Salmonellae invasion and intracellular replication within host cells results in a range of diseases including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms by which Salmonellae alter host cell physiology through the delivery of effector proteins with specific activities, and through the modulation of defence and stress response pathways in the host. In this Review, we summarize our current knowledge of the complex interplay of bacterial and host factors that lead to inflammation, disease and in most cases, control of Salmonellae infection, particularly Salmonella enterica serovar Typhimurium, by its animal hosts. We also highlight gaps in our knowledge of the contributions of Salmonellae and the host to disease pathogenesis and suggest future avenues for further study.

No abstract

Rho-family GTPases are essential eukaryotic signaling molecules that regulate cellular physiology. Virulence factors from various pathogens alter GTPase signaling by functioning as GTPase activating factors (GAPs), guanine exchange factors (GEFs) or direct covalent modifiers. Bacterial virulence factors that sense rather than alter Rho-family GTPase signaling states have not been previously described. Here, we report that the translocated Salmonellae virulence factor SseJ binds to the GTP bound form of RhoA with resultant stimulation of its enzymatic activity that results in host cell membrane cholesterol esterification. Therefore, GTPase mediated downstream activation is not exclusive to eukaryotic proteins, and a bacterial protein has evolved to recognize the GTPase signaling state of RhoA to regulate its enzymatic activity as part of the host-pathogen interaction.

No abstract

Pseudomonas aeruginosa is an important opportunistic pathogen that has become a serious problem due to increased rates of antibiotic resistance. Due to this along with a dearth in novel antibiotic development, especially against Gram-negative pathogens, new therapeutic strategies are needed to prevent a post-antibiotic era. Here we describe the importance of the vacJ/Mla pathway in resisting bactericidal actions of the host innate immune response. P. aeruginosa tn5 transposon mutants in genes from the VacJ/Mla pathway showed increased susceptibility to killing by the host cathelicidin antimicrobial peptide, LL-37 when compared to the wild-type parent strain. The P. aeruginosa vacJ− mutant demonstrated increased membrane permeability upon damage as well as sensitivity to killing in the presence of the detergent sodium dodecyl sulfate and the divalent cation chelator EDTA. When exposed to human whole blood and serum complement, the vacJ− mutant was killed more rapidly when compared to the wild-type parent strain and complemented mutant. Finally, in an in vivo mouse lung infection model, infection with the vacJ− mutant resulted in reduced mortality, lower bacterial burden, and reduced lung damage when compared to the wild-type strain. This study highlights the potential in therapeutically targeting the VacJ/Mla pathway in sensitizing P. aeruginosa to killing by the host innate immune response.