Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

An Isoniazid Analogue Promotes Mycobacterium tuberculosis-Nanoparticle Interactions and Enhances Bacterial Killing by Macrophages

2012; American Society for Microbiology; Volume: 56; Issue: 5 Linguagem: Inglês

10.1128/aac.05993-11

1098-6596

Tatiany J. de Faria, Mariane Roman, Nicole Menezes de Souza, Rodrigo De Vecchi, João Vítor de Assis, Ana L. Santos, Ivan H. Bechtold, Nathalie Winter, Maurílio José Soares, Luciano Paulino Silva, Mauro Vieira de Almeida, André Báfica,

Inhalation and Respiratory Drug Delivery

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.