Mammalian cells internalize bacteriophages and use them as a resource to enhance cellular growth and survival.

There is a growing appreciation that the direct interaction between bacteriophages and the mammalian host can facilitate diverse and unexplored symbioses. Yet the impact these bacteriophages may have on mammalian cellular and immunological processes is poorly understood. Here, we applied highly purified phage T4, free from bacterial by-products and endotoxins to mammalian cells and analyzed the cellular responses using luciferase reporter and antibody microarray assays. Phage preparations were applied in vitro to either A549 lung epithelial cells, MDCK-I kidney cells, or primary mouse bone marrow derived macrophages with the phage-free supernatant serving as a comparative control. Highly purified T4 phages were rapidly internalized by mammalian cells and accumulated within macropinosomes but did not activate the inflammatory DNA response TLR9 or cGAS-STING pathways. Following 8 hours of incubation with T4 phage, whole cell lysates were analyzed via antibody microarray that detected expression and phosphorylation levels of human signaling proteins. T4 phage application led to the activation of AKT-dependent pathways, resulting in an increase in cell metabolism, survival, and actin reorganization, the last being critical for macropinocytosis and potentially regulating a positive feedback loop to drive further phage internalization. T4 phages additionally down-regulated CDK1 and its downstream effectors, leading to an inhibition of cell cycle progression and an increase in cellular growth through a prolonged G1 phase. These interactions demonstrate that highly purified T4 phages do not activate DNA-mediated inflammatory pathways but do trigger protein phosphorylation cascades that promote cellular growth and survival. We conclude that mammalian cells are internalizing bacteriophages as a resource to promote cellular growth and metabolism.

The gut virome and the relevance of temperate phages in human health.

Alterations in the gut virome impact human health. Bacteriophages, viruses that infect bacteria, dominate the gut virome and are mainly composed by virulent and temperate phages. While virulent phages exclusively replicate within and lyse their bacterial host's cell, temperate phages switch from an integrated state residing within their bacterial host's chromosome to an induced free virion state via an induction event. How often do these induction events occur and what are their implications on gut homeostasis? Here, we summarize the current knowledge of the gut virome based on metagenomics and present how the proportion of induced temperate phages varies amongst individuals, age, and disease states. Finally, we highlight the importance of building upon classical culture-dependent techniques and sequencing approaches to improve our understanding of temperate phages to enable their potential therapeutic use.

Phages to shape the gut microbiota?

The concept of (bacterio)phage therapy is simple; target the phage to the bacterial pathogen causing disease. As phages are natural killers of bacteria, one could expect this to be an easy task. However, when it comes to phage therapy within the gut, it might not be quite that simple. Already without exogenous intervention, a multitude of phage-bacterial interactions occur within the human gut, some of which might play a direct role in disease progression. In this perspective, we aim to summarise the current understanding of phages within our gut, moving from infancy, adulthood, and then into disease progression. We then highlight recent advances in phage-based interventions, both conventional phage therapy and the progressing field of whole virome transplant.

Bacteriophage uptake by mammalian cell layers represents a potential sink that may impact phage therapy.

It is increasingly apparent that bacteriophages, viruses that infect bacteria and more commonly referred to as simply phages, have tropisms outside their bacterial hosts. Using live tissue culture cell imaging, we demonstrate that cell type, phage size, and morphology play a major role in phage internalization. Uptake was validated under physiological conditions using a microfluidic device. Phages adhered to mammalian tissues, with adherent phages being subsequently internalized by macropinocytosis, with functional phages accumulating intracellularly. We incorporated these results into a pharmacokinetic model demonstrating the potential impact of phage accumulation by cell layers, which represents a potential sink for circulating phages in the body. During phage therapy, high doses of phages are directly administered to a patient in order to treat a bacterial infection, thereby facilitating broad interactions between phages and mammalian cells. Understanding these interactions will have important implications on innate immune responses, phage pharmacokinetics, and the efficacy of phage therapy.

Scientometric analysis of Colombian research on bio-inoculants for agricultural production / Análisis cienciométrico de investigación colombiana en bio-inoculantes para producción agrícola / Análise cientométrica das pesquisas colombianas em bioinoculantes para a produção agrícola

The excessive use of synthetic chemical inputs in agricultural production has led to the disruption of biogeochemical cycles. One of the alternatives that arose within the systems of sustainable agriculture was the partial or total replacement of chemicals by biological substances. The analysis of relevant scientific literature has become a tool for assessing the quality of knowledge generation and its impact on the environment. A scientometric analysis was conducted of Colombian research on bio-inoculants from 2009 through 2014 in journals added to the Web of SciencesTM in order to identify the characteristics of the main target crops, the microorganisms used, and the beneficial effects on agriculture. In this work, 34 articles were identified: 24 (71 %) were research on bio-fertilizer development and 10 (29 %) on bio-pesticides. Articles mainly focused on the study of Gram-negative bacilli affecting the area (77 %), while others focused on issues and topics surrounding vegetables (30 %).The analysis of co-occurrence of keywords identified: i. several genera of microorganisms (e.g. A%otobacter sp., Bradyrhi%obium sp.) and sustainable agriculture as issues that have a leading role in this scientific field, ii. plant growth promoting rhizobacteria (PGPR) as an emerging issue, iii. biological nitrogen fixation (BNF) as a subject which has risen in a complementary manner and iv. endophytic bacteria and biodiversity as issues in growth. This study showed that research in Colombia could be targeted on issues such as endophytic bacteria, diversity and productivity.

El uso excesivo de insumos sintéticos en la producción agrícola ha llevado a la disrupción de los ciclos biogeoquímicos. Como alternativa a este problema, los sistemas de agricultura sostenible han reemplazado parcial o totalmente los químicos por sustancias biológicas. El análisis de literatura científica relevante se ha convertido en una herramienta para determinar la calidad de la generación de conocimiento en este campo y su impacto en el ambiente.Se llevó a cabo un análisis cienciométrico de la investigación en Colombia sobre bioinoculantes entre 2009 y 2014. Se tuvieron en cuenta revistas indizadas en la Red de Ciencias®. Se buscó identificar las características de los principales cultivos, los microorganismos utilizados y sus efectos benéficos en la agricultura. Se seleccionaron 34 artículos: 24 (71%) sobre desarrollo de biofertilizantes y 10 (29%) sobre biopesticidas. Los artículos se enfocaron principalmente en el estudio de bacilos Gram-negativos (77%), mientras que otros se enfocaron en los temas relativos a hortalizas (30%). El análisis de co-ocurrencia de palabras claves identificó: i. Algunos géneros de microorganismos (Azptobacter sp., Bradyrhizobium sp.) y la agricultura sostenible como temas relevantes en este campo, ii. Rizobacterias promotoras del crecimiento en plantas (PGPR) como un tópico emergente, iii. Fijación biológica de nitrógeno (FBN) como un tema emergente y complementario y iv. Bacterias endofíticas y biodiversidad como tópicos en crecimiento. Este estudio mostró también que la investigación en Colombia podría enfocarse en temas como bacterias endofíticas, diversidad y productividad.

O uso excessivo de produtos químicos sintéticos na produção agrícola levou a uma perturbação dos ciclos biogeoquímicos. Uma das alternativas que surgiram dentro dos sistemas de agricultura sustentável foi a substituição total ou parcial de compostos químicos por substancias biológicas. O estudo de literatura científica relevante se tornou uma ferramenta para avaliar a qualidade da geração de conhecimento e seu impacto no meio ambiente. A análise cientométrica foi realizada em investigacoes colombianas sobre bioinoculantes de 2009 a 2014, em revistas disponíveis em Web of ScienceTM, com o intuito de identificar as características das principais culturas alvos, os microorganismos utilizados, e o efeito benéfico na agricultura. Neste trabalho, 34 artigos foram identificados: 24 (71 %) eram pesquisas sobre o desenvolvimiento de biofertilizantes e 10 (29 %) sobre biopesticidas. Os artigos eram focados principalmente no estudo de bacilos Gram-negativos afetando a área (77 %), enquanto que outros eram voltados a questoes e temas de vegetais (30 %). A análise de coocorréncia de palavras-chave identificou: i. diversos géneros de microorganismos (Ex. Azptobacter sp., Bradyrhizpbium sp.) e agricultura sustentável como questóes fundamentais nesta área científica, ii. rizobactéricas promotoras de crescimento de plantas (PGPR) como um tema emergente, iii. fixação biológica de nitrogénio (BNF) como um assunto que tem surgido de maneira complementar e iv. bactérias endofíticas e biodiversidade como temas em crescimento. Este estudo mostrou que a pesquisa na Colombia poderia ser dirigida a questoes como bactérias endofíticas, diversidade e produtividade.