Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas Disease

Abstract

In 2020, the WHO established the road map for neglected tropical diseases 2021–2030, which aims to control and eradicate 20 diseases, including leishmaniosis and Chagas disease. In addition, since 2015, the WHO has been developing a Global Action Plan on Antimicrobial Resistance. In this context, the achievement of innovative strategies as an alternative to replace conventional therapies is a first-order socio-sanitary priority, especially regarding endemic zoonoses in poor regions, such as those caused by Trypanosoma cruzi and Leishmania spp. infections. In this scenario, it is worth highlighting a group of natural peptide molecules (AMPs and CPPs) that are promising strategies for improving therapeutic efficacy against these neglected zoonoses, as they avoid the development of toxicity and resistance of conventional treatments. This review presents the novelties of these peptide molecules and their ability to cross a whole system of cell membranes as well as stimulate host immune defenses or even serve as vectors of molecules. The efforts of the biotechnological sector will make it possible to overcome the limitations of antimicrobial peptides through encapsulation and functionalization methods to obtain approval for these treatments to be used in clinical programs for the eradication of leishmaniosis and Chagas disease.

A novel prolixicin identified in common bed bugs with activity against both bacteria and parasites

“…CL-prolixicin not only reduced the reproduction and survival of T. cruzi , it also severely impaired its motility 51 , 52 . Antiparasitic activity of various AMPs, such as BatxC, cecropin, crotalicidin, defensin a1138, dermaseptins, and mellitin, against T. cruzi has previously been demonstrated under laboratory conditions 16 , 31 , 52 – 54 . Results obtained in laboratory experiments suggested that T. cruzi may survive in the bed bugs’ midgut but is killed if it enters the hemocoel 27 , 29 .…”

“…It has been hypothesized that some components of the bed bugs’ innate immune responses, including AMPs, prevent the establishment and replication of pathogens and their transmission to new hosts. Moreover, since 2020, the World Health Organization has assigned key roles to AMPs in the fight against neglected tropical diseases, including Chagas disease 30 , 31 .…”

The Potential Use of Peptides in the Fight against Chagas Disease and Leishmaniasis

“…Due to their direct anti-microbial killing activity and significant role in innate immunity, AMPs represent a promising alternative to existing antibiotics in the treatment and prevention of microbial infections [ 292 ]. To date, more than 2000 AMPs have been discovered, and many exhibit broad-spectrum anti-bacterial, anti-viral, and anti-parasitic activity [ 294 ]. Research on the potential application of AMPs’ structural and natural analogs in the fight against NTDs is ongoing [ 292 ].…”

“…The primary mechanism by Ih AIPs inhibit parasItic infection is by binding to and rupturing the plasma membrane of the parasites [ 294 , 295 ]. Most of these peptides are cationic–amphipathic, exhibiting two main mechanisms of action: direct lysis and modulating the immune system [ 289 ].…”

“…While AMP mechanisms remain unclear, many AMPs cause swelling in the promastigote membrane, which leads to loss of integrity and substantial cell death [ 208 ]. The development of AMPs for therapeutic applications against NTDs faces several challenges, such as natural AMP lability, susceptibility to protease, pH changes, and potential toxicity [ 289 , 294 ]. The advantages of AMPs over conventional antibiotics include a slower emergence of resistance, broad-spectrum activity, and efficacy against drug-resistant Gram-positive organisms [ 291 , 300 ].…”