An Isoniazid Analogue Promotes <em>Mycobacterium tuberculosis</em>-Nanoparticle Interactions and Enhances Bacterial Killing by Macrophages
2012
de Faria, Tatiany J. | Roman, Mariane | de Souza, Nicole M. | de Vecchi, Rodrigo | de Assis, João Vitor | Gomes dos Santos, Ana Lùcia | Bechtold, Ivan H. | Winter, Nathalie | Soares, Maurilio José | Silva, Luciano Paulino | de Almeida, Mauro V. | Báfica, André | Universidade Federal de Santa Catarina ; Partenaires INRAE | Universidade Federal de Juiz de Fora (UFJF) | Infectiologie et Santé Publique (UMR ISP) ; Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT) | Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ) ; Pasteur Network (Réseau International des Instituts Pasteur) | Empresa Brasileira de Pesquisa Agropecuária (Embrapa) ; Ministério da Agricultura, Pecuária e Abastecimento [Brasil] (MAPA) ; Governo do Brasil-Governo do Brasil | CAPES/NANOBIOTEC (NANOTB 23038.021356 and 23038.019088 and NANOBIOMED 705/2009), CNPq (Universal 477857, 507205, and 576948)
International audience
Show more [+] Less [-]English. Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.
Show more [+] Less [-]Bibliographic information
This bibliographic record has been provided by Institut national de la recherche agronomique