Host stress hormone norepinephrine stimulates pneumococcal growth, biofilm formation and virulence gene expression

Abstract

BackgroundHost signals are being shown to have a major impact on the bacterial phenotype. One of them is the endogenously produced catecholamine stress hormones, which are also used therapeutically as inotropes. Recent work form our laboratories have found that stress hormones can markedly increase bacterial growth and virulence. This report reveals that Streptococcus pneumoniae, a commensal that can also be a major cause of community acquired and nosocomial pneumonia, is highly inotrope responsive. Therapeutic levels of the stress hormone norepinephrine increased pneumococcal growth via a mechanism involving provision of iron from serum-transferrin and inotrope uptake, as well as enhancing expression of key genes in central metabolism and virulence. Collectively, our data suggests that Streptococcus pneumoniae recognises host stress as an environmental cue to initiate growth and pathogenic processes.ResultsEffects of a clinically attainable concentration of norepinephrine on S. pneumoniae pathogenicity were explored using in vitro growth and virulence assays, and RT-PCR gene expression profiling of genes involved in metabolism and virulence.We found that norepinephrine was a potent stimulator of growth, via a mechanism involving norepinephrine-delivery of transferrin-iron and internalisation of the inotrope. Stress hormone exposure also markedly increased biofilm formation. Importantly, gene profiling showed that norepinephrine significantly enhanced expression of genes involved in central metabolism and host colonisation. Analysis of the response of the pneumococcal pspA and pspC mutants to the stress hormone showed them to have a central involvement in the catecholamine response mechanism.ConclusionsCollectively, our evidence suggests that the pneumococcus has mechanisms to recognise and process host stress hormones to augment its virulence properties. The ability to respond to host stress signals may be important for the pneumococcal transition from colonization to invasion mode, which is key to its capacity to cause life-threatening pneumonia, septicaemia and meningitis.

Gut microbiome, surgical complications and probiotics

“…It has been shown that catecholamines directly affect the growth and expression of virulence-related factors in some bacteria, such as Yersinia enterocolitica , Escherichia coli (E. coli) , Pseudomonas aeruginosa (P. aeruginosa), Salmonella typhii or Campylobacter jejuni [38,39]. Furthermore, there is evidence that the in-vitro growth of the respiratory pathogen Bordetella bronchiseptica ( B. bronchiseptica ) is greatly enhanced in the presence of norepinephrine and that this ability is, in part, mediated by the ability of norepinephrine to increase the acquisition of transferrin-bound iron by B. bronchiseptica [40].…”

“…Furthermore, there is evidence that the in-vitro growth of the respiratory pathogen Bordetella bronchiseptica ( B. bronchiseptica ) is greatly enhanced in the presence of norepinephrine and that this ability is, in part, mediated by the ability of norepinephrine to increase the acquisition of transferrin-bound iron by B. bronchiseptica [40]. In the same manner, norepinephrine was found to increase the proliferation of Streptococcus pneumoniae by assisting the delivery of iron from host iron-binding proteins, while at the same time enhancing the formation of biofilms and thus increasing antibiotic resistance [39]. …”

Catecholamine-Stimulated Growth of Aeromonas hydrophila Requires the TonB2 Energy Transduction System but Is Independent of the Amonabactin Siderophore

“…Furthermore, NE increased both the cellular cytotoxicity and enterotoxicity of Vibrio parahaemolyticus and up-regulated the transcription of type III secretion system-1 genes (Nakano et al, 2007). Dopamine (Dopa) and epinephrine (Epi) have been found to increase biofilm formation in Streptococcus pneumonia (Sandrini et al, 2014). These observations indicate that stress hormones can regulate the behavior of pathogens.…”

Pancreatic Amylase Is an Environmental Signal for Regulation of Biofilm Formation and Host Interaction in Campylobacter jejuni

“…(26), Listeria monocytogenes (49), and Vibrio cholerae (50). In the case of Streptococcus pneumoniae, a number of host factors affect biofilm formation and structure, including norepinephrine (51) and extracytoplasmic ATP (52). Our work shows for the first time that avian and mammalian pancreatic amylase can act as an interkingdom signaling molecule and enhance C. jejuni growth and biofilm formation.…”