Phosphate Uptake and Its Relation to Arsenic Toxicity in Lactobacilli.

The use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated with exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally low. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the transcriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention, plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP.

Ppx1 putative exopolyphosphatase is essential for polyphosphate accumulation in Lacticaseibacillus paracasei.

The linear polymer polyphosphate (poly-P) is present across all three domains of life and serves diverse physiological functions. The enzyme polyphosphate kinase (Ppk) is responsible for poly-P synthesis, whereas poly-P degradation is carried out by the enzyme exopolyphosphatase (Ppx). In many Lactobacillaceae, the Ppk-encoding gene (ppk) is found clustered together with two genes encoding putative exopolyphosphatases (ppx1 and ppx2) each having different domain compositions, with the gene order ppx1-ppk-ppx2. However, the specific function of these ppx genes remains unexplored. An in-frame deletion of ppx1 in Lacticaseibacillus paracasei BL23 resulted in bacteria unable to accumulate poly-P, whereas the disruption of ppx2 did not affect poly-P synthesis. The expression of ppk was not altered in the Δppx1 strain, and poly-P synthesis in this strain was only restored by expressing ppx1 in trans. Moreover, no poly-P synthesis was observed when ppk was expressed from a plasmid in the Δppx1 strain. Purified Ppx2 exhibited in vitro exopolyphosphatase activity, whereas no in vitro enzymatic activity could be demonstrated for Ppx1. This observation corresponds with the absence in Ppx1 of conserved motifs essential for catalysis found in characterized exopolyphosphatases. Furthermore, assays with purified Ppk and Ppx1 evidenced that Ppx1 enhanced Ppk activity. These results demonstrate that Ppx1 is essential for poly-P synthesis in Lc. paracasei and have unveiled, for the first time, an unexpected role of Ppx1 exopolyphosphatase in poly-P synthesis.IMPORTANCEPoly-P is a pivotal molecular player in bacteria, participating in a diverse array of processes ranging from stress resilience to pathogenesis while also serving as a functional component in probiotic bacteria. The synthesis of poly-P is tightly regulated, but the underlying mechanisms remain incompletely elucidated. Our study sheds light on the distinctive role played by the two exopolyphosphatases (Ppx) found in the Lactobacillaceae bacterial group, of relevance in food and health. This particular group is noteworthy for possessing two Ppx enzymes, supposedly involved in poly-P degradation. Remarkably, our investigation uncovers an unprecedented function of Ppx1 in Lacticaseibacillus paracasei, where its absence leads to the total cessation of poly-P synthesis, paralleling the impact observed upon eliminating the poly-P forming enzyme, poly-P kinase. Unlike the anticipated role as a conventional exopolyphosphatase, Ppx1 demonstrates an unexpected function. Our results added a layer of complexity to our understanding of poly-P dynamics in bacteria.

Arsenic Trioxide: Pharmacological Applications / Trióxido de Arsénico: Aplicaciones farmacológicas

Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results:Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1. Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

Antecedentes: El trióxido de arsénico es un compuesto químico que se ha utilizado como tratamiento de diversas enfermedades. A pesar de ser potencialmente tóxico, este compuesto se ha utilizado como terapia para tratar la leucemia mieloide aguda y se está investigando como posible tratamiento para diferentes tipos de cáncer. Objetivos: La presente revisión pretende describir el uso del trióxido de arsénico como posible agente terapéutico para la leucemia mieloide aguda, la leucemia promielocítica aguda, la leucemia mieloide crónica, el mieloma múltiple, el síndrome mielodisplásico, el carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de mama, la hepatitis C aplásica y el VIH-1. Métodos: Se realizó una revisión sistemática utilizando bases de datos (Elsevier, Google Scholar, PubMed) para recopilar documentos publicados antes de diciembre de 2023. Resultados: Se ha informado de múltiples aplicaciones farmacológicas del trióxido de arsénico para tratar la leucemia mieloide aguda y la leucemia mieloide crónica. Se ha demostrado que el trióxido de arsénico inhibe la angiogénesis, lo que resulta útil para el tratamiento del mieloma múltiple. Varios estudios han demostrado y sugerido la eficacia del trióxido de arsénico como tratamiento del carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de próstata, el cáncer de mama, la anemia aplásica, la hepatitis C y el VIH-1. Conclusión: A pesar de tener un efecto potencialmente tóxico, los compuestos de arsénico destacan como agentes terapéuticos para múltiples enfermedades, desde la sífilis hasta el cáncer. En los últimos años, se han investigado formas más eficientes de administrar y encontrar la dosis específica para poder tratar la enfermedad, causando los menores efectos adversos posibles.

Formulation and antimicrobial activity evaluation of a 0. 2% chlorhexidine canine mouthwash with essential oils / Formulación y evaluación de la actividad antimicrobiana de un enjuague bucal canino de clorhexidina al 2% y aceites esenciales

Background: Periodontal disease is the infection and inflammation of the gums, bones, and tissues involved in teeth support, and it is one of the most common diseases affecting pet dogs. Essential oils have shown antimicrobial activity against bacteria causing periodontal disease; therefore, they are considered potential therapeutic agents. Objectives: The main objective was to formulate and evaluate the antimicrobial activity of a 0.2% chlorhexidine canine mouthwash with essential oils. Methods: Three microemulsion formulations were obtained by constructing a pseudo-ternary phase diagram using the phase titration method. Different surfactant agents were evaluated, and hydrogenated castor oil was selected as the emulsifier agent. The antimicrobial activity of oregano essential oil (Origanum vulgare), thyme essential oil (Thymus vulgaris), and the three formulations were evaluated against Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius, and Escherichia coli. Results: Pure thyme and oregano essential oils showed higher antimicrobial activity than a 0,2% chlorhexidine solution. The formulations with essential oils plus chlorhexidine and chlorhexidine alone showed antimicrobial activity. The formulation containing only essential oils did not show antimicrobial activity. Conclusions: A canine mouthwash was formulated with chlorhexidine and thyme, and oregano essential oil. Based on the evaluation of antimicrobial activity, two of the proposed formulations could be a therapeutic option to reduce the risk and prevent periodontal disease in canines

Antecedentes: La enfermedad periodontal es la infección e inflamación de las encías, huesos y tejidos que brindan soporte a los dientes, es una de las enfermedades más comunes que afectan a los perros de compañía. Los aceites esenciales han mostrado actividad antimicrobiana contra las bacterias que causan la enfermedad periodontal; por lo tanto, son considerados como potenciales agentes terapéuticos. Objetivos: El objetivo principal de este trabajo fue formular y evaluar la actividad antimicrobiana de un colutorio canino de clorhexidina al 0,2% con aceites esenciales. Métodos: Se obtuvo tres formulaciones en microemulsión mediante la construcción de un diagrama de fase pseudoternario por el método de titulación de fase. Se evaluaron diferentes tensioactivos y se seleccionó el aceite de ricino hidrogenado como agente emulsificante de la formulación. La actividad antimicrobiana del aceite esencial de orégano (Origanum vulgare), el aceite esencial de tomillo (Thymus vulgaris) y las tres formulaciones fue evaluada contra Staphylococcus aureus, Streptococcus mutans, Streptococcus salivarius y Escherichia coli. Resultados: Los aceites esenciales puros de tomillo y orégano mostraron una mayor actividad antimicrobiana que una solución de clorhexidina al 0,2%. Las formulaciones con aceites esenciales más clorhexidina y únicamente clorhexidina mostraron actividad antimicrobiana. Mientras que la formulación que contiene solo aceites esenciales no mostró actividad antimicrobiana. Conclusión: Se formuló un enjuague bucal canino con clorhexidina y aceite esencial de tomillo y orégano. Según la evaluación de la actividad antimicrobiana, dos de las formulaciones propuestas podrían ser una opción terapéutica para disminuir el riesgo y prevenir la enfermedad periodontal en caninos