Lecture 10: Virulence factors - Adaptation in metabolism Flashcards
On what is the expression of metabolic pathways dependent?
The expression of certain metabolisms is dependent on the location/host and which nutrients are available. There is always a trade-of1f between cost (ATP) and benefit.
What metabolic interactions does a pathogen have with the host?
It senses the metabolic environment of the host, adapts to changing nutrient availability and competes with the host for metabolites.
What is an example that virulence factors are only expressed at the right location?
Enterohaemorrhagic Escherichia coli (EHEC) alters the expression of virulence genes in response to microbiota-derived sugars. On ingestion, microbiota-derived sugars, such as fucose, are sensed directly by EHEC through FusK which activates FusR, this activation acts as a signal that the bacterium is located in the host intestinal environment. The activation of FusKR leads to the alteration of virulence gene expression, which promotes the colonization of the intestine and subsequent disease progression. By using microbiota-derived signals to alter gene expression, EHEC can ensure that the virulence genes are only expressed in the correct environment.
How does Streptococcus pyogenes check if its at the right location?
S.pyogenes produces Streptolysin which will cause ER stress in the cell and the cell will excrete Asparagine which is the signal for the S. pyrogenes that it’s in the correct location and will alter its virulence gene expression. (but the host will know you are there)
What is quiescence?
non-growing but metabolically active state of pathogens.
How does Chlamydia trachomatis survive without Tryptophan?
Tryptophan levels are a cue for Chlamydia trachomatis quiescence responses. On infecting a host, C. trachomatis replicates in an intracellular compartment of epithelial cells. This leads to the activation of host immunity in which the production of high levels of IFNγ help to restrict and clear the infection. The production of IFNγ leads to the upregulation of indoleamine-2,3-dioxegenase (IDO), which, in turn, depletes host cells of their intracellular tryptophan pools. Replicating C. trachomatis senses the depletion of tryptophan and transitions into a non-replicating persistent form. Because C. trachomatis encodes a partial tryptophan operon it is able to survive in the absence of tryptophan by using indole from the microbiota. Following the resolution of the host immune response, IFNγ levels decrease and the concentration of intracellular tryptophan increases leading to the reactivation of C. trachomatis into a replicating form. By sensing the levels of tryptophan, C. trachomatis can persist in the host even in the face of active immunity by oscillating between replicating and non-replicating forms.
How does E.coli adapt to nutrient availability?
E.coli lac genes will only be expressed when there is lactose present, otherwise it will be blocked by a repressor protein. When there is lactose but low glucose there will be high expression, high glucose and lactose will be basal expression of lac genes.
How does Mycobacterium tuberculosis adapt to nutrient availability?
Carbon utilization by Mycobacterium tuberculosis is altered during active immune responses. On infection of resting macrophages, M. tuberculosis simultaneously uses a range of carbon sources to replicate, many of which are probably delivered by recycling endosomes in transferrin-receptor-positive vesicles. These carbon sources include fatty acids, cholesterol and carbohydrates, but none of these are individually required for growth under these conditions. On immune activation and the production of host IFNγ, the requirements for distinct carbon sources shift. The host transferrin receptor no longer localizes to the pathogen-containing vacuole, limiting the nutrients delivered from the extracellular fluid. This alteration in intracellular environment is mirrored by the increased dependence on genes that are required for the catabolism of a single carbon source — cholesterol. This suggests that host immune stress conditions alter the availability of, or preference for, specific macronutrients that are available for M. tuberculosis inside macrophages.
How does Staphylococcus aureus adapt to for immune evasion?
Staphylococcus aureus resists host nitric oxide responses through metabolic alterations. The production of host nitric oxide is a common strategy to restrict the replication of bacterial pathogens. S. aureus has evolved elegant mechanisms to resist nitric oxide toxicity and survive and replicate in the host. Following the production of nitric oxide during infection, the S. aureus two-component system SsrAB is activated and leads to the induction of the nitric oxide-inducible l-lactate dehydrogenase 1 (Ldh1). The upregulation of Ldh1 enables S. aureus to survive through lactate fermentation under both aerobic and anaerobic conditions, avoiding normal nitric oxide-mediated toxicity. Importantly, the activation of this metabolic pathway imposes a metabolic restriction on S. aureus, forcing the bacterium to utilize hexose through glycolysis. Therefore, by altering its core metabolic network, S. aureus is able to resist an otherwise efficient host immune mechanism.
How does Salmonella Typhimurium turn the immune response into an advantage?
Salmonella Typhimurium uses inflammation-mediated by-products to compete and survive in the intestinal environment. On ingestion S. Typhimurium competes relatively poorly with the host microbiota. However, S. Typhimurium actively induces inflammation in the intestinal environment, producing oxidized by-products of phagocyte activation including tetrathionate. Although these compounds are inert to the majority of the host microbiota, S. Typhimurium can use molecules, such as tetrathionate, as terminal electron acceptors and unique carbon sources, such as fructose–asparagine, enabling it to outcompete the resident microbiota by using anaerobic respiration. In this way S. Typhimurium uses the by-products of host inflammation in the intestines to overcome the competitive barriers imposed by the resident microflora.
How does S.typhimurium affect host lymphocytes?
Lymphocytes need asparagin for replication, and S. typhimurium produces L-asparaginase which cleaves asparagin.
How do pathogens affect arganine?
C. trachomatis inhibits NOS2 which will class switch macrophages to M2. S. aureus induces L-arganine to be conferted into L-ornithine so there will be more ammonia which influences the pH.
