Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

Development and Preliminary Validation of a Rabbit Model of Duodenal Atresia for Training in Pediatric Surgical Skills.

Duodenal atresia is a congenital defect that requires advanced surgical skills. The objective of this study is to present an anatomical defect of duodenal atresia using a rabbit model and evaluate the preliminary experience for the training of surgical skills with pediatric surgeons. Adult white New Zealand male rabbits weighing 3.0 to 4.5 kg were used to create the defect. To simulate the bottom of the dilated blind pouch, the gastric antrum of the rabbit was obliterated using a 2-0 Prolene suture, and the cecal appendix was dissected to simulate the continuation of the duodenum. Participants performed laparoscopic duodenal atresia repair in this animal model using the iPhone trainer. Thirteen pediatric surgeons with experience in laparoscopic duodenal atresia repair assessed this model with a questionnaire on 5-point Likert-type scale. Overall, the simulated model of duodenal atresia obtained a general average score of 4.39. The highest observed average was for its physical realism, whereas the lowest score was in surgical experience. The global opinion of the model obtained a score of 4.40. In addition, all surgeons answered that this rabbit model showed the same complexity as newborns and young children in the repair of this type of defect. The inclusion of new models through rabbits in pediatric surgery programs will allow the development of advanced skills of pediatric residents and surgeons.

Bactofection of sequences encoding a Bax protein peptide chemosensitizes prostate cancer tumor cells / Bactofección de secuencias que codifican para un péptido de la proteína Bax quimiosensibiliza a células tumorales de cáncer de próstata

Abstract: Background: Tumor cell resistance to chemotherapy agents is one of the main problems in the eradication of different neoplasias. One of the mechanisms of this process is the overexpression of anti-apoptotic proteins such as Bcl-2 and Bcl-XL; blocking the activity of these proteins may contribute to the sensitization of tumor cells and allow the adequate effects of chemotherapeutic drugs. Methods and results: This study adressed the transfection of prostate cancer cells (PC3) with a plasmid encoding a recombinant protein with an antagonist peptide from the BH3 region of the Bax protein fused to the GFP reporter protein (BaxGFP). This protein induced apoptosis of these tumor cells; further, selective transport of this plasmid to the tumor cell with Salmonella enterica serovar Typhimurium (strain SL3261), a live-attenuated bacterial vector, can induce sensitization of the tumor cell to the action of drugs such as cisplatin, through a process known as bactofection. Conclusions: These results suggest that Salmonella enterica can be used as a carrier vector of nucleotide sequences encoding heterologous molecules used in antitumor therapy.

Resumen: Introducción: La resistencia a los agentes quimioterapéuticos por parte de las células tumorales es uno de los principales problemas para la erradicación de distintas neoplasias. Uno de los mecanismos involucrados en este proceso es la sobreexpresión de proteínas antiapoptóticas como Bcl-2 y Bcl-XL. El bloquear la actividad de estas proteínas puede contribuir a la sensibilización de las células tumorales, permitiendo que los fármacos quimioterapeúticos funcionen de forma adecuada. Métodos y resultados: En este trabajo se llevó a cabo la transfección de células de cáncer de próstata (PC3) por un plásmido que codifica para una proteína recombinante que contiene un péptido antagónico perteneciente a la región BH3 de la proteína Bax fusionada a la proteína reportera GFP (BaxGFP). Esta proteína fue capaz de inducir apoptosis en las células PC3. El transporte selectivo de este plásmido hacia la célula tumoral empleando Salmonella enterica serovar Typhimurium cepa SL3261, un vector bacteriano vivo atenuado, permitió la sensibilización de la célula tumoral a la acción de fármacos como el cisplatino mediante un proceso denominado bactofección. Conclusiones: Estos resultados sugieren que Salmonella enterica puede emplearse como un vector acarreador de secuencias nucleotídicas que codifican para moléculas heterólogas empleadas en la terapia antitumoral.

Bactofection of sequences encoding a Bax protein peptide chemosensitizes prostate cancer tumor cells.

BACKGROUND: Tumor cell resistance to chemotherapy agents is one of the main problems in the eradication of different neoplasias. One of the mechanisms of this process is the overexpression of anti-apoptotic proteins such as Bcl-2 and Bcl-XL; blocking the activity of these proteins may contribute to the sensitization of tumor cells and allow the adequate effects of chemotherapeutic drugs. METHODS AND RESULTS: This study adressed the transfection of prostate cancer cells (PC3) with a plasmid encoding a recombinant protein with an antagonist peptide from the BH3 region of the Bax protein fused to the GFP reporter protein (BaxGFP). This protein induced apoptosis of these tumor cells; further, selective transport of this plasmid to the tumor cell with Salmonella enterica serovar Typhimurium (strain SL3261), a live-attenuated bacterial vector, can induce sensitization of the tumor cell to the action of drugs such as cisplatin, through a process known as bactofection. CONCLUSIONS: These results suggest that Salmonella enterica can be used as a carrier vector of nucleotide sequences encoding heterologous molecules used in antitumor therapy.