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IIDR Trainee Discovers How Streptococcus Protects Itself from Competitor Bacteria

Master’s student Tim Klein of Dr. John Whitney’s lab is studying how the bacterial type VII secretion system of Gram-positive bacteria mediates interbacterial competition.

Bacteria often inhabit densely populated niches in which different species of microbes are competing with one another for available resources. One way in which Gram-positive bacteria compete with neighboring bacteria is by secreting antibacterial toxins through a multi-subunit protein complex known as the bacterial type VII secretion system (T7SS).

In previous work, IIDR scientist Dr. John Whitney identified the T7SS-exported antibacterial protein TelC as a crucial component of interbacterial competition. This protein is produced by the opportunistic pathogen Streptococcus intermedius, and exerts toxicity in the inner wall zone of Gram-positive bacteria. Intriguingly, it was also found that adjacent sister cells protect themselves against TelC through the expression of an immunity protein called TipC.

In the present study published in the Journal of Molecular Biology, IIDR MSc student Tim Klein of Dr. Whitney’s lab sought to understand the mechanism by which TipC protects cells from TelC-based toxicity.

First, using subcellular localization and protein X-ray crystallography experiments, the team determined that the region of TipC that inhibits TelC activity adopts a crescent-shape fold that exists in the inner wall zone of Gram-positive bacteria – the precise site of TelC activity.

Using structural and informatic approaches, the team also found that the concave surface of the crescent-shaped TipC protein is required for TipC’s direct interaction with TelC. Furthermore, with the help of collaborators at the Centre for Bacterial Cell Biology at Newcastle University, it was shown that this interaction is required for the ability of TipC to inhibit the toxic cell wall-disrupting activity of TelC.

This study represents the first in-depth characterization of a T7SS immunity protein and, consequently, will contribute to the fields of microbial competition and antimicrobial resistance.

Read the full publication in the Journal of Molecular Biology here.

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