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Aoife Boyd (B.A (Mod), Ph.D.)

Lecturer

Pathogenic Mechanisms Group
Department of Microbiology
National University of Ireland, Galway
Galway
IRELAND

Aoife.Boydnuigalway.ie

The Pathogenic Mechanisms group

The Pathogenic Mechanisms group characterises the molecular mechanisms deployed by bacteria in order to colonise, survive and multiply during infection. By identifying and characterising the mechanisms that a bacterium uses to ensure its survival and persistence in a human or animal, these molecular activities can then be targeted for the development of antimicrobials and therapeutics.

The Pathogenic Mechanisms group utilises molecular techniques and facilities to investigate the relationships between bacteria and the cells of humans and animals. The balance of bacterial pathogenic mechanisms versus the host immune resistance mechanisms determines whether the bacteria will be killed and eliminated from the host or whether the bacteria will survive in the host and multiply. Bacteria have evolved a myriad of ways by which they can tip the balance in their favour.

Many bacteria use Type III Secretion Systems (TTSS) to modulate host cell behaviour. TTSS inject effector proteins inside eukaryotic cells, which then interact with human proteins and interfere with their normal activities. This leads to dysfunctional signalling within the eukaryotic cells, so that immune responses are perturbed and the host is no longer able to respond to the bacterial invasion and to destroy the bacteria. For example, cytokine and chemokine production levels may be altered, rates of internalisation of bacteria inside the eukaryotic cells may be modified or bacterial killing mechanisms may be modulated.       

We are studying TTSS in two bacterial pathogens - Bordetella pertussis and Vibrio parahaemolyticus. B. pertussis causes whooping cough and V. parahaemolyticus causes diarrhoea after eating contaminated shellfish. Our goal is to determine the importance and role of TTSS in the pathogenicity of Vibrio and Bordetella species.

• Investigating the effect of TTSS on host cell behaviour and how this facilitates bacterial survival
• Identifying and characterising TTSS effector proteins and the eukaryotic proteins that they target in order to elucidate their mechanism of action

As well as increasing understanding of Vibrio and Bordetella pathogenesis, this research would promote a broader knowledge of TTSS and immunomodulation by pathogenic organisms. It could lead to the development of the effector toxins as tools for cell biology research. Furthermore it could lead to the identification of candidate targets as diagnostic markers and for preventive and therapeutic antimicrobial strategies, thereby improving food safety and human health.

Experimental approaches and expertise

Protein studies:

• Protein expression, purification and analysis in prokaryotic and eukaryotic systems
• Protein immunodetection (ELISA and Westerns)
• Protein function characterisation

Microbial genetics:

• Microbial cell culture
• DNA cloning
• PCR
• Bioinformatics
• Mutagenesis

Host-pathogen interactions:

• Eukaryotic cell culture
• Bacteria-host cell co-incubation studies
• Bacterial attachment and internalisation
• Cytokine and chemokine quantification
• Cytotoxicity assays
• Cell signalling analysis

TTSS

TTSS directly channel effector proteins from bacteria into eukaryotic cells, where they interact with eukaryotic cell signalling proteins and sabotage the normal processes of the cell, thereby enhancing the ability of the bacteria to colonise the host. TTSS are necessary for the virulence of significant pathogens such as Salmonella, Shigella, Escherichia coli and Yersinia, as well as for Vibrio and Bordetella species.

Bordetella

The human pathogen Bordetella pertussis , the causative agent of whooping cough, and the broad-host range Bordetella bronchiseptica both infect the respiratory system.

Vibrio

V. parahaemolyticus has a severe detrimental economic impact on aquaculture, as well as being detrimental to human health.

Personnel

Collaborators

Prof Alan Baird
School of Agriculture, Food Science & Veterinary Medicine, UCD, Dublin, Ireland
Research Interests: Gastrointestinal Epithelial Cell Function
 
Prof Kingston Mills
School of Biochemistry and Immunology, TCD, Dublin, Ireland
Research Interests: Immune Regulation

Dr Ed Lavelle
School of Biochemistry and Immunology, TCD, Dublin, Ireland
Research Interests: Immunomodulation by Mucosal Adjuvants

Sources of Funding

• IRCSET, SFI, NUI Millenium Fund, EU Marie Curie.

Recent Publications

Abram F, E Starr, K Karatzas, K Matlawska-Wasowska, A Boyd, M Wiedmann, K Boor, D Connally, C O’Byrne. 2008. Identification of components of the sigma B regulon in Listeria monocytogenes that contribute to acid and salt tolerance. Applied and Environmental Microbiology. 74:6848-6858.

Fennelly N, F Sisti, S Higgins, P Ross, H van der Heide, F Mooi, A Boyd, K Mills. 2008. Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses. Infection and Immunity 76:1257-66.

Boyd A, P Ross, H Conroy, N Mahon, E Lavelle and K Mills. 2005. Bordetella pertussis adenylate cyclase toxin modulates innate and adaptive immune responses: distinct roles for acylation and enzymatic activity in immunomodulation and cell death. Journal of Immunology 175:730-838.

Mills K and A Boyd. 2005. Evasion of Immune Responses by Bacteria. In Topley & Wilson's Microbiology and Microbial Infections, 10th Ed: Immunology volume, Editors SHE Kaufmann & MW Steward. Published  by Hodder Arnold.

Ross P, E Lavelle, K Mills and A Boyd. 2004. Adenylate cyclase toxin from Bordetella pertussis synergizes with lipopolysaccharide to promote innate interleukin-10 production and enhances the induction of Th2 and regulatory T cells. Infection and Immunity 72 :1568-1579.

Taschner S, A Meinke, A von Gabain and A Boyd. 2002. Selection of peptide entry motifs by bacterial surface display: application to a genomic library of Staphylococcus aureus. Biochemistry Journal 367:393.

Etz H, DB Minh, T Henics, A Dryla, B Winkler, C Triska, A Boyd, J Söllner, W Schmidt, U von Ahsen, M Buschle, S Gill, J Kolonay, H Khalak, C Fraser, A von Gabain, E Nagy and A Meinke. 2002. Identification of in vivo expressed vaccine candidate antigens from Staphylococcus aureus. PNAS 99: 6573-6578.

Boyd A and G Cornelis. 2001. Yersinia in Principles of Bacterial Pathogenesis, Academic Press, EA Groisman (ed.)

Boyd A, I Lambermont and G Cornelis. 2000. Competition between the Yops of Yersinia enterocolitica for delivery into eukaryotic cells: Role of the SycE chaperone binding domain of YopE. Journal of Bacteriology 182: 4811-4821.

Boyd A, N Grosdent, S Tötemeyer, C Geuijen, S Bleves, M Iriarte, I Lambermont, J-N Octave, and G Cornelis. 2000. Yersinia enterocolitica can deliver Yop proteins into a wide range of cell types: Development of a delivery system for heterologous proteins. European Journal of Cell Biology 79: 659-671.

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