Periodically Disturbing the Spatial Structure of Biofilms Can Affect the Production of an Essential Virulence Factor in Pseudomonas aeruginosa

Understanding the environmental factors that affect the production of virulence factors has major implications in evolution and medicine. While spatial structure is important in virulence factor production, observations of this relationship have occurred in undisturbed or continuously disturbed environments. However, natural environments are subject to periodic fluctuations, including changes in physical forces, which could alter the spatial structure of bacterial populations and impact virulence factor production. Using Pseudomonas aeruginosa PA14, we periodically applied a physical force to biofilms and examined production of pyoverdine. Intermediate frequencies of disturbance reduced the amount of pyoverdine produced compared to undisturbed or frequently disturbed conditions. To explore the generality of this finding, we examined how an intermediate disturbance frequency affected pyoverdine production in 21 different strains of P. aeruginosa. Periodic disturbance increased, decreased, or did not change the amount of pyoverdine produced relative to undisturbed populations. Mathematical modeling predicts that interactions between pyoverdine synthesis rate and biofilm density determine the amount of pyoverdine synthesized. When the pyoverdine synthesis rates are high, depletion of the biofilm due to disturbance reduces the accumulation of pyoverdine. At intermediate synthesis rates, production of pyoverdine increases during disturbance as bacteria dispersed into the planktonic state enjoy increased growth and pyoverdine production rates. At low synthesis rates, disturbance does not alter the amount of pyoverdine produced since disturbance-driven access to nutrients does not augment pyoverdine synthesis. Our results suggest that environmental conditions shape robustness in the production of virulence factors and may lead to novel approaches to treat infections

Original article title: "Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial"

<p>Abstract</p> <p>Background</p> <p>Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo.</p> <p>Methods</p> <p>This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid.</p> <p>Results</p> <p>The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively.</p> <p>Conclusion</p> <p>Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo.</p> <p>Trial Registration</p> <p>chiCTRTRC10000930</p

Recombination as an Enforcement Mechanism of Prosocial Behavior in Cooperating Bacteria

Prosocial behavior is ubiquitous in nature despite the relative fitness costs carried by cooperative individuals. However, the stability of cooperation in populations is fragile and often maintained through enforcement. We propose that homologous recombination provides such a mechanism in bacteria. Using an agent-based model of recombination in bacteria playing a public goods game, we demonstrate how changes in recombination rates affect the proportion of cooperating cells. In our model, recombination converts cells to a different strategy, either freeloading (cheaters) or cooperation, based on the strategies of neighboring cells and recombination rate. Increasing the recombination rate expands the parameter space in which cooperators outcompete freeloaders. However, increasing the recombination rate alone is neither sufficient nor necessary. Intermediate benefits of cooperation, lower population viscosity, and greater population size can promote the evolution of cooperation from within populations of cheaters. Our findings demonstrate how recombination influences the persistence of cooperative behavior in bacteria

Postoperative morbidity is an additional prognostic factor after potentially curative pancreaticoduodenectomy for primary duodenal adenocarcinoma.

Postoperative morbidity is an additional prognostic factor after potentially curative pancreaticoduodenectomy for primary duodenal adenocarcinoma

Synthetically Engineered Microbes Reveal Interesting Principles of Cooperation

Cooperation is ubiquitous in biological systems. However, if natural selection favors traits that confer an advantage to one individual over another, then helping others would be paradoxical. Nevertheless, cooperation persists and is critical in maintaining homeostasis in systems ranging from populations of bacteria to groupings of mammals. Developing an understanding of the dynamics and mechanisms by which cooperation operates is critical in understanding ecological and evolutionary relationships. Over the past decade, synthetic biology has emerged as a powerful tool to study social dynamics. By engineering rationally controlled and modulatable behavior into microbes, we have increased our overall understanding of how cooperation enhances, or conversely constrains, populations. Furthermore, it has increased our understanding of how cooperation is maintained within populations, which may provide a useful framework to influence populations by altering cooperation. As many bacterial pathogens require cooperation to infect the host and survive, the principles developed using synthetic biology offer promise of developing novel tools and strategies to treat infections, which may reduce the use of antimicrobial agents. Overall, the use of engineered cooperative microbes has allowed the field to verify existing, and develop novel, theories that may govern cooperative behaviors at all levels of biology

Periodically Disturbing the Spatial Structure of Biofilms Can Affect the Production of an Essential Virulence Factor in

Understanding the environmental factors that affect the production of virulence factors has major implications in evolution and medicine. While spatial structure is important in virulence factor production, observations of this relationship have occurred in undisturbed or continuously disturbed environments. However, natural environments are subject to periodic fluctuations, including changes in physical forces, which could alter the spatial structure of bacterial populations and impact virulence factor production. Using Pseudomonas aeruginosa PA14, we periodically applied a physical force to biofilms and examined production of pyoverdine. Intermediate frequencies of disturbance reduced the amount of pyoverdine produced compared to undisturbed or frequently disturbed conditions. To explore the generality of this finding, we examined how an intermediate disturbance frequency affected pyoverdine production in 21 different strains of P. aeruginosa. Periodic disturbance increased, decreased, or did not change the amount of pyoverdine produced relative to undisturbed populations. Mathematical modeling predicts that interactions between pyoverdine synthesis rate and biofilm density determine the amount of pyoverdine synthesized. When the pyoverdine synthesis rates are high, depletion of the biofilm due to disturbance reduces the accumulation of pyoverdine. At intermediate synthesis rates, production of pyoverdine increases during disturbance as bacteria dispersed into the planktonic state enjoy increased growth and pyoverdine production rates. At low synthesis rates, disturbance does not alter the amount of pyoverdine produced since disturbance-driven access to nutrients does not augment pyoverdine synthesis. Our results suggest that environmental conditions shape robustness in the production of virulence factors and may lead to novel approaches to treat infections