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Streptococcus Genomes Expose Features in Throat, Skin Infection-Causing Pathogens

NEW YORK (GenomeWeb) – A team led by researchers at the Lebanese American University has taken a genomic look at the forms of Streptococcus pyogenes involved in skin or throat infections in that country.

"[A]s [Group A Streptococcus] remains an important cause of diseases in Lebanon and in the world, studying its functional genomics could help in better understanding the molecular mechanisms and epidemiology of its pathogenesis," senior author Sima Tokajian, a natural sciences researcher at LAU, and co-authors of the PLOS One study wrote. "Our findings add value to epidemiological studies of S. pyogenes, and provide the first such study for Lebanese isolates."

The researchers did genome sequencing on nine Lebanese isolates of skin infection- or pharyngitis-associated S. pyogenes, a human pathogen also known as Group A Streptococcus (GAS). By comparing the genomes to one another and to sequences from other isolates around the world, they explored relationships between isolates, along with genome features related to virulence, antibiotic resistance, and other clinical features in S. pyogenes.

"Despite its limited prevalence in modern times as compared to other pathogens, the myriad of infections [S. pyogenes] causes are still commonly lethal," the authors explained, noting that these infections "range from localized throat infections such as tonsillitis or pharyngitis, to invasive infections such as sepsis, necrotizing fasciitis, and streptococcal toxic shock syndrome."

Using Illumina sequencing, the team tackled nine isolates obtained from one- to 48-year-old individuals with S. pyogenes infections in Lebanon, generating bacterial genome sequences that were assembled de novo for each isolate. The resulting genomes spanned between 1.7 million and almost 2 million bases, were covered to an average depth of 293-fold, and contained anywhere from almost 1,700 to more than 1,900 predicted protein-coding genes.

When they took a closer look at the nature of these genes, the researchers found that roughly one-fifth of each genome, on average, coded for genes related to virulence or defense. They examined those virulence factors — as well as antibiotic resistance sequences, gene regulatory features, recombination, and other clinically relevant S. pyogenes traits — in more detail in the isolates.

The team reported that all nine of the newly sequenced S. pyogenes isolates contained sequences coding for an ABC transporter membrane-spanning permease enzyme implicated in resistance to macrolide antibiotics, as well as two types of fluorquinolone antibiotic resistance factors, for example. The genomes from at least two of the isolates revealed features linked to tetracycline resistance and multi-drug resistance.

The team's multi-locus sequence typing experiments uncovered a range of S. pyogenes sequence types, though sites where isolates originated roughly coincided with so-called emm gene epidemiological marker types. 

With a phylogenetic analysis that focused on 40 gene families and included eight S. pyogenes reference strains, the researchers explored relationships between the Lebanese strains and S. pyogenes isolates sequenced previously. In particular, they noted that the isolates involved in skin and throat infections in Lebanon did not fall into one phylogenetic cluster, but were instead peppered across the S. pyogenes tree depending on their geographic origin and associated clinical symptoms.

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