrolide resistance, and prophage ΦHKU.vir, encoding the superantigens SSA and SpeC, as well as the DNase Spd1 (ref. 4). Here we sequenced the genomes of 141 emm12 isolates, including 132 isolated in Hong Kong between 2005 and 2011. We found that the introduction of several ICE-emm12 variants, ΦHKU.vir and a new prophage, ΦHKU.ssa, occurred in three distinct emm12 lineages late in the twentieth century. Acquisition of ssa and transposable elements encoding multidrug resistance genes triggered the expansion of Scarlet Fever-associated emm12 lineages in Hong Kong. The occurrence of multidrug-resistant ssa-harboring Scarlet Fever strains should prompt heightened surveillance within China and abroad for the dissemination of these mobile genetic elements.

Timothy C Barnett - One of the best experts on this subject based on the ideXlab platform.

  • prophage exotoxins enhance colonization fitness in epidemic Scarlet Fever causing streptococcus pyogenes
    Nature Communications, 2020
    Co-Authors: Stephan Brouwer, Timothy C Barnett, Liam Mcintyre, Johanna Richter, Katherine J Kasper, David M P De Oliveira, Tania Riverahernandez, Amanda J Cork, Magnus G Jespersen, B Schulz
    Abstract:

    The re-emergence of Scarlet Fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause Scarlet Fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of Scarlet Fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.

  • prophage exotoxins enhance colonization fitness in epidemic Scarlet Fever causing streptococcus pyogenes
    bioRxiv, 2020
    Co-Authors: Stephan Brouwer, Timothy C Barnett, Liam Mcintyre, Katherine J Kasper, David M P De Oliveira, Tania Riverahernandez, Amanda J Cork, Magnus G Jespersen, Johanna Richter
    Abstract:

    The re-emergence of Scarlet Fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause Scarlet Fever has been linked epidemiologically to the presence of novel prophages, including prophage {Phi}HKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here we report the comprehensive molecular characterization of {Phi}HKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for optimal growth in human blood, confers resistance to neutrophil killing, and degrades neutrophil extracellular traps (NETs). Investigating single, double and triple isogenic knockout mutants of the {Phi}HKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the etiology and pathogenesis of Scarlet Fever-causing GAS mediated by phage {Phi}HKU.vir exotoxins.

  • detection of epidemic Scarlet Fever group a streptococcus in australia
    Clinical Infectious Diseases, 2019
    Co-Authors: Mark J Walker, Brian M Forde, Timothy C Barnett, Stephan Brouwer, Kate A Worthing, Liam Mcintyre, Lana Sundac, Sam Maloney, Leah W Roberts, Johanna Richter
    Abstract:

    Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing Scarlet Fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 Scarlet Fever isolate related to United Kingdom outbreak strains. National surveillance to monitor this pandemic is recommended.

  • detection of epidemic Scarlet Fever group a streptococcus in australia
    Clinical Infectious Diseases, 2019
    Co-Authors: Mark Walker, Brian M Forde, Timothy C Barnett, Stephan Brouwer, Kate A Worthing, Liam Mcintyre, Lana Sundac, Sam Maloney, Leah W Roberts, Johanna Richter
    Abstract:

    Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing Scarlet Fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 Scarlet Fever isolate related to UK outbreak strains. National surveillance to monitor this pandemic is recommended.

  • transfer of Scarlet Fever associated elements into the group a streptococcus m1t1 clone
    Scientific Reports, 2015
    Co-Authors: Nouri Ben L Zakour, Mark R Davies, Yuanhai You, Jonathan H K Chen, Brian M Forde, Mitchell Stantoncook, Ruifu Yang, Yujun Cui, Timothy C Barnett
    Abstract:

    The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of Scarlet Fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of Scarlet Fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 Scarlet Fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

Max Pearson - One of the best experts on this subject based on the ideXlab platform.

  • emergence of dominant toxigenic m1t1 streptococcus pyogenes clone during increased Scarlet Fever activity in england a population based molecular epidemiological study
    Lancet Infectious Diseases, 2019
    Co-Authors: Nn Lynskey, Claire E. Turner, Elita Jauneikaite, Xiangyun Zhi, Mia Mosavie, Max Pearson
    Abstract:

    Summary Background Since 2014, England has seen increased Scarlet Fever activity unprecedented in modern times. In 2016, England's Scarlet Fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events. Methods We analysed changes in S pyogenes emm genotypes, and notifications of Scarlet Fever and invasive disease in 2014–16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009–16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as Scarlet Fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses. Findings Coincident with national increases in Scarlet Fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p Interpretation A dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance. Funding UK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.

  • emergence of dominant toxigenic m1t1 streptococcus pyogenes clone during increased Scarlet Fever activity in england a population based molecular epidemiological study
    Social Science Research Network, 2019
    Co-Authors: Nn Lynskey, Claire E. Turner, Elita Jauneikaite, Xiangyun Zhi, Mia Mosavie, Max Pearson, Masanori Asai, Ludmila Lobkowicz, Yimmy J. Chow
    Abstract:

    Background:  England is experiencing Scarlet Fever activity unprecedented in modern times. In 2016, England's Scarlet Fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular-epidemiological investigation of these events and emergence of a new emm1 lineage.   Methods: We analysed changes in S. pyogenes emm-genotypes, and notifications of Scarlet Fever and invasive disease 2014-2016 using regional and national data. We analysed genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-2016, and compared 2800 global emm1 sequences. Expression of Streptococcal pyrogenic exotoxin (Spe)A by sequenced non-invasive emm1 isolates was quantified. Findings: Coincident with national increases in Scarlet Fever and invasive disease, emm1 S. pyogenes infections increased significantly, accounting for 32·6% (47/144) of pharyngeal isolates in North West London and 41·9% (267/637) of invasive isolates nationally in March-May 2016. Sequences of emm1 isolates from 2009-2016 demonstrated emergence of a new emm1 lineage (M1UK), with overlap of pharyngitis, Scarlet Fever, and invasive M1UK strains, that could be genotypically distinguished from pandemic emm1 isolates (M1global). Compared with M1global , median expression of SpeA increased 9-fold in M1UK isolates. M1UK expanded nationally to represent 84% (252/299) of all emm1, genomes in 2016; analysis identified two M1UK isolates outside the UK. Interpretation: A dominant new emm1 S. pyogenes lineage characterized by increased SpeA production has emerged during increased S. pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S. pyogenes provide plausible explanation for increased invasive disease, and rationale for global surveillance. Funding Statement: Supported by grants from Medical Research Council (MR/P022669/1); NIHR Health Protection Unit in AMR and HCAI (HPRU-2012-10047); NIHR BRC SpyVAC; Conor Kerin Foundation. NNL is a Sir Henry Wellcome Postdoctoral Research Fellow funded by the Wellcome Trust (103197/Z/13/Z); EJ is a Rosetrees/Stoneygate 2017 Imperial College Research Fellow (M683). Declaration of Interests: JP is a consultant to Next Gen Diagnostics LLC; other authors declare no interests. Ethics Approval Statement: Clinical data were linked to isolates and anonymized in accordance with Research Ethics approval 06/Q0406/20.

Elita Jauneikaite - One of the best experts on this subject based on the ideXlab platform.

  • high frequency transmission asymptomatic shedding and airborne spread of streptococcus pyogenes among schoolchildren exposed to Scarlet Fever a longitudinal multi cohort moleculo epidemiological contact tracing study
    medRxiv, 2021
    Co-Authors: Rebecca Cordery, Derren Ready, Elita Jauneikaite, Mia Mosavie, Amrit Purba, Lipi Begum, Ewurabena Mills, A R Vieira, Rhoda C Y Leung, Peter Hoffman
    Abstract:

    Background: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, Scarlet Fever outbreaks increased in England between 2014-2018. Methods: We undertook a prospective, intensive contact tracing study in schools with consecutive Scarlet Fever cases to assess the impact of standard interventions on transmission of Streptococcus pyogenes between cases, classroom contacts, households, and classroom environments over 4 weeks using genome sequencing. Findings: Six classes, comprising 12 Scarlet Fever cases, 17 household contacts, and 278 classroom contacts were recruited. Prevalence of the outbreak strain in asymptomatic classroom contacts was high, increasing from 9.6% in week 1, to 26.9% in week 2, 23.9% in week 3, then 14.3% in week 4. Colonisation with non-outbreak strains was 0 - 7.5%. Genome sequencing showed clonality of isolates within each of six classes, confirming recent transmission accounted for high carriage. Of asymptomatic classroom contacts with S. pyogenes-positive throat swabs who were tested for transmissibility, 6/28 (21%) had positive cough plates and/or hand swabs, of whom three remained S. pyogenes-positive for 3 weeks. Only 1/60 surface swabs taken in 3 classrooms yielded S. pyogenes. In contrast, settle plates placed in elevated locations were S. pyogenes-positive in both classrooms tested. Interpretation: S. pyogenes transmission in schools is intense and may occur prior to, or in spite of reported treatment of cases, underlining a need for rapid case management. Despite guideline adherence, heavy shedding of S. pyogenes by small numbers of classroom contacts may perpetuate outbreaks, and airborne transmission has a plausible role in spread.

  • emergence of dominant toxigenic m1t1 streptococcus pyogenes clone during increased Scarlet Fever activity in england a population based molecular epidemiological study
    Lancet Infectious Diseases, 2019
    Co-Authors: Nn Lynskey, Claire E. Turner, Elita Jauneikaite, Xiangyun Zhi, Mia Mosavie, Max Pearson
    Abstract:

    Summary Background Since 2014, England has seen increased Scarlet Fever activity unprecedented in modern times. In 2016, England's Scarlet Fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events. Methods We analysed changes in S pyogenes emm genotypes, and notifications of Scarlet Fever and invasive disease in 2014–16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009–16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as Scarlet Fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses. Findings Coincident with national increases in Scarlet Fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p Interpretation A dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance. Funding UK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.

  • emergence of dominant toxigenic m1t1 streptococcus pyogenes clone during increased Scarlet Fever activity in england a population based molecular epidemiological study
    Social Science Research Network, 2019
    Co-Authors: Nn Lynskey, Claire E. Turner, Elita Jauneikaite, Xiangyun Zhi, Mia Mosavie, Max Pearson, Masanori Asai, Ludmila Lobkowicz, Yimmy J. Chow
    Abstract:

    Background:  England is experiencing Scarlet Fever activity unprecedented in modern times. In 2016, England's Scarlet Fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular-epidemiological investigation of these events and emergence of a new emm1 lineage.   Methods: We analysed changes in S. pyogenes emm-genotypes, and notifications of Scarlet Fever and invasive disease 2014-2016 using regional and national data. We analysed genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009-2016, and compared 2800 global emm1 sequences. Expression of Streptococcal pyrogenic exotoxin (Spe)A by sequenced non-invasive emm1 isolates was quantified. Findings: Coincident with national increases in Scarlet Fever and invasive disease, emm1 S. pyogenes infections increased significantly, accounting for 32·6% (47/144) of pharyngeal isolates in North West London and 41·9% (267/637) of invasive isolates nationally in March-May 2016. Sequences of emm1 isolates from 2009-2016 demonstrated emergence of a new emm1 lineage (M1UK), with overlap of pharyngitis, Scarlet Fever, and invasive M1UK strains, that could be genotypically distinguished from pandemic emm1 isolates (M1global). Compared with M1global , median expression of SpeA increased 9-fold in M1UK isolates. M1UK expanded nationally to represent 84% (252/299) of all emm1, genomes in 2016; analysis identified two M1UK isolates outside the UK. Interpretation: A dominant new emm1 S. pyogenes lineage characterized by increased SpeA production has emerged during increased S. pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S. pyogenes provide plausible explanation for increased invasive disease, and rationale for global surveillance. Funding Statement: Supported by grants from Medical Research Council (MR/P022669/1); NIHR Health Protection Unit in AMR and HCAI (HPRU-2012-10047); NIHR BRC SpyVAC; Conor Kerin Foundation. NNL is a Sir Henry Wellcome Postdoctoral Research Fellow funded by the Wellcome Trust (103197/Z/13/Z); EJ is a Rosetrees/Stoneygate 2017 Imperial College Research Fellow (M683). Declaration of Interests: JP is a consultant to Next Gen Diagnostics LLC; other authors declare no interests. Ethics Approval Statement: Clinical data were linked to isolates and anonymized in accordance with Research Ethics approval 06/Q0406/20.

Nouri Ben L Zakour - One of the best experts on this subject based on the ideXlab platform.

  • transfer of Scarlet Fever associated elements into the group a streptococcus m1t1 clone
    Scientific Reports, 2015
    Co-Authors: Nouri Ben L Zakour, Mark R Davies, Yuanhai You, Jonathan H K Chen, Brian M Forde, Mitchell Stantoncook, Ruifu Yang, Yujun Cui, Timothy C Barnett
    Abstract:

    The group A Streptococcus (GAS) M1T1 clone emerged in the 1980s as a leading cause of epidemic invasive infections worldwide, including necrotizing fasciitis and toxic shock syndrome. Horizontal transfer of mobile genetic elements has played a central role in the evolution of the M1T1 clone, with bacteriophage-encoded determinants DNase Sda1 and superantigen SpeA2 contributing to enhanced virulence and colonization respectively. Outbreaks of Scarlet Fever in Hong Kong and China in 2011, caused primarily by emm12 GAS, led to our investigation of the next most common cause of Scarlet Fever, emm1 GAS. Genomic analysis of 18 emm1 isolates from Hong Kong and 16 emm1 isolates from mainland China revealed the presence of mobile genetic elements associated with the expansion of emm12 Scarlet Fever clones in the M1T1 genomic background. These mobile genetic elements confer expression of superantigens SSA and SpeC, and resistance to tetracycline, erythromycin and clindamycin. Horizontal transfer of mobile DNA conferring multi-drug resistance and expression of a new superantigen repertoire in the M1T1 clone should trigger heightened public health awareness for the global dissemination of these genetic elements.

  • emergence of Scarlet Fever streptococcus pyogenes emm12 clones in hong kong is associated with toxin acquisition and multidrug resistance
    Nature Genetics, 2015
    Co-Authors: Nouri Ben L Zakour, Mark R Davies, Timothy C Barnett, Matthew T G Holden, Paul Coupland, Jonathan Hon Kwan Chen, Carola Venturini, Herman Tse
    Abstract:

    A Scarlet Fever outbreak began in mainland China and Hong Kong in 2011 (refs. 1-6). Macrolide- and tetracycline-resistant Streptococcus pyogenes emm12 isolates represent the majority of clinical cases. Recently, we identified two mobile genetic elements that were closely associated with emm12 outbreak isolates: the integrative and conjugative element ICE-emm12, encoding genes for tetracycline and macrolide resistance, and prophage ΦHKU.vir, encoding the superantigens SSA and SpeC, as well as the DNase Spd1 (ref. 4). Here we sequenced the genomes of 141 emm12 isolates, including 132 isolated in Hong Kong between 2005 and 2011. We found that the introduction of several ICE-emm12 variants, ΦHKU.vir and a new prophage, ΦHKU.ssa, occurred in three distinct emm12 lineages late in the twentieth century. Acquisition of ssa and transposable elements encoding multidrug resistance genes triggered the expansion of Scarlet Fever-associated emm12 lineages in Hong Kong. The occurrence of multidrug-resistant ssa-harboring Scarlet Fever strains should prompt heightened surveillance within China and abroad for the dissemination of these mobile genetic elements.