6-hydroxydopamine-mediated release of norepinephrine increases faecal excretion ofSalmonella entericaserovar Typhimurium in pigs

Abstract

Salmonella enterica serovar Typhimurium is an animal and zoonotic pathogen of worldwide importance. In pigs, transport and social stress are associated with reactivation and spread of Salmonella Typhimurium infection. The stress-related catecholamine norepinephrine (NE) has been reported to activate growth and virulence factor expression in Salmonella; however the extent to which NE contributes to stress-associated salmonellosis is unclear. We studied the impact of releasing NE from endogenous stores during Salmonella Typhimurium infection of pigs by administration of 6-hydroxydopamine (6-OHDA), which selectively destroys noradrenergic nerve terminals. Treatment of pigs with 6-OHDA 7 or 16 days post-oral inoculation with Salmonella Typhimurium produced elevated plasma NE levels and transiently, but significantly, increased faecal excretion of the challenge strain. Oral administration of NE to Salmonella Typhimurium-infected pigs also transiently and significantly increased shedding; however pre-culture of the bacteria with NE did not alter the outcome of infection. Salmonella has been proposed to sense and respond to NE via a homologue of the adrenergic sensor kinase QseC. A ΔqseC mutant of Salmonella Typhimurium was consistently excreted in lower numbers than the parent strain post-oral inoculation of pigs, though not significantly so. 6-OHDA treatment of pigs infected with the ΔqseC mutant also increased faecal excretion of the mutant strain, albeit to a lesser extent than observed upon 6-OHDA treatment of pigs infected with the parent strain. Our data support the notion that stress-related catecholamines modulate the interaction of enteric bacterial pathogens with their hosts.

Effects of long-term construction noise on health of adult female Wistar rats

“…Stress causes hypothalamic-pituitary-adrenal (HPA) axis activation and gut microbiota dysbiosis (Galley and Bailey, 2014). The activation of the HPA axis produces changes in certain populations of bacteria (Pullinger et al 2010).…”

Microbial Endocrinology

“…Within two weeks, the time required typically for regeneration of the affected neurons, bacterial counts in the gut had returned to normal. More recently, a related study by Pullinger et al [50] that 6-OHDA treatment of pigs following post-oral inoculation with Salmonella Typhimurium produced elevated plasma noradrenaline levels and transiently but significantly, increased faecal excretion of the bacteria. Oral administration of noradrenaline to Salmonella-infected pigs also increased shedding of the Salmonella, although in contrast to the Toscano study [43], pre-treatment of the bacteria with noradrenaline had no significant effect on the outcome of the infection.…”

“…The abundance of noradrenaline-and dopaminecontaining nerve terminals within the enteric nervous system [8] suggests a microbe inhabiting the intestinal tract is likely to come into contact with catecholamines. Stress in animals, such as being chased by a predator, will increase systemic catecholamine levels as part of the 'fight and flight' response [2,8]; work from Bailey et al [47], Lyte and Bailey [49] and Pullinger et al [50] has showed that host stress directly affects the gut microflora. Perhaps this is because enteric microbes have evolved mechanisms to sense changes in fitness of their host by monitoring its stress hormone levels?…”

Stress at the intestinal surface: catecholamines and mucosa–bacteria interactions

“…The first, which utilized the systemic-wide release of catecholamines following the destruction of noradrenergic terminals by the selective neurotoxin 6-hydroxydopamine, demonstrated an increase in either indigenous Gram-negative bacteria, almost exclusively E. coli (Lyte and Bailey 1997), or in the amount of excreted S. enterica serovar Typhimurium following oral administration (Pullinger et al 2010b). In the second system, dopamine β-hydroxylase knockout mice, which are deficient in the production of NE and epinephrine, manifest differing susceptibility to infection with S. enterica serovar Typhimurium as compared to wild-type mice (Moreira et al 2010).…”