Regulatory principles governing Salmonella and Yersinia virulence

Abstract

Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process.

Pathogenicity island excision during an infection by Salmonella enterica serovar Enteritidis is required for crossing the intestinal epithelial barrier in mice to cause systemic infection

“…Notably, the main mechanism used by Salmonella to adapt to environmental conditions during the initial passage through the host gut are encoded in the core genome, which acts independent of the genes acquired by HGT, including the virulence genes encoded in SPIs. These regulatory systems encoded within these SPIs comprise, among others, the activation of ATR systems [41][42][43], systems related to survival under limitation of nutrient step [44,45], tolerance to hyperosmolarity and anaerobic environments [46][47][48], as well as quorum sensing [49]. Although initially these systems are responsible for the adaptation to the adverse intestinal environment of the host, some of them (such as the two-component systems PhoPQ and PmrAB, or the OmpR protein) are also responsible for the activation of genes encoded within the pathogenicity islands and other HGT elements, to ensure the passage through the intestinal barrier [50][51][52].…”

Urease Expression in Pathogenic Yersinia enterocolitica Strains of Bio-Serotypes 2/O:9 and 1B/O:8 Is Differentially Regulated by the OmpR Regulator

“…It has been relatively well established that although Y. enterocolitica strains possess the same virulence factors, their expression profiles can differ significantly (Schmühl et al, 2019). This may be the consequence of the finding that even small alterations in the content and organization of the genetic information may alter the expression pattern of virulence genes and their regulators in response to environmental factors (Uliczka et al, 2011;Erhardt and Dersch, 2015).…”

“…Yersinia enterocolitica synthesizes numerous virulence factors that are active at different stages of an infection and whose expression is altered according to the diverse growth conditions experienced by these bacteria in mammalian hosts (Straley and Perry, 1995;Marceau, 2005;Erhardt and Dersch, 2015;Chen et al, 2016). It was previously demonstrated that a functional urease is essential for the survival of Y. enterocolitica O:9 during passage through the stomach (De Koning-Ward and Robins-Browne, 1995;Young et al, 1996), and is also necessary for full virulence in oral infections in the rat model (Gripenberg-Lerche et al, 2000).…”

High mannose-specific lectin Msl mediates key interactions of the vaginal Lactobacillus plantarum isolate CMPG5300

“…To our knowledge, plasmid-encoded adhesins have so far not often been reported in lactobacilli except for a study on the probiotic intestinal strain L. paracasei NFBC338 which encodes for a collagen-binding protein (CD00222) on one of its plasmids20. In contrast, plasmid-encoded adhesins and virulence factors that are well-characterized are found especially in enteropathogenic strains such as Yersinia and Salmonella 21. The plasmid location of the msl gene could suggest that it is a recently acquired property of L. plantarum CMPG5300 through horizontal gene transfer.…”