Lactoferricin peptides increase macrophages' capacity to kill mycobacterium avium

T. Silva, A.C. Moreira, K. Nazmi, T. Moniz, N. Vale, M. Rangel, P. Gomes, J.G.M. Bolscher, P.N. Rodrigues, M. Bastos, M.S. Gomes

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17–30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture. In the present work, those peptides were tested against M. avium living inside its natural host cell, the macrophage. We found that the peptides increased the antimicrobial action of the conventional antibiotic ethambutol inside macrophages. Moreover, the d-enantiomer of the lactoferricin peptide (d-LFcin17–30) was more stable and induced significant killing of intracellular mycobacteria by itself. Interestingly, d-LFcin17–30 did not localize to M. avium-harboring phagosomes but induced the production of proinflammatory cytokines and increased the formation of lysosomes and autophagosome-like vesicles. These results lead us to conclude that d-LFcin17–30 primes macrophages for intracellular microbial digestion through phagosomal maturation and/or autophagy, culminating in mycobacterial killing.
Original languageEnglish
Article numbere0030-17
Number of pages14
JournalmSphere
Volume2
Issue number4
DOIs
Publication statusPublished - 2017

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