A Quorum Sensing Regulated Small Volatile Molecule Reduces Acute Virulence and Promotes Chronic Infection Phenotypes

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Family burden related to mental and physical disorders in the world:results from the WHO World Mental Health (WMH) surveys

<p>Objective: To assess prevalence and correlates of family caregiver burdens associated with mental and physical conditions worldwide.</p><p>Methods: Cross-sectional community surveys asked 43,732 adults residing in 19 countries of the WHO World Mental Health (WMH) Surveys about chronic physical and mental health conditions of first-degree relatives and associated objective (time, financial) and subjective (distress, embarrassment) burdens. Magnitudes and associations of burden are examined by kinship status and family health problem; population-level estimates are provided.</p><p>Results: Among the 18.9-40.3% of respondents in high, upper-middle, and low/lower-middle income countries with first-degree relatives having serious health problems, 39.0-39.6% reported burden. Among those, 22.9-31.1% devoted time, 10.6-18.8% had financial burden, 23.3-27.1% reported psychological distress, and 6.0-17.2% embarrassment. Mean caregiving hours/week was 12.9-16.5 (83.7-147.9 hours/week/100 people aged 18+). Mean financial burden was 15.1% of median family income in high, 32.2% in upper-middle, and 44.1% in low/lower-middle income countries. A higher burden was reported by women than men, and for care of parents, spouses, and children than siblings.</p><p>Conclusions: The uncompensated labor of family caregivers is associated with substantial objective and subjective burden worldwide. Given the growing public health importance of the family caregiving system, it is vital to develop effective interventions that support family caregivers.</p>

The hierarchy quorum sensing network in Pseudomonas aeruginosa

10.1007/s13238-014-0100-xProtein and Cell6126-4