title: Specific bacterial genotypes of Mycobacterium tuberculosis cause extensive dissemination and brain infection in an experimental model.
abstract: Meningeal tuberculosis is a severe type of extrapulmonary disease, which is thought to begin with respiratory infection, followed by hematogenous dissemination and brain infection. Host genetic susceptibility factors and specific mycobacterial substrains could be involved in its development. From an epidemiological study in Colombia, we selected three Mycobacterium tuberculosis clinical strains isolated from the cerebrospinal fluid (CSF) of patients with meningeal tuberculosis, and used them to infect BALB/c mice through the intratracheal route. These strains showed a distinctive spoligotype pattern. The course of infection in terms of strain virulence (mice survival, bacillary loads in lungs), bacilli dissemination and extrapulmonary infection (bacilli loads in blood, brain, liver, kidney and spleen), and immune responses (cytokine expression determined by real time PCR in brain and lung) was studied and compared with that induced by the laboratory strain H37Rv and other five clinical strains isolated from patients with pulmonary TB. All the clinical isolates from meningeal TB patients disseminated extensively through the hematogenous route infecting the brain, producing inflammation in the cerebral parenchyma and meninges, whereas H37Rv and clinical isolates from pulmonary TB patients showed very limited efficiency to infect the brain. Thus, it seems that mycobacterial strains with a distinctive genotype are able to disseminate extensively after the respiratory infection and infect the brain.
authors.affiliation: Department of Pathology, National Institute of Medical Sciences, Mexico City, Mexico. rhdezpando@hotmail.com
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez Pando
authors.forename: Diana
authors.initials: D
authors.lastname: Aguilar
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cohen
authors.forename: Martha
authors.initials: M
authors.lastname: Guerrero
authors.forename: Wellman
authors.initials: W
authors.lastname: Ribon
authors.forename: Patrícia
authors.initials: P
authors.lastname: Acosta
authors.forename: Hector
authors.initials: H
authors.lastname: Orozco
authors.forename: Brenda
authors.initials: B
authors.lastname: Marquina
authors.forename: Citlal
authors.initials: C
authors.lastname: Salinas
authors.forename: Daniel
authors.initials: D
authors.lastname: Rembao
authors.forename: Clara
authors.initials: C
authors.lastname: Espitia
mesh_terms: D000328:Adult; D000818:Animals; D058491:Bacterial Load; D003105:Colombia / Q000453:epidemiology; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005798:Genes, Bacterial; D005838:Genotype; D006801:Humans; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity; D014390:Tuberculosis, Meningeal / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: D016207:Cytokines