Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae

Abstract

Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

Bacterial peptide transporters: Messengers of nutrition to virulence

“…This may slow down the growth but does not affect survival and therefore leave little scope for the development of resistance. Metabolism associated genes of pathogens have been consistently linked with virulence of major pathogens, [1][2][3][4][5][6][7][8][9] such as, role of carbon metabolism related pathways like glycolysis 10 and TCA cycle 11 in virulence of Salmonella Typhimurium and requirement of metabolism associated pathways for protection of Mycobacterium tuberculosis from host immune system. 9 Salmonella is even known to modulate host to exploit the limited supply of nutrients.…”

Temperature-responsive in vitro RNA structurome of Yersinia pseudotuberculosis

“…An intercistronic RNAT is present upstream of low calcium response gene F (lcrF) coding for the master regulator of Yersinia virulence (6). Temperature and nutrient changes experienced during the early stage of infection, when the bacterium enters a warmblooded host, are the major cues of a complex gene expression cascade inducing not only virulence factors but also a metabolic switch to adapt to the host environment (27). A recent transcriptome study revealed 324 differentially regulated Y. pseudotuberculosis genes when cells were grown at 25°C or 37°C (28).…”

RNA structures are involved in the thermoregulation of bacterial virulence-associated traits

“…These crucial virulence genes for virulence are regulated at the level of transcription by the LcrF (also called VirF) activator [23,27].…”

“…In many of these cases, this information is encoded in mobile genetic elements such as plasmids, phages, or pathogenicity islands (such as with Escherichia coli and Vibrio cholerae [13][14][15][16][17][18][19][20]). Some bacteria infect specific organs or tissues, while others have the ability to produce systemic infections [21][22][23][24][25][26]. It is therefore not feasible to make generalizations about the mechanisms involved in the genetic regulation of genes coding for virulence-associated traits in different bacterial pathogens.…”