Trends in Microbiology
ReviewThe Role of the Host in Driving Phenotypic Heterogeneity in Salmonella
Section snippets
Complexity across the Infection Landscape
During infection, the host environment diversifies into areas with varying degrees of inflammation. The detection of invading pathogens recruits several immune cells to multiple host tissues, which orchestrate the appropriate defense response through antigenic detection, modulation of gene expression, and establishment of immunological memory 1, 2. Traditionally, these processes have been quantified at the population level, contributing to an oversimplified view of the infection process and the
Modeling Infection Heterogeneity with Salmonella
Depending on host immune status and the infecting strain, exposure to different Salmonella serotypes can lead to either self-limiting gastroenteritis or systemic typhoid-like infection, which can both be investigated with several well established animal models [10]. Most of what we know of Salmonella pathogenicity has been gleaned from laboratory strains of the nontyphoidal Typhimurium serovar – LT2, SL1344, and ATCC14028s [11] – which produce lethal infections and significant pathology in the
Invasion and Inflammation of the Intestinal Tract
The initial invasion of the intestinal epithelium is central to Salmonella pathogenesis. After oral infection of streptomycin pretreated mice, bacterial colonization is first localized to the terminal ileum, cecum, and colon, inducing pathology and inflammation in these areas [20]. The process of intestinal invasion and colonization has been considered highly T3SS-1-dependent, as SPI-1 mutants are significantly attenuated for cultured epithelial cell invasion and the induction of intestinal
Survival and Replication in the Intracellular Environment
Irrespective of the mechanisms underlying epithelium traversal and extraintestinal exit, the next stage of Salmonella pathogenesis is dependent upon intracellular adaptation, with Salmonella populations mostly occupying dendritic cells, macrophages, neutrophils, and fibroblasts [61]. Once infected, these host cells attempt to restrict the growth of internalized Salmonella with several antimicrobial activities. Here we highlight only a few of the diverse outcomes of Salmonella–macrophage
Growth and Spread of Salmonella at Systemic Sites
During the first day after infection, the total Salmonella burden within infected hosts is thought to initially decrease, due to a net balance of host-mediated killing over bacterial replication 94, 95. However, as infection proceeds, bacterial survival is favored by the transcriptional reprogramming that occurs in intracellular Salmonella to express genes that confer resistance to the natural antimicrobial mechanisms of the host innate immune system. This includes the expression of enzymes
Concluding Remarks
The asynchronous nature of bacterial infection within hosts creates a pool of phenotypic diversity that permits the exploitation of a wide range of niches, as well as the evasion of environmental and immunological stresses. Consistent with this, distinct subpopulations of both immune and bacterial cells emerge in the complex landscape of infection, creating microenvironments with different host–pathogen interaction outcomes. Despite being one of the most well-studied pathogenic organisms, the
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