Molecular Characterization of the 2011 Hong Kong Scarlet Fever Outbreak

Abstract

A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases resulted in the isolation of Streptococcus pyogenes emm12 with multiple antibiotic resistances. Phylogenetic analysis of 22 emm12 scarlet fever outbreak isolates, 7 temporally and geographically matched emm12 non-scarlet fever isolates, and 18 emm12 strains isolated during 2005-2010 indicated the outbreak was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16 and HKU30), coupled with diagnostic polymerase chain reaction assays, identified 2 mobile genetic elements distributed across the major lineages: a 64.9-kb integrative and conjugative element encoding tetracycline and macrolide resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1 strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to neutrophils and virulence in a humanized plasminogen murine model. However, in contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests that factors such as mobile genetic elements, environmental factors, and host immune status may have contributed to the 2011 scarlet fever outbreak.

Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence

“…This indicates that M23ND is a heterogeneous population with one dominant and stable genomic organization probably under selective pressure. The heterogeneity in virulent strains has been reported in an epidemic GAS strain M12-HKU (Tse et al, 2012) and a b-lactam antibiotic resistant Staphylococcus aureus strain Mu50 (Cui et al, 2012). We note that we were unable to isolate a single living colony with any recombination event reverted.…”

“…Specifically, the repositioning of the virulence genes viz., sfb1, nga, slo and prtS allowed their clustering with speB, the mga regulon, and the hasABC operon, the appropriate regulation of which is indispensable for the virulence of S. pyogenes strains. Similar relocations of prtS, which are essential for resistance to neutrophil killing, were also induced from inversions in strains causing epidemic outbreaks or severe diseases, viz., M12-HKU16 (Tse et al, 2012), M3-SSI-1 (Nakagawa et al, 2003) and M5-Manfredo (Holden et al, 2007). Those observations indicate that the replication-and transcription-associated chromosomal rearrangements are dependent on the bacterial phenotypes or host infectious niches, and may signify recently emergent events.…”

“…The availability of complete genomic information of a variety of S. pyogenes strains makes it possible to carry out genomic-scale comparisons. Numerous studies revealed that the genomic structures of S. pyogenes are highly syntenic among different strains, except for M12-HKU16 (Tse et al, 2012), M5-Manfredo (Holden et al, 2007) and M3-SSI-1 (Nakagawa et al, 2003), all of which contain an X-shaped inversion (or X-alignment) that is symmetric around the replication axis, ori/ter. These inversions are mediated by homologous sequences, such as transposons (Tse et al, 2012) or rRNA-comX, the latter comprising an rRNA operon and the competence gene, comX (Holden et al, 2007;Nakagawa et al, 2003).…”

“…Numerous studies revealed that the genomic structures of S. pyogenes are highly syntenic among different strains, except for M12-HKU16 (Tse et al, 2012), M5-Manfredo (Holden et al, 2007) and M3-SSI-1 (Nakagawa et al, 2003), all of which contain an X-shaped inversion (or X-alignment) that is symmetric around the replication axis, ori/ter. These inversions are mediated by homologous sequences, such as transposons (Tse et al, 2012) or rRNA-comX, the latter comprising an rRNA operon and the competence gene, comX (Holden et al, 2007;Nakagawa et al, 2003). This type of symmetric inversion is not uncommon and has been analogously observed in organisms from multiple lineages (Eisen et al, 2000), including Salmonella (Liu & Sanderson, 1995), Chlamydia (Read et al, 2000) and Helicobacter (Zawilak et al, 2001).…”

Re-emergence of scarlet fever: old players return?

“…During the past decade, major outbreaks have been reported in Vietnam (over 23,000 cases in 2009), mainland China (>100,000 cases reported by the Chinese Ministry of Health), Hong Kong (>1000 cases, while before 2011 only sporadic cases were reported with the last major peak of 126 cases in 1976), and in the United Kingdom [8][9][10][11][12]. With 17,586 cases reported in 2015 and 7799 cases reported to Public Health England in 2016, until April 8 (Health Protection Report, Volume 10 Number 14), this is the biggest outbreak in this country since 1969; at that time, there were 16,093 new cases followed by a long disease-free period [8].…”