Holistic Characterization of a Typhimurium Infection Model Using Integrated Molecular Imaging.

A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Typhimurium infection in the liver of a mouse model using the Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism.

Paratyphi A Outer Membrane Vesicles Displaying Vi Polysaccharide as a Multivalent Vaccine against Enteric Fever.

Typhoid and paratyphoid fevers have a high incidence worldwide and coexist in many geographical areas, especially in low-middle-income countries (LMIC) in South and Southeast Asia. There is extensive consensus on the urgent need for better and affordable vaccines against systemic infections. Generalized modules for membrane antigens (GMMA), outer membrane exosomes shed by bacteria genetically manipulated to increase blebbing, resemble the bacterial surface where protective antigens are displayed in their native environment.

Within-host spatiotemporal dynamic of systemic salmonellosis: Ways to track infection, reaction to vaccination and antimicrobial treatment.

During the last two decades our understanding of the complex in vivo host-pathogen interactions has increased due to technical improvements and new research tools. The rapid advancement of molecular biology, flow cytometry and microscopy techniques, combined with mathematical modelling, have empowered in-depth studies of systemic bacterial infections across scales from single molecules, to cells, to organs and systems to reach the whole organism level. By tracking subpopulations of bacteria in vivo using molecular or fluorescent tags, it has been possible to reconstruct the spread of infection within and between organs, allowing unprecedented quantification of the effects of antimicrobial treatment and vaccination.

Dual role of splenic mononuclear and polymorphonuclear cells in the outcome of ciprofloxacin treatment of Salmonella enterica infections.

Objectives: To determine the immune cell populations associated with Salmonella enterica serovar Typhimurium before and after ciprofloxacin treatment using a murine model of systemic infection. The effect of depletion of immune cells associating with Salmonella on treatment outcome was also determined.

Methods: We infected mice with a Salmonella enterica serovar Typhimurium strain expressing GFP and used multicolour flow cytometry to identify splenic immune cell populations associating with GFP-positive Salmonella before and after treatment with ciprofloxacin.

Utilisation of the Prestwick Chemical Library to identify drugs that inhibit the growth of mycobacteria.

Tuberculosis (TB) is an infectious bacterial disease that kills approximately 1.3 million people every year. Despite global efforts to reduce both the incidence and mortality associated with TB, the emergence of drug resistant strains has slowed any progress made towards combating the spread of this deadly disease.