No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

The food-borne pathogen Listeria monocytogenes is more salt tolerant in the complex medium brain heart infusion (BHI, 2.0M NaCI upper limit for growth) than in a chemically-defined medium (DM, 1.0M NaCI upper limit for growth). The components in BHI responsible for the characteristic salt tolerance of L. monocytogenes are peptone and glycine betaine. At high osmolarity, the growth stimulation by peptone was higher than expected from nutritional supplementation, indicating that an osmoprotective mechanism was also at play. Peptone provided a higher level of osmotic protection than the compatible solute glycine betaine which was a moderate osmoprotectant. Our growth data demonstrated that of the free amino acids and peptides contained in peptone it is the peptides which are the osmoprotectants for L monocytogenes. Furthermore, specific peptides, such as PGG (prolyl-glycyl- glycine) and PHP (prolyl-hydroxyproline), behaved in growth experiments as the compatible solute glycine betaine, i.e. stimulation of growth at high osmolarity and no effect at low osmolarity. Our analysis of the changes in the intracellular pools of amino acids, under conditions of sosmotic stress, when peptone or specific peptide are supplied to the growth medium, has shown the following features in the mechanism of adaptation of L. monocytogenes to osmotic stress: i) Peptides are taken up, by at least two specific transport systems. ii) Subsequently, peptides are hydrolysed intracellularly by peptidases. iii) As a consequence of ii), a significant increase in the pool of free amino acids occurs. Osmoadaptation in L. monocytogenes iv) We have also demonstrated that depending on the nature of the constituent amino acids, some peptides are not fully hydrolysed which leads to the accumulation of an intracellular peptide pool in L. monocytogenes. v) Proline, glycine and hydroxyproline are the amino acids preferentially accumulated as free amino acids or as part of peptides. vi) The intracellular accumulation of free amino acids and peptides is positively correlated to an increase in the external osmolarity and has an important role in the osmoadaptation of L. monocytogenes.

Neisseria meningitidis (Nm) disease occurs worldwide. Disease incidence rates can vary from 1 to 1000 cases per 100,000 with the highest incidence found in the sub-Saharan Africa meningitis belt. Nm has evolved a number of mechanisms to evade host immunity. This includes the production of genetic variants through re-combinatorial events, which is thought to have contributed to the evolution of hyper-invasive lineages that are largely responsible for meningococcal disease. Antigenic diversity of Nm surface proteins has been the main limitation in the design of broadly protective vaccines, particularly against capsular serogroup B strains. To overcome this problem, several Nm genomes have been sequenced in an effort to find highly sequence-conserved surface antigens recognized by the human immune system in order to develop a vaccine, which would be broadly protective against disease. Nm genomes contain over 2 million base pairs that contain between 2000 and 2500 open reading frames. Add to this the difficulty of identifying highly conserved recombinant antigens with strong intrinsic immunostimulatory properties, makes vaccine design and development a daunting task. Recent advances in our understanding of the interactions between innate and acquired immunity, and the discovery of pattern recognition receptors, including Toll-like receptors (TLRs), have ushered in a new set of adjuvant compounds, TLR agonists, which invoke strong humoral and cellular responses with nominal toxicity and adverse reactions. These insights have opened up new areas of vaccine research to combat invasive Nm disease.

Many infectious pathogens, and in particular viruses, have an extremely high rate of mutation. This can lead to rapid evolution driven by selection pressures operating at both the within- and between-host levels, as strains compete for resources within their chosen host while also competing to effectively transmit to new hosts. In the case of chronic viral infections, such as the human immunodeficiency virus (HIV) or hepatitis C, substantial viral evolution may take place within a single infected host. The fitness of a pathogen has been studied at the between-host level and at the within-host level, but linking the two levels of selection pressure is a difficult problem that has yet to be studied satisfactorily. We modify a simple model describing the within host dynamics of HIV infection by including multiple pathogen strains with different properties and allowing these strains to mutate. Within the host we observe different strategies for pathogen success during different stages of infection, which often leads to different strains predominating within the host over the course of infection. We then embed our within-host model into a Monte Carlo simulation that models the interactions between infected individuals. This approach allows us to combine selective pressure at the within-host level with pressures at the between-host level and helps us to predict which strains are most likely to be present within the population. We show that under our model assumptions the co-existence of multiple strains is possible and we explore the factors leading to the success of a pathogen.