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PhD studentship in Structural Microbiology – “C. difficile S-layer variation: from structure to role in disease” at Newcastle University on FindAPhD.com

PhD Project - PhD studentship in Structural Microbiology – “C. difficile S-layer variation: from structure to role in disease” at Newcastle University, listed on FindAPhD.com

MSCA opens €417 million call for Postdoctoral Fellowships

Postdoctoral Fellowships offer researchers holding a PhD the opportunity to gain new skills and experience while carrying out their own research project abroad. The deadline to apply is 11 September 2024.

An intact S-layer is advantageous to Clostridioides difficile within the host

Author summary The S-layer of C. difficile is a paracrystalline array that covers the outer surface of the bacterial cell but its contribution to overall disease remains unclear. As previously described, spontaneous slpA-null mutant, FM2.5, with a point mutation in slpA offered an opportunity to study the role of the S-layer in disease. Here, we confirm that this strain is less virulent in vivo despite effectively colonising the host and producing toxin. We also show in vivo selection for sequence modifications that restore slpA translation and produce an S-layer. While such modifications do not affect the overall 3D structure of individual SlpA (sub)domains, they can lead to altered orientation of the structural domains and subsequent S-layer assembly. Importantly, RNA-Seq analysis in vitro showed large differences in gene expression between FM2.5 and R20291. Detected differences in transcription of genes involved in toxin expression and sporulation suggests that the S-layer provides a selective survival advantage within the host, which contributes to disease severity.