title: Exploring the contribution of mycobacteria characteristics in their interaction with human macrophages.
abstract: Tuberculosis (TB) is a major health problem. The emergence of multidrug resistant (MDR) Mycobacterium tuberculosis (Mtb) isolates confounds treatment strategies. In Portugal, cases of MDR-TB are reported annually with an increased incidence noted in Lisbon. The majority of these MDR-TB cases are due to closely related mycobacteria known collectively as the Lisboa family and Q1 cluster. Genetic determinants linked to drug resistance have been exhaustively studied resulting in the identification of family and cluster specific mutations. Nevertheless, little is known about other factors involved in development of mycobacteria drug resistance. Here, we complement genetic analysis with the study of morphological and structural features of the Lisboa family and Q1 cluster isolates by using scanning and transmission electron microscopy. This analysis allowed the identification of structural differences, such as cell envelope thickness, between Mtb clinical isolates that are correlated with antibiotic resistance. The infection of human monocyte derived macrophages allowed us to document the relative selective advantage of the Lisboa family isolates over other circulating Mtb isolates.
authors.affiliation: Centro de Patogénese Molecular, URIA, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Silva
authors.forename: Joao
authors.initials: J
authors.lastname: Perdigao
authors.forename: Elsa
authors.initials: E
authors.lastname: Alverca
authors.forename: António P Alves
authors.initials: AP
authors.lastname: de Matos
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Carvalho
authors.forename: Isabel
authors.initials: I
authors.lastname: Portugal
authors.forename: Luisa
authors.initials: L
authors.lastname: Jordao
mesh_terms: D002473:Cell Wall / Q000648:ultrastructure*; D024881:Drug Resistance, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000648:ultrastructure*; D011174:Portugal; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology