Prospective Tuberculosis Treatment: Peptides, Immunity and Autophagy

Abstract

Tuberculosis (TB) is a world-leading infectious disease caused by Mycobacterium tuberculosis (Mtb). The current treatment lasts 6 months and has contributed to the development of multidrug resistant (MDR) strains that nowadays cause almost half a million deaths around the globe. Forty years of research have rendered only 1 new drug to treat the new MDR strains. In the current review we present emerging trends to treat TB particularly focused on natural and synthetic peptides. The ability of some of these peptides to display multifunctional roles in TB treatment, particularly immune system modulation through autophagy and direct antimicrobial activity against Mtb, may present advantages to control the impact of this disease. We review the mechanisms of action relevant in the development of multifunctional peptides that may lead to evaluate new ways to treat TB, a disease that has accompanied human society for centuries

Host Antimicrobial Peptides: The Promise of New Treatment Strategies against Tuberculosis

“…Expression of endogenous AMPs represents one of the most ancient host defense strategy of living organisms. Their multifunctional mode of action, natural origin, and effectiveness at low concentration have positioned them as prospective candidates in future antitubercular therapeutics market ( 3 , 7 , 31 , 32 ). Notwithstanding, to ensure a successful therapy prior to drug design, we must deepen in the knowledge of the underlying mechanism of action of our own innate immunity players.…”

“…Autophagy has other beneficial effects for the host, such as the restriction of inflammation ( 58 ). Indeed, one of main currently used anti-TB drug is rapamycin, an autophagy activator, and the search of novel autophagy inducers is a priority ( 3 , 23 , 59 ).…”

“…Pro and anti-inflammatory effects can be induced by AMPs mediated by the release of a variety of cytokines ( 16 , 23 , 57 ). Interestingly, the same AMP can have a pro-inflammatory action at an early infection stage, while shifting to anti-inflammatory activity during late infection ( 3 ). Indeed, many immune factors play an essential role in the mediation of the infective process ( 8 ).…”

“…Despite the initial underestimation of the properties of antimicrobial peptides (AMPs) and the difficulties encountered in their attempt to reach the market, nowadays, it is widely accepted that AMPs are multifunctional molecules with key contributions in the mammalian host innate defense ( 2 , 3 , 16 , 17 ). In addition, due to the evolution of drug resistance among Mtb strains and their rapid spread across the globe, the use of both natural and synthetic AMPs and their combination with conventional drugs ( 18 , 19 ) are enabling the creation of a new generation of truly promising antibiotics ( 20 – 23 ).…”

Neoteric advancement in TB drugs and an overview on the anti-tubercular role of peptides through computational approaches

“…These epidemiological problems shed light on the relevance of the immune system to control TB and create a public health problem among large population of human. From the last century, BCG vaccine has shown some protective efficacy in combating serious TB [2]. But the lack of protecting pulmonary infections is the poor aftermath of this therapy and has been called into the million-dollar question.…”