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Sci Rep ; 11(1): 4201, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603037

RESUMO

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Tuberculose/tratamento farmacológico , Animais , Etambutol/farmacologia , Feminino , Humanos , Isoniazida/farmacologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/métodos , Infecções por Mycobacterium não Tuberculosas/dietoterapia , Mycobacterium tuberculosis/efeitos dos fármacos , Micobactérias não Tuberculosas/efeitos dos fármacos , Rifampina/farmacologia , Tuberculose/microbiologia
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