Light Modulates Important Pathogenic Determinants and Virulence in ESKAPE Pathogens Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus.

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa (ESKAPE) priority pathogens, which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens, light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility, and growth under iron-deprived conditions are modulated by light in S. aureus Light also regulates persistence, metabolism, and the ability to kill competitors in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, although the response is not the same in the different species; virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) is involved in virulence modulation by light in A. baumannii Overall, this fundamental knowledge highlights the potential use of light to control pathogen virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration.IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease; in the presence of light, some of them become more aggressive, while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to the control of infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

The Quinpirole Hypolocomotive Effects are Strain and Route of Administration Dependent in SHR and SLA16 Isogenic Rats.

The SHR and SLA16 inbred strains present behavioral differences in anxiety/emotionality that could be under the influence of dopaminergic neurotransmission. In order to investigate the role of D2 receptors in modulating such differences, an agonist (quinpirole) and an antagonist (haloperidol) of this receptor were administered, either via systemic injection (IP), or microinjected into the ventral area of the hippocampus (vHIP). Quinpirole and haloperidol IP decreased locomotor activity, only in SLA16 rats in the open-field (OF), and in both strains in the elevated plus-maze (EPM). Quinpirole also increased the preference for the aversive areas of the EPM. Quinpirole vHIP decreased locomotor activity in both strains. Haloperidol vHIP did not elicit behavioural changes and no differences in the levels of D2 receptors and of dopamine transporter in the hippocampus were found. Results indicate that systemic activation/blocking of D2 receptors caused a strain-dependent hypolocomotion, whereas activation of D2 receptors in the vHIP, but not D2 receptor antagonism, regardless of dose, decreased general locomotor activity in the two strains. Therefore, we suggest that genomic differences in the chromosome 4 can influence the locomotor activity regulated by the D2 dopaminergic receptor, especially in the vHIP.

Morphological and functional features of the sex steroid-responsive posterodorsal medial amygdala of adult rats.

The rat posterodorsal medial amygdala (MePD) expresses receptors for gonadal hormones and integrates sex steroid-sensitive subcortical networks. Male-female differences are found in the morphology, connectivity, and local neuropil structure of MePD. For example, dendritic spine density is sexually-dimorphic and changes with the estrous cycle and following gonadal hormones manipulations. Due to its connectivity, the MePD may affect emotionally-loaded social behaviors, according to a former Newman's seminal proposition. Unilateral fiber-sparing ibotenic acid damage of the MePD does not impair male sexual behavior. However, microinjecting glutamate and histamine into the right MePD facilitates ejaculation. Further, MePD-lesioned rats are not different from normal rats in anxiety-like behavior as evaluated by the elevated plus maze test or innate fear test induced by a live cat. In another study, an adapted model for inducing aggressive behavior in rats by a brief period of restraint prior to the resident-intruder paradigm was used to study Fos-immunoreactivity in the MePD. Following stressful stimulation (restraint) or the restraint and fight condition, but not after aggression alone, Fos-immunoreactivity was detected in the MePD. Microinjecting the inhibitory neuropeptide somatostatin into the right MePD notably reduces fighting behavior without affecting locomotion. Overall, these data indicate that sex steroids and local neurochemical stimulatory/inhibitory transmitters modulate the MePD and reinforce the idea that this area is a node for modulating social behavior neural networks.

[Usefulness of temporal bicameral stimulation in the interruption of refractory ventricular tachycardia]. / Utilità della stimolazione bicamerale temporanea nella interruzione delle tachicardie ventricolari refrattarie.

The occurrence of sustained ventricular tachycardia with worsening hemodynamic performance in patients with ischemic heart disease can represent a critical event when the arrhythmia, refractory to antiarrhythmic drugs, recurs after D.C. shock. In this case temporary DDD pacing can be a reliable alternative treatment.