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Richard Titball

Publications and source records attributed to Richard Titball.

4 recordsLinked to original sources
PubMed2005

A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C.

Clostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. Previously, a cellular UDP-Glc deficiency was related with a hypersensitivity to the cytotoxic effect of Cp-PLC. Because UDP-Glc is required in the synthesis of proteoglycans, N-linked glycoproteins, and glycosphingolipids, the role of these gly-coconjugates in the cellular sensitivity to Cp-PLC was studied. The cellular sensitivity to Cp-PLC was significantly enhanced by glycosphingolipid synthesis inhibitors, and a mutant cell line deficient in gangliosides was found to be hypersensitive to Cp-PLC. Gangliosides protected hypersensitive cells from the cytotoxic effect of Cp-PLC and prevented its membrane-disrupting effect on artificial membranes. Removal of sialic acids by C. perfringens sialidase increases the sensitivity of cultured cells to Cp-PLC and intramuscular co-injection of C. perfringens sialidase, and Cp-PLC in mice potentiates the myotoxic effect of the latter. This work demonstrated that a reduction in gangliosides renders cells more susceptible to the membrane damage caused by Cp-PLC and revealed a previously unrecognized synergism between Cp-PLC and C. perfringens sialidase, providing new insights toward understanding the pathogenesis of clostridial myonecrosis.

Animals↗
PubMed2005

Protective efficacy of a recombinant plague vaccine when co-administered with another sub-unit or live attenuated vaccine.

Vaccines against bioterrorism agents offer the prospect of providing high levels of protection against airborne pathogens. However, the diversity of the bioterrorism threat means that it may be necessary to use several vaccines simultaneously. In this study we have investigated whether there are changes to the protective immune response to a recombinant sub-unit plague vaccine when it is co-administered with other sub-unit or live attenuated vaccines. Our results indicate that the co-administration of these vaccines did not influence the protection afforded by the plague vaccine. However, the co-administration of the plague sub-unit vaccine with a live vaccine resulted in markedly increased levels of IgG2a subclass antibodies, and markedly reduced levels of IgG1 subclass antibodies, to the plague sub-unit vaccine. This finding might have implications when considering the co-administration of other vaccine combinations.

Animals↗
PubMed2004

The interaction of Pseudomonas aeruginosa PAK with human and animal respiratory tract cell lines.

A major virulence factor of a common human pathogen Pseudomonas aeruginosa, was investigated to determine if it dominated attachment interactions in a variety of in vitro cell culture systems. It was found that Type-IV pilus-type mechanisms, which mediated the attachment of P. aeruginosa to three human respiratory tract cell lines (A549, BEAS-2B and RPMI 2650) also mediated attachment to two respiratory tract cell lines from mouse (C57) and rat (L-2) to a similar degree. Significant differences were found in the number of P. aeruginosa associated with the human, rat and mouse cell lines. Additionally, differences were also found between A547, C57 and L-2 cells with respect to the moieties that P. aeruginosa interacted with at the level of the cell surface, suggesting that asialo-GM1 ligands were not the only structure that this bacterium could interact with in order to associate with host cells.

Animals↗