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  • The human-associated clade of S. suis.

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The human-associated clade of S. suis.
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The human-associated clade of S. suis.

bioxone June 23, 2021June 22, 2021

Hari Krishnan R, SRM Institute of Science and Technology

Many of the fatal infectious diseases caused in humans are “zoonotic”, which means they are transmitted from animals to humans via their consumption or being in close contact. Various human pathogens are yet to be identified which would have the potential to initiate another pandemic, probably worse than the current COVID-19 pandemic. For the past 3 decades, scientists are working on a pig colonizing bacteria Streptococcus suis, which are capable of causing deadly human infections like septicemia and meningitis. The past three decades have witnessed 3 outbreaks of S. suis in China (1998, 2005, and 2016). The 2005 outbreak was deadly as it affected more than 200 people with a mortality rate of 20%. The genetics of this bacteria and how it is associated with human diseases were unknown, until recently, where a group of Chinese scientists discovered a novel human-associated clade (HAC) diversified from S. suis. 

What is HAC?

A human-associated clade (HAC) is a novel group of S. suis variants that are strongly linked with human infections. It is evolving as a high-risk human pathogen as experimental studies on animal models show evidence of it being highly virulent and lethal. 

Phylogenomic analysis of 1634 isolates from 14 countries identified Western Europe as the origin of the human-associated clade. It is also evident that the spread to Asian countries probably happened due to the export of European swine breeds in the 1960s. HAC’s isolated from healthy pigs showed high virulence thereby suggesting that healthy pigs could be the carrier for human transmissions.

Human-associated clade Lineages and accessory genes

HAC has been further classified into 3 sub-lineages namely, I, II, and III. Lineage I and III are highly virulent ones that are specific to the China isolates. The two outbreaks in 1998 and 2005 in Jiangsu and Sichuan, respectively, were associated with Lineage I. It is also known to contain an 89kb large pathogenicity island (PAI) which allows them to adapt to various host environments. 

Lineage II is associated with China and Vietnam variants that emerged in the 1960s. This variant was isolated from the recent 2016 outbreak in China and was found to be highly virulent. This lineage also contains a 79kb long pathogenicity island (PAI) which expresses genes that are responsible for the virulence factor. Around 46 genes have been identified that are linked to Lineage II, of which 39 are located in the PAI. Lineage I and II are thought to have evolved from independent routes between the 2005 outbreak (Lineage I) and the 2016 outbreak (Lineage 2).

Lineage III is a novel type that probably emerged from the UK. These variants lack pathogenicity island (PAI) but are capable of expressing around 8 antibiotic resistance genes including tetracycline. Around 69 Lineage III specific genes have also been identified that are located within a mobile genetic element (MGE) and codes for all antibiotic resistance genes.

HAC-Specific Virulence Genes

There are almost 66 HAC-specific genes identified out of which around 25 core genes have been linked to virulence. The important virulence factor genes are pnuC, epf, and nadR. 

  • pnuC plays a role in the nucleotide salvage pathway and it helps in overcoming in oxidative stress tolerance of S. suis during infection.
  • The EPF gene was found to be expressed in patients with S. suis infection from Thailand. This gene is known to be highly virulent. 
  • nadR is a transcription factor regulating the virulence of S. suis in pigs. This gene was also found to be expressed in human patients during the China outbreaks. 

The knowledge of these genes has helped scientists to develop a faster and better diagnosis tool to identify human-associated strains of S. suis. 

The discovery and understanding of HAC and HAC-specific genes and their evolutionary traits have helped scientists in developing various markers for diagnosis. Furthermore, the different membrane proteins acting as antigens are especially significant since they may be considered as potential candidates for vaccine development in the future.

Also read:Population-scale long-read sequencing and its approaches

Sources:

Dong, X., Chao, Y., Zhou, Y., Zhou, R., Zhang, W., Fischetti, V. A., Wang, X., Feng, Y., & Li, J. (2021). The global emergence of a novel Streptococcus suis clade associated with human infections. EMBO molecular medicine, e13810. Advance online publication. https://doi.org/10.15252/emmm.202013810

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About Author– Hari Krishnan is a research enthusiast in Cell biology and Cell signalling. He is currently a final year Biotechnology Engineering student. He is a prolific Scientific writer with vast knowledge in diverse backgrounds of biotechnology. He is constantly focused on improving his knowledge and laboratory skills through various internships. A Chennai native, Hari is a spicy food lover and passionate about music and sports.

Publications-

  1. Krishnan, H. (2021). COMPARISON OF THE DRUG ENTRAPMENT EFFICIENCY OF ALMOND GUM (Badam Pisin) TO SPAN-60 NIOSOMES BY FOLIN- CIOCALTEU ASSAY. BioRxiv. https://doi.org/10.1101/2021.04.03.438312 
  2. Krishnan, H. (2020). TELOMERASE TARGETING IN CANCER. International Research Journal of Modernization in Engineering Technology and Science. https://doi.org/10.3390/cancers12082260   
  3. Hari Krishnan, R. (2021, June 20). Addressing continued COVID-19 transmission despite universal masking. BioXone. https://bioxone.in/news/worldnews/addressing-continued-covid-19-transmission-despite-universal-masking/ 

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