TY - JOUR
T1 - A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy
AU - Rao, Komal Umashankar
AU - Henderson, Domhnall Iain
AU - Krishnan, Nitya
AU - Puthia, Manoj
AU - Glegola-Madejska, Izabela
AU - Brive, Lena
AU - Bjarnemark, Fanny
AU - Millqvist Fureby, Anna
AU - Hjort, Karin
AU - Andersson, Dan I.
AU - Tenland, Erik
AU - Sturegård, Erik
AU - Robertson, Brian D.
AU - Godaly, Gabriela
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-83755-3
DO - 10.1038/s41598-021-83755-3
M3 - Article
C2 - 33603037
AN - SCOPUS:85101252476
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 4201
ER -