title: An Experimental Model for the Rapid Screening of Compounds with Potential Use Against Mycobacteria.
abstract: Infections caused by Mycobacterium tuberculosis and other mycobacteria are major challenges for global public health. Particularly worrisome are infections caused by multidrug-resistant bacteria, which are increasingly difficult to treat because of the loss of efficacy of the current antibacterial agents, a problem that continues to escalate worldwide. There has been a limited interest and investment on the development of new antibacterial agents in the past decades. This has led to the current situation, in which there is an urgent demand for innovative therapeutic alternatives to fight infections caused by multidrug-resistant pathogens, such as multidrug-resistant tuberculosis. The identification of compounds that can act as adjuvants in antimycobacterial therapeutic regimens is an appealing strategy to restore the efficacy lost by some of the antibiotics currently used and shorten the duration of the therapeutic regimen. In this work, by setting Mycobacterium smegmatis as a model organism, we have developed a methodological strategy to identify, in a fast and simple approach, compounds with antimycobacterial activity or with potential adjuvant properties, by either inhibition of efflux or other unrelated mechanisms. Such an approach may increase the rate of identification of promising molecules, to be further explored in pathogenic models for their potential use either as antimicrobials or as adjuvants, in combination with available therapeutic regimens for the treatment of mycobacterial infections. This method allowed us to identify a new molecule that shows promising activity as an efflux inhibitor in M. smegmatis.
authors.affiliation: 1 Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa , UNL, Lisbon, Portugal .
authors.forename: Sofia Santos
authors.initials: SS
authors.lastname: Costa
authors.affiliation: 1 Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa , UNL, Lisbon, Portugal .
authors.forename: Elizeth
authors.initials: E
authors.lastname: Lopes
authors.affiliation: 2 P4T group, Department of Pharmacy, University of Parma , Parma, Italy .
authors.forename: Elisa
authors.initials: E
authors.lastname: Azzali
authors.affiliation: 1 Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa , UNL, Lisbon, Portugal .
authors.forename: Diana
authors.initials: D
authors.lastname: Machado
authors.affiliation: 3 Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande , Rio Grande, Brazil .
authors.forename: Tatiane
authors.initials: T
authors.lastname: Coelho
authors.affiliation: 3 Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande , Rio Grande, Brazil .
authors.forename: Pedro Eduardo Almeida
authors.initials: PE
authors.lastname: da Silva
authors.affiliation: 1 Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa , UNL, Lisbon, Portugal .
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.affiliation: 2 P4T group, Department of Pharmacy, University of Parma , Parma, Italy .
authors.forename: Marco
authors.initials: M
authors.lastname: Pieroni
authors.affiliation: 1 Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa , UNL, Lisbon, Portugal .
authors.forename: Isabel
authors.initials: I
authors.lastname: Couto
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D008962:Models, Theoretical; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents
keywords: adjuvant; antimycobacterial; compound; efflux inhibitor; mycobacteria; screening