PAULA SALGADO

Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University  

Clostridium difficile pathogenicity: insights at atomic level

Host: Maria João Romão 

Abstract

Our multidisciplinary work focuses on key aspects of C. difficile virulence at the molecular level. Recent work on two key aspects will be presented.

One major interest is the proteinaceous surface layer - S-layer - that covers the whole bacterium cell. Despite being present in >80% of bacteria and proposed to be important for virulence of several pathogens, including C. difficile and Bacillus anthracis, S-layers are poorly studied and understood. We now have the first structure of a full S-layer protein - SlpA - and combining X-ray models, electron diffraction and microbiology studies can propose a model for S-layer assembly and organisation.

Another key focus in the lab is spore formation - the infective agents in C. difficile infections. A universal feature of endosporulation is the engulfment of the forespore by the larger mother cell at an intermediate stage in the process. We have previously identified a protein complex essential for engulfment and recent work has focussed assessing the suitability of targeting this complex as a potential therapeutic target. Recently, we investigated the role of the peptidoglycan degradation machinery in engulfment and sporulation. Understanding the molecular details of these machineries and their relation to pathogenicity are essential for the development of more targeted, novel therapeutic approaches to treating CDI.

Short Bio

Paula Salgado is a structural biologist with a keen interest in proteins associated to human disease, particularly those caused by infectious agents. After a Biochemistry degree at University of Porto, followed by a PhD at Oxford University and postdoc positions at Birkbeck/UCL and Imperial College, she recently moved to Newcastle University to establish her own Structural Microbiology research group. Work in the Salgado lab combines protein crystallography with microbiology to understand key aspects of C. difficile virulence at the molecular level. 
Of particular interest are the mechanisms that allow C. difficile to  form resistant dormant cells - spores - which have been identified as the transmission agent in C. diff infections (CDI). Surface proteins, particularly the para-crystalline S-layer that covers the bacterium and the motility-related Type IV pili that are related to mechanisms of colonisation are also a focus of the lab.