Search

The inappropriate use of antibiotics has led to an increase in the rate of bacterialresistance, therefore, the study of new compounds with bioactive propertieshas been essential to face the challenge caused by the lack of effective drugsfor the treatment of infections caused by a wide range of bacteria. In this sense,the present research work focuses on the computational modeling of Cruzio-septin CC-17 belonging to the family of peptides extracted from the exudate ofthe Cruziohyla calcariferfrog. Initially, the characterization of the peptide wascarried out based on its physicochemical properties and the elucidation of itssecondary structure. In addition, molecular docking was performed to analyzethe activity of the different enzymes present in Escherichia coli, Staphylococcusaureusand Candida albicansand with molecules present in the bacterial cell membrane. The results show that Cruzioseptin CC-17 is a peptide which se-condary structure is predominantly composed of alpha helical regions and hasa net charge of +2 which gives it the basic character, has an isoelectric point of8.6 and is composed of a 52.7% by hydrophobic amino acids, which confirmsits cationic character. In the other hand, molecular docking results shows thatthe bioactivity of the peptide can be explained based on a concentrated attackmechanism on the bacterial cell membrane where the cell lysis occurs by theelectrostatic interactions between Cruzioseptin CC-17 with the different mole-cules of the cell membrane., El inadecuado uso de antibióticos ha conducido a un aumento en la tasa deresistencia bacteriana por esto ha sido fundamental el estudio de nuevos com-puestos con propiedades bioactivas que permitan enfrentar el desafío ocasionado por la falta de fármacos efectivos para el tratamiento de infecciones cau-sadas por un amplio rango de bacterias. En este sentido, el presente trabajo deinvestigación se centra en el modelamiento computacional de la CruzioseptinaCC-17 perteneciente a la familia de péptidos identificados en el exudado de larana Cruziohyla calcarifer. Inicialmente, se realizó la caracterización del pép-tido en función de sus propiedades fisicoquímicas y la elucidación de su es-tructura secundaria, asimismo, para analizar la actividad del péptido sedesarrolló el estudio de acoplamiento molecular de la Cruzioseptina CC-17con enzimas presentes en Escherichia coli, Staphylococcus aureus, Candida al-bicans y con moléculas pertenecientes a la membrana celular bacteriana. Losresultados muestran que la Cruzioseptina CC-17 es un péptido cuya estructurasecundaria está compuesta predominantemente por regiones alfa helicoidalesy presenta una carga de +2 lo cual le concede el carácter básico, presenta unpunto isoeléctrico de 8,6 y está compuesta en un 52,7 % por aminoácidos hi-drofóbicos. Finalmente, el estudio de acoplamiento molecular demuestra quela bioactividad del péptido puede explicarse en base a un mecanismo de ataquefocalizado en la membrana celular bacteriana en donde la lisis celular se logragracias a las interacciones electrostáticas entre la Cruzioseptina CC-17 con losdistintos componentes de la membrana bacteriana.

The increasing development of resistance to antibiotics by the microbial worldis a growing problem and in response new molecules with antimicrobial po-tential are being studied, among them antimicrobial peptides such as Cruzio-septins. This work presents a preliminary computational study of CruzioseptinCC-16 extracted from exudate from the skin of the frog Cruziohyla calcarifer.Based on the amino acid sequence of the peptide, different computational stu-dies were carried out, including the prediction of its physicochemical propertiesand its secondary structure. In addition to this, a molecular docking study ofCruzioseptin CC-16 was carried out with different enzymes of biological im-portance for microorganisms such asEscherichia coli, Staphylococcus aureus and Candida albicans,and with molecules present in the bacterial cell mem-brane. The results showed that Cruzioseptin CC-16 is a 23 residues long peptidewith a predominant alpha helical conformation, an isoelectric point of 10.73,a basic charge of +3 and a net charge at pH 7 of +3.1, in addition of havingmore than 50 % of its structure made up of hydrophobic amino acids, fittingthe definition of a cationic antimicrobial peptide. Preliminary molecular doc-king studies show that a mechanism of action based on enzyme inhibition isnot possible mainly due to the size of the peptide, while a mechanism basedon a concentrated attack on the microbial membrane may be viable due to theelectrostatic interactions of the Cruizoseptin CC-16 with different componentsof the membrane., El creciente desarrollo de resistencia a antibióticos por parte de mundo micro-biano es un problema cada vez mayor y en respuesta nuevas moléculas con potencial antimicrobiano están siendo estudiadas, entre ellas los péptidos an-timicrobianos como las Cruzioseptinas. Este trabajo presenta un estudio com-putacional preliminar de la Cruzioseptina CC-16 extraída del exudado de lapiel de la rana Cruziohyla calcarifer. Con base en la secuencia de aminoácidosdel péptido se llevaron a cabo diferentes estudios computacionales, entre ellos,la predicción de las propiedades fisicoquímicas y la estructura secundaria. Ade-más de esto se efectuó el acoplamiento molecular de la Cruzioseptina CC-16con diferentes enzimas de importancia biológica para microrganismos comoEscherechia coli, Staphylococcus aureusy Candida albicans,y con moléculaspresentes en la membrana celular bacteriana. Los resultados mostraron que laCruzioseptina CC-16 es un péptido de 23 residuos de largo con una confor-mación alfa helicoidal predominante, un punto isoeléctrico de 10,73, una cargade +3 de carácter básica y una carga neta a pH 7 de +3,1, además de tenermás del 50 % de su estructura conformada por aminoácidos hidrofóbicos, cla-sificando como un péptido antimicrobiano catiónico. Los estudios preliminaresde acoplamiento molecular muestran que un mecanismo de acción basado eninhibición enzimática no es posible, debido principalmente al tamaño del pép-tido, mientras que un mecanismo con base en un ataque concentrado en lamembrana microbiana puede ser viable, debido a las interacciones electrostá-ticas de la Cruzioseptina CC-16 con diferentes componentes de la membrana.

Bothrops atrox is the most clinically relevant snake species within the Amazon region, which includes Ecuadorian territories. It comprises a large distribution, which could contribute to the genetic and venomic variation identified in the species. The high variability and protein isoform diversity of its venom are of medical interest, since it can influence the clinical manifestations caused by envenomation and its treatment. However, in Ecuador there is insufficient information on the diversity of venomic phenotypes, even of relevant species such as B. atrox. Here, we characterized the biochemical and toxicological profiles of the venom of six B. atrox individuals from the Ecuadorian Amazon. Differences in catalytic activities of toxins, elution profiles in liquid chromatography, electrophoretic patterns, and toxic effects among the analyzed samples were identified. Nonetheless, in the preclinical testing of antivenom, two samples from Mera (Pastaza) required a higher dose to achieve total neutralization of lethality and hemorrhage. Taken together, these data highlight the importance of analyzing individual venoms in studies focused on the outcomes of envenoming

Fluoroquinolone resistance can be conferred through chromosomal mutations or by the acquisition of plasmids carrying genes such as the quinolone resistance gene (qnr). In this study, 3,309 strains of commensal Escherichia coli were isolated in Ecuador from: (i) humans and chickens in a rural northern coastal area (n = 2368, 71.5%) and (ii) chickens from an industrial poultry operation (n = 827, 25%). In addition, 114 fluoroquinolone-resistant strains from patients with urinary tract infections who were treated at three urban hospitals in Quito, Ecuador were analyzed. All of the isolates were subjected to antibiotic susceptibility screening. Fluoroquinolone-resistant isolates (FRIs) were then screened for the presence of qnrB genes. A significantly higher phenotypic resistance to fluoroquinolones was determined in E. coli strains from chickens in both the rural area (22%) and the industrial operation (10%) than in strains isolated from humans in the rural communities (3%). However, the rates of qnrB genes in E. coli isolates from healthy humans in the rural communities (11 of 35 isolates, 31%) was higher than in chickens from either the industrial operations (3 of 81 isolates, 6%) or the rural communities (7 of 251 isolates, 2.8%). The occurrence of qnrB genes in human FRIs obtained from urban hospitals was low (1 of 114 isolates, 0.9%). These results suggested that the qnrB gene is more widely distributed in rural settings, where antibiotic usage is low, than in urban hospitals and industrial poultry operations. The role of qnrB in clinical resistance to fluoroquinolones is thus far unknown. [Int Microbiol 2015; 18(2):85-90]Keywords: Escherichia coli · gene qnrB · quinolone resistance · urban hospitals · industral poultry operations