Medecine

The non-competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (≥5 mg/kg), MK801 (≥0.1 mg/kg), and ketamine (>20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0–20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury. © 1992 Wiley-Liss, Inc.

Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are major respiratory
pathogens and can concurrently colonize the airways of patients with chronic obstructive
diseases, such as cystic fibrosis (CF). Airway epithelial cell signalling is critical to the activa-
tion of innate immune responses. In the setting of polymicrobial colonization or infection
of the respiratory tract, how epithelial cells integrate different bacterial stimuli remains
unknown. Our study examined the inflammatory responses to PA and SA co-stimulations.
Immortalised airway epithelial cells (Beas-2B) exposed to bacteria-free filtrates from PA
(PAF) induced a robust production of the neutrophil chemoattractant IL-8 while bacteria-
free filtrates from SA (SAF) had a minimal effect. Surprisingly, co-stimulation with PAF+SAF
demonstrated that SAF strongly inhibited the PAF-driven IL-8 production, showing that SAF
has potent anti-inflammatory effects. Similarly SAF decreased IL-8 production induced by
the TLR1/TLR2 ligand Pam 3 CysSK 4 but not the TLR4 ligand LPS nor TLR5 ligand flagellin
in Beas-2B cells. Moreover, SAF greatly dampened TLR1/TLR2-mediated activation of the
NF- κ B pathway, but not the p38 MAPK pathway. We observed this SAF-dependent anti-
inflammatory activity in several SA clinical strains, as well as in the CF epithelial cell line
CFBE41o-. These findings show a novel direct anti-inflammatory effect of SA on airway epi-
thelial cells, highlighting its potential to modulate inflammatory responses in the setting of
polymicrobial infections.

Salmonella Enteritidis is a non-typhoidal serovar of great public health significance worldwide. The RpoE sigma factor and CpxRA two-component system are the major regulators of the extracytoplasmic stress response. In this study, we found that the CpxR has highly significant, but opposite effects on the auto-aggregation and swarming motility of S. Enteritidis. Auto-aggregation was negatively affected in the ∆cpxR mutant, whereas the same mutant significantly out-performed its wild-type counterpart with respect to swarming motility, indicating that the CpxR plays a role in biofilm-associated phenotypes. Indeed, biofilm-related assays showed that the CpxR is of critical importance in biofilm development under both static (microtiter plate) and dynamic (flow cell) media flow conditions. In contrast, the RpoE sigma factor showed no significant role in biofilm development under dynamic conditions. Transcriptomic analysis revealed that the cpxR mutation negatively affected the constitutive expression of the operons critical for biosynthesis of O-antigen and adherence, but positively affected the expression of virulence genes critical for Salmonella-mediated endocytosis. Conversely, CpxR induced the expression of curli csgAB and fimbrial stdAC operons only during biofilm development and flagellar motAB and fliL operons exclusively during the planktonic phase, indicating a responsive biofilm-associated loop of the CpxR regulator.

n open environments such as water, enterohemorrhagic Escherichia coli O157:H7 responds to inorganic phosphate (Pi) starvation by inducing the Pho regulon controlled by PhoB. This activates the phosphate-specific transport (Pst) system that contains a high-affinity Pi transporter. In the Δpst mutant, PhoB is constitutively activated and regulates the expression of genes in the Pho regulon. Here, we show that Pi starvation and deletion of the pst system enhance E. coli O157:H7 biofilm formation. Among differentially expressed genes of EDL933 grown under Pi starvation conditions and in the Δpst mutant, we have found that a member of the PhoB regulon, waaH, predicted to encode a glycosyltransferase, was highly expressed. Interestingly, WaaH contributed to biofilm formation of E. coli O157:H7 during both Pi starvation and in the Δpst mutant. In the Δpst mutant, the presence of waaH was associated with lipopolysaccharide (LPS) R3 core type modifications, whereas in E. coli O157:H7, waaH overexpression had no effect on LPS structure during Pi starvation. Therefore, waaH participates in E. coli O157:H7 biofilm formation during Pi starvation, but its biochemical role remains to be clarified. This study highlights the importance of the Pi starvation stress response to biofilm formation, which may contribute to the persistence of E. coli O157:H7 in the environment.