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

Primrose Freestone,Hasan Yesilkaya,Sara Sandrini,Fayez Alghofaili

doi:10.1186/1471-2180-14-180

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.

Highlights

Host signals are being shown to have a major impact on the bacterial phenotype
Norepinephrine stimulates S. pneumoniae growth and biofilm formation Wildtype S. pneumoniae strain D39, routinely propagated in vitro or its mouse passaged stock, and the TIGR4 strain were inoculated into serum-medium (50% Sicard [26] and 50% serum-SAPI, a host-like serumsupplemented minimal medium); serum was included to simulate in vivo conditions [2,8,23]
A time course of growth in serum-medium in the presence and absence of the catecholamine is shown in Figure 1, which reveals that the cultures grew significantly better (P < 0.01) when NE was present, indicating that all of the pneumococcal strains were stress hormone responsive

Summary

Introduction

Host 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 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 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 serumtransferrin and inotrope uptake, as well as enhancing expression of key genes in central metabolism and virulence. The recognition that stress hormone release leads to increased risk of infection has come from the finding that stress –associated chemicals negatively modulate immune function [3], and to their impact on the growth and virulence of bacteria [2] Catecholamines have been shown to augment the growth of species including. Catecholamine inotropes used in the treatment of acutely ill patients (such as dopamine and epinephrine) have been shown to increase staphylococcal and pseudomonad biofilm formation and promote recovery from antibiotic damage [2,8,9]

Methods

Results

Discussion

Conclusion