Salmonella
Research Article | Host-Microbe BiologyAn Advanced Human Intestinal Coculture Model Reveals Compartmentalized Host and Pathogen Strategies during Salmonella InfectionInfection research routinely employs in vitro cell cultures or in vivo mouse models as surrogates of human hosts. Differences between murine and human immunity and the low level of complexity of traditional cell cultures, however, highlight the demand for alternative models that combine the in vivo-like properties of the human system with straightforward experimental perturbation. Here, we introduce a 3D...
Research Article | Host-Microbe BiologyA Genome-Wide Knockout Screen in Human Macrophages Identified Host Factors Modulating Salmonella InfectionSalmonella exploits macrophages to gain access to the lymphatic system and bloodstream to lead to local and potentially systemic infections. With an increasing number of antibiotic-resistant isolates identified in humans, Salmonella infections have become major threats to public health. Therefore, there is an urgent need to identify alternative approaches to anti-infective therapy, including host-directed therapies. In...
Editor's Pick Research Article | Host-Microbe BiologyEstablishment of Chronic Typhoid Infection in a Mouse Carriage Model Involves a Type 2 Immune Shift and T and B Cell Recruitment to the GallbladderThe existence of chronic typhoid carriers has been in the public eye for over 100 years in part because of the publicity around Typhoid Mary. Additionally, it has been known for decades that the gallbladder is the main site of persistence and recently that gallstones play a key role. Despite this, very little is known about the physiological conditions that allow Salmonella...
Research Article | Ecological and Evolutionary ScienceSystems Biology and Pangenome of Salmonella O-AntigensLipopolysaccharides are a major component of the outer membrane in Gram-negative bacteria. They are composed of a conserved lipid structure that is embedded in the outer leaflet of the outer membrane and a polysaccharide known as the O-antigen. O-antigens are highly variable in structure across strains of a species and are crucial to a bacterium’s interactions with its environment. They constitute the first line of defense against both...
Editor's Pick Research Article | Host-Microbe BiologyTopological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during InfectionThe type 3 secretion system (T3SS) is a nanomachine required for virulence of many bacterial pathogens that infect humans. The system delivers bacterial virulence proteins into the cytosol of human cells, where the virulence proteins promote bacterial infection. The T3SS forms a translocon pore in the membranes of target cells. This pore is the portal through which bacterial virulence proteins are delivered by the T3SS into the...
Research Article | Host-Microbe BiologyBarcoded Consortium Infections Resolve Cell Type-Dependent Salmonella enterica Serovar Typhimurium Entry MechanismsSalmonella enterica serovar Typhimurium (S.Tm) is a widespread and broad-host-spectrum enteropathogen with the capacity to invade diverse cell types. Still, the molecular basis for the host cell invasion process has largely been inferred from studies of a few selected cell lines. Our work resolves the mechanisms that Salmonellae employ to invade...
Research Article | Molecular Biology and PhysiologyProgrammed Delay of a Virulence Circuit Promotes Salmonella PathogenicityTo accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogen Salmonella controls the timing and level of virulence gene expression by using an inhibitory protein, EIIANtr. A DNA binding master...
Research Article | Ecological and Evolutionary ScienceSalmonella enterica Phylogeny Based on Whole-Genome Sequencing Reveals Two New Clades and Novel Patterns of Horizontally Acquired Genetic ElementsRapid improvements in nucleotide sequencing access and affordability have led to a drastic increase in availability of genetic information. This information will improve the accuracy of molecular descriptions, including serovars, within S. enterica. Although the concept of serovars continues to be useful, it may have more significant limitations than previously...
Research Article | Host-Microbe BiologyGut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicansThe gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7–15, 2011, https://doi.org/10.3201/eid1701....
- Research Article | Host-Microbe BiologySsaV Interacts with SsaL to Control the Translocon-to-Effector Switch in the Salmonella SPI-2 Type Three Secretion System
Salmonella Typhimurium is an intracellular pathogen that uses the SPI-2 type III secretion system to deliver virulence proteins across the vacuole membrane surrounding intracellular bacteria. This involves a tightly regulated hierarchy of protein secretion controlled by two molecular switches. We found that SPI-2-encoded proteins SsaP and SsaU are involved in the first but not the second secretion switch. We identify key amino...