title: Potential Mechanism of Action of 3'-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus.
abstract: Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N Ciudad Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, Mexico. jackman610@msn.com.|Facultad de Ciencia Químicas, Universidad Juárez del Estado de Durango, Av. Artículo 123 S/N, Núcleo Universitario, Col. Filadelfia, Gómez Palacio, Durango C.P. 35015, Mexico. jackman610@msn.com.
authors.forename: Juan Manuel J
authors.initials: JM
authors.lastname: Favela-Hernández
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N Ciudad Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, Mexico. aldo.clemente@alumnos.uaem.mx.
authors.forename: Aldo F
authors.initials: AF
authors.lastname: Clemente-Soto
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N Ciudad Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, Mexico. isaias.balderasrn@uanl.edu.mx.
authors.forename: Isaías
authors.initials: I
authors.lastname: Balderas-Rentería
authors.affiliation: Servicio de Gastroenterología y Departamento de Patología Clínica, Hospital Universitario, Dr. José Eleuterio González. Madero y Aguirre Pequeño, Universidad Autónoma de Nuevo León, Mitras Centro, Monterrey, Nuevo León C.P. 64460, Mexico. elvira_garza_gzz@yahoo.com.
authors.forename: Elvira
authors.initials: E
authors.lastname: Garza-González
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N Ciudad Universitaria, San Nicolás de los Garza, Nuevo León C.P. 66451, Mexico. maria.camachocn@uanl.edu.mx.
authors.forename: María del Rayo
authors.initials: Mdel R
authors.lastname: Camacho-Corona
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D032442:Larrea / Q000737:chemistry*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009284:Naphthols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D018515:Plant Leaves / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C000606930:3'-demethoxy-6-O-demethylisoguaiacin; D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017705:Lignans; D009284:Naphthols
keywords: 3′-demethoxy-6-O-demethylisoguaiacin; Larrea tridentata; methicillin-resistant Staphylococcus aureus; microarrays; mode of action; real time PCR