Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection

Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities

Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice

Background:Since antidopaminergic drugs are pharmacological agents employed in the management of gastrointestinal motor disorders at all ages, we investigated whether the enteric dopaminergic system may undergo developmental changes after birth.Methods:Intestinal mechanical activity was examined in vitro as changes in isometric tension.Results:In 2-d-old (P2) mice, dopamine induced a contractile effect, decreasing in intensity with age, replaced, at the weaning (day 20), by a relaxant response. Both responses were tetrodotoxin (TTX)-insensitive. In P2, dopaminergic contraction was inhibited by D1-like receptor antagonist and mimicked by D1-like receptor agonist. In 90-d-old (P90) mice, the relaxation was reduced by both D1- and D2-like receptor antagonists, and mimicked by D1- and D2-like receptor agonists. In P2, contraction was antagonized by phospholipase C inhibitor, while in P90 relaxation was antagonized by adenylyl cyclase inhibitor and potentiated by phospholipase C inhibitor. The presence of dopamine receptors was assessed by immunofluorescence. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed a significant increase in D1, D2, and D3 receptor expression in proximal intestine with the age.Conclusion:In mouse small intestine, the response to dopamine undergoes developmental changes shifting from contraction to relaxation at weaning, as the consequence of D2-like receptor recruitment and increased expression of D1 receptors

A comprehensive review of Toxoplasma gondii biology and host-cell interaction: Challenges for a plant-based vaccine

Toxoplasmosisis a worldwide-distributed infection caused by Toxoplasma gondii, which causes a wide range of clinical syndromesin humans, mammals and birds. T. gondiiis considered a parasite of veterinary and medical importance, because it maycause abortion or congenital disease in its intermediate hosts. Despite theeconomic losses associated with T. gondiiinfection in farm animals and the socio-economic impact caused by this zoonoticdisease in the human population, there is no effective treatment available forhumans or animals able to eliminate the parasite from the host once the chronicinfection has been established. The only commercial vaccine is the S48 strainof attenuated tachyzoites for use in sheep. However, this vaccine causes sideeffects, has a short life time and induces a short-term immunity. So far, noacellular vaccine against toxoplasmosis has been commercialized. In fact, futurechallenges include the development of an effective vaccine to preventtoxoplasmosis. Most parasitologists and vaccinologists agree that futureefforts should be concentrated on developing multi-antigen vaccines and moreefficient delivery systems able to express heterologous proteins abundantly aswell as on searching for immunization schedules and adequate adjuvants toenhance the protective responses. To achieve this, platforms for the productionof acellular vaccines based on the use of plants can have an important role.Fil: Sander, Valeria Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ángel, Sergio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Clemente, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentin

Recommendations to Prescribe in Complex Older Adults: Results of the CRIteria to Assess Appropriate Medication Use Among Elderly Complex Patients (CRIME) Project

The occurrence of several geriatric conditions may influence the efficacy and limit the use of drugs prescribed to treat chronic conditions. Functional and cognitive impairment, geriatric syndromes (i.e. falls or malnutrition) and limited life expectancy are common features of old age, which may limit the efficacy of pharmacological treatments and question the appropriateness of treatment. However, the assessment of these geriatric conditions is rarely incorporated into clinical trials and treatment guidelines. The CRIME (CRIteria to assess appropriate Medication use among Elderly complex patients) project is aimed at producing recommendations to guide pharmacologic prescription in older complex patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes, and providing physicians with a tool to improve the quality of prescribing, independent of setting and nationality. To achieve these aims, we performed the following: (i) Existing disease-specific guidelines on pharmacological prescription for the treatment of diabetes, hypertension, congestive heart failure, atrial fibrillation and coronary heart disease were reviewed to assess whether they include specific indications for complex patients; (ii) a literature search was performed to identify relevant articles assessing the pharmacological treatment of complex patients; (iii) A total of 19 new recommendations were developed based on the results of the literature search and expert consensus. In conclusion, the new recommendations evaluate the appropriateness of pharmacological prescription in older complex patients, translating the recommendations of clinical guidelines to patients with a limited life expectancy, functional and cognitive impairment, and geriatric syndromes. These recommendations cannot represent substitutes for careful clinical consideration and deliberation by physicians; the recommendations are not meant to replace existing clinical guidelines, but they may be used to help physicians in the prescribing process