Sympathetic neurotransmitters render pathogens vulnerable to cathelicidin, impairs biofilm formation
Kofi
hand-in-hand with the loss of sympathetics in Crohn's and the chronic
bacterial overgrowth. It also indicates that these "pathogenic"
bacteria may not really be pathogens at all and that they're only
getting out of control when local sympathetic nerves short out.
In the case of sinusitis, it makes me think there's an underlying defect
in sympathetic innervation leading to biofilm accumulation.
J Bacteriol. 2009 Nov 20
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Genome-wide Transposon Mutagenesis Identifies a Role for Host
Neuroendocrine Stress Hormones in Regulating the Expression of Virulence
Genes in Salmonella.
Spencer H, Karavolos MH, Bulmer DM, Aldridge P, Chhabra SR, Winzer K,
Williams P, Khan CM.
Institute for Cell and Molecular Biosciences, The Medical School,
Newcastle University, Newcastle NE2 4HH; School of Molecular Medical
Sciences, Centre for Biomolecular Sciences, University Park, University
of Nottingham, Nottingham NG7 2RD.
Bacterial sensing of environmental signals plays a key role in
regulating virulence and mediating bacterial -host interactions. The
sensing of the neuroendocrine stress hormones epinephrine (adrenaline)
and norepinephrine (noradrenaline) plays an important role in modulating
bacterial virulence. We used MudJ transposon mutagenesis to globally
screen for genes regulated by neuroendocrine stress hormones in
Salmonella enterica serovar Typhimurium. We identified eight hormone
regulated genes, including yhaK, iroC, nrdF, accC, yedP, STM3081 and the
virulence-related genes virK and mig14. The mammalian alpha-adrenergic
receptor antagonist phentolamine reversed the hormone mediated effects
on yhaK, virK and mig14, but did not affect the other genes. The
beta-adrenergic receptor antagonist propranolol had no activity in these
assays. The virK and mig14 genes are involved in antimicrobial peptide
resistance, and phenotypic screens revealed that exposure to
neuroendocrine hormones increased the sensitivity of S. Typhimurium to
the antimicrobial peptide LL-37. A virK mutant and a virK-mig14 double
mutant also displayed increased sensitivity to LL-37. In contrast to
Enterohaemorrhagic Escherichia coli (EHEC), we have found no role for
the two component systems QseBC and QseEF in the adrenergic regulation
of any of the identified genes. Furthermore, hormone-regulated gene
expression could not be blocked by the QseC inhibitor LED209, suggesting
that sensing of hormones is mediated through alternative signalling
pathways in S. Typhimurium. This study has identified a role for host
derived neuroendocrine stress hormones in down-regulating S. Typhimurium
virulence gene expression to the benefit of the host, thus providing
further insights into the field of host-pathogen communication.
PMID: 19933366