title: Antimicrobial peptides as novel anti-tuberculosis therapeutics.
abstract: Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, has recently joined HIV/AIDS as the world's deadliest infectious disease, affecting around 9.6 million people worldwide in 2014. Of those, about 1.2 million died from the disease. Resistance acquisition to existing antibiotics, with the subsequent emergence of Multi-Drug Resistant mycobacteria strains, together with an increasing economic burden, has urged the development of new anti-TB drugs. In this scope, antimicrobial peptides (AMPs), which are small, cationic and amphipathic peptides that make part of the innate immune system, now arise as promising candidates for TB treatment. In this review, we analyze the potential of AMPs for this application. We address the mechanisms of action, advantages and disadvantages over conventional antibiotics and how problems associated with its use may be overcome to boost their therapeutic potential. Additionally, we address the challenges of translational development from benchside to bedside, evaluate the current development pipeline and analyze the expected global impact from a socio-economic standpoint. The quest for more efficient and more compliant anti-TB drugs, associated with the great therapeutic potential of emerging AMPs and the rising peptide market, provide an optimal environment for the emergence of AMPs as promising therapies. Still, their pharmacological properties need to be enhanced and manufacturing-associated issues need to be addressed.
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal. Electronic address: jpsilva@deb.uminho.pt.
authors.forename: João P
authors.initials: JP
authors.lastname: Silva
authors.affiliation: Department of Immunophysiology, University of Porto, 4050-313 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal. Electronic address: fmgama@deb.uminho.pt.
authors.forename: Francisco Miguel
authors.initials: FM
authors.lastname: Gama
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents; D002460:Cell Line; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents
keywords: Antibiotics; Antimicrobial peptides; Mycobacteria; Peptide market; Pharmacoeconomical analysis; Tuberculosis