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Structure of Bacteria’s Sugar Coat Could Help Vaccine Development

Medical illustration of bacteria.
Credit: Photo by CDC on Unsplash.
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Many disease-causing bacteria like Streptococcus pneumoniae (S. pneumoniae) are encased in a sugar layer called the capsular polysaccharide (CPS). This layer is often essential for infections.

In a ground-breaking discovery by scientists from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), features of the CPS that help the bacteria to colonise the human respiratory tract was identified. The research showed that the structures of the CPS capsule and its types of linkages and combinations matter greatly in allowing the bacteria to better attach and survive on the lining of the upper and lower human respiratory tracts.

The team, led by Assistant Professor Chris Lok-To Sham and graduate student, Jade Chun Ye-Yu, from the Infectious Diseases Translational Research Programme at NUS Medicine, constructed bacterial mutants displaying one of the 84 types of CPS found in S. pneumoniae. The mutants were then introduced to respiratory cells to investigate their abilities to bind to the respiratory tracts. Using a molecular barcode to distinguish the strains, the team examined whether varying CPS in these mutants would affect binding on the nasal and bronchial cells.

The results showed that the CPS with rhamnose sugar residues bound poorly to the airway cells, while CPS with glycan motifs bound strongly. The experiment demonstrated that the structural configurations and the types of CPS play important roles in the strength of attachment and survival on the human airway.

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S. pneumoniae is a major driver of pneumonia, septicaemia, and meningitis. Collectively, these infections are among the leading causes of morbidity and mortality in the elderly and young children. To fight against these deadly infections, pneumococcal vaccines are administered to stimulate antibody production to the CPS. However, the bacteria can manipulate their CPS structure to evade these antibodies.

This biochemical warfare results in more than a hundred types of CPSs produced by S. pneumoniae, which increases the challenge of producing effective vaccines. While the diversity of CPS is well appreciated, what actually makes the CPS a lethal weapon for the bacteria remains unclear.

Reference: Chun YY, Tan KS, Yu L, et al. Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells. PNAS. 2023;120(13):e2213584120. doi: 10.1073/pnas.2213584120

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