title: The adenylyl cyclase Rv2212 modifies the proteome and infectivity of Mycobacterium bovis BCG.
abstract: All organisms have the capacity to sense and respond to environmental changes. These signals often involve the use of second messengers such as cyclic adenosine monophosphate (cAMP). This second messenger is widely distributed among organisms and coordinates gene expression related with pathogenesis, virulence, and environmental adaptation. Genomic analysis in Mycobacterium tuberculosis has identified 16 adenylyl cyclases (AC) and one phosphodiesterase, which produce and degrade cAMP, respectively. To date, ten AC have been biochemically characterized and only one (Rv0386) has been found to be important during murine infection with M. tuberculosis. Here, we investigated the impact of hsp60-driven Rv2212 gene expression in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) during growth in vitro, and during macrophage and mice infection. We found that hsp60-driven expression of Rv2212 resulted in an increased capacity of replication in murine macrophages but an attenuated phenotype in lungs and spleen when administered intravenously in mice. Furthermore, this strain displayed an altered proteome mainly affecting proteins associated with stress conditions (bfrB, groEL-2, DnaK) that could contribute to the attenuated phenotype observed in mice.
authors.affiliation: Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C., Col. Colinas de la Normal, 44270, Guadalajara, Jalisco, Mexico, cpedroza46@gmail.com.
authors.forename: César
authors.initials: C
authors.lastname: Pedroza-Roldán
authors.forename: Michel de Jesús
authors.initials: Mde J
authors.lastname: Aceves-Sánchez
authors.forename: Anisha
authors.initials: A
authors.lastname: Zaveri
authors.forename: Claudia
authors.initials: C
authors.lastname: Charles-Niño
authors.forename: Darwin Eduardo
authors.initials: DE
authors.lastname: Elizondo-Quiroga
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Hernández-Gutiérrez
authors.forename: Kirk
authors.initials: K
authors.lastname: Allen
authors.forename: Sandhya S
authors.initials: SS
authors.lastname: Visweswariah
authors.forename: Mario Alberto
authors.initials: MA
authors.lastname: Flores-Valdez
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D020543:Proteome; D000262:Adenylyl Cyclases