Killing of Mycobacterium avium by lactoferricin peptides: improved activity of arginine- and D-amino-acid-containing molecules.
Mycobacterium avium causes respiratory disease in susceptible individuals, as well as disseminated infections in immunocompromised hosts, being an important cause of morbidity and mortality among these populations. Current therapies consist of a combination of antibiotics taken for at least 6 months, with no more than 60% overall clinical success. Furthermore, mycobacterial antibiotic resistance is increasing worldwide, urging the need to develop novel classes of antimicrobial drugs. One potential and interesting alternative strategy is the use of antimicrobial peptides (AMP). These are present in almost all living organisms as part of their immune system, acting as a first barrier against invading pathogens. In this context, we investigated the effect of several lactoferrin-derived AMP against M. avium. Short peptide sequences from both human and bovine lactoferricins, namely, hLFcin1-11 and LFcin17-30, as well as variants obtained by specific amino acid substitutions, were evaluated. All tested peptides significantly inhibited the axenic growth of M. avium, the bovine peptides being more active than the human. Arginine residues were found to be crucial for the display of antimycobacterial activity, whereas the all-d-amino-acid analogue of the bovine sequence displayed the highest mycobactericidal activity. These findings reveal the promising potential of lactoferricins against mycobacteria, thus opening the way for further research on their development and use as a new weapon against mycobacterial infections.
IBMC (Instituto de Biologia Molecular e Celular), Universidade do Porto, Porto, Portugal CIQ(UP), Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal ICBAS (Instituto de Ciências Biomédicas Abel Salazar), Universidade do Porto, Porto, Portugal.
Tânia
T
Silva
IBMC (Instituto de Biologia Molecular e Celular), Universidade do Porto, Porto, Portugal.
Bárbara
B
Magalhães
CIQ(UP), Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
Sílvia
S
Maia
CIQ(UP), Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
Paula
P
Gomes
Department of Oral Biochemistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Kamran
K
Nazmi
Department of Oral Biochemistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
Jan G M
JG
Bolscher
IBMC (Instituto de Biologia Molecular e Celular), Universidade do Porto, Porto, Portugal ICBAS (Instituto de Ciências Biomédicas Abel Salazar), Universidade do Porto, Porto, Portugal.
Pedro N
PN
Rodrigues
CIQ(UP), Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
Margarida
M
Bastos
IBMC (Instituto de Biologia Molecular e Celular), Universidade do Porto, Porto, Portugal ICBAS (Instituto de Ciências Biomédicas Abel Salazar), Universidade do Porto, Porto, Portugal sgomes@ibmc.up.pt.
Maria Salomé
MS
Gomes
D019943:Amino Acid Substitution; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001120:Arginine; D002417:Cattle; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D009164:Mycobacterium Infections / Q000188:drug therapy* / Q000382:microbiology; D009162:Mycobacterium avium / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D010455:Peptides; C082171:lactoferricin B; D001120:Arginine; D007781:Lactoferrin