ABSTRACT
Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent post-translational control, specifically governing type III cytotoxin secretion, exists in this species.
Subject(s)
Gene Expression Regulation, Bacterial , Leukocidins/metabolism , Pseudomonas aeruginosa/pathogenicity , Quinolones/metabolism , Quorum Sensing , Humans , Leukocidins/biosynthesis , Oligopeptides/biosynthesis , Pancreatic Elastase/biosynthesis , Pneumonia, Ventilator-Associated/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , Virulence Factors/biosynthesisSubject(s)
Depression/drug therapy , Thyroid Hormones/therapeutic use , Drug Therapy, Combination , Electroconvulsive Therapy , Humans , Imipramine/therapeutic use , Injections, Intravenous , Thyrotropin/administration & dosage , Thyrotropin-Releasing Hormone/administration & dosage , Triiodothyronine/therapeutic useSubject(s)
Glucagon , Peptides , Adult , Amino Acid Sequence , Antigen-Antibody Complex , Binding Sites , Humans , Immunochemistry , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Lipid Mobilization , Middle Aged , Stimulation, Chemical , Structure-Activity RelationshipABSTRACT
gamma-Hydroxybutyrate and ethanol, as well as gamma-butyrolactone and ethanol are potentiative with respect to duration of loss of the righting reflex (sleep time). The concentration of ethanol in the liver decreases from 30 to 90 minutes after rats are injected with ethanol, but there is no change when ethanol is injected with gamma-butyrolactone. In view of the fact that gamma-hydroxybutyrate is a natural intermediate in brain, the effects of ethanol on the central nervous system may be mediated through its interaction with gamma-butyrolactone.
