In vitro and invivo characterization of a new recombinant antimicrobial peptide, MP1102, against methicillin-resistant Staphylococcus aureus

Verfasser / Beitragende:
[Yong Zhang, Da Teng, Xiumin Wang, Ruoyu Mao, Xintao Cao, Xiaoyuan Hu, Lifen Zong, Jianhua Wang]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/15(2015-08-01), 6255-6266
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6394-7  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6394-7 
245 0 0 |a In vitro and invivo characterization of a new recombinant antimicrobial peptide, MP1102, against methicillin-resistant Staphylococcus aureus  |h [Elektronische Daten]  |c [Yong Zhang, Da Teng, Xiumin Wang, Ruoyu Mao, Xintao Cao, Xiaoyuan Hu, Lifen Zong, Jianhua Wang] 
520 3 |a Currently, more antimicrobial drug candidates are urgently needed to combat the rise in drug-resistance among pathogenic microbes. A new antimicrobial peptide, MP1102, a variant of NZ2114, was designed, evaluated, and overexpressed in Pichia pastoris. The total secreted protein in cultures reached 695mg/l, and the concentration of the recombinant MP1102 (rMP1102) was 292mg/l. rMP1102 was purified from the fermentation supernatant by one-step cation exchange chromatography to obtain a yield of 197.1mg/l with 96.4% purity. rMP1102 exhibited potent activity against Gram-positive bacteria, and its minimum inhibitory concentrations (MICs) for four Staphyloccocus aureus (S. aureus) strains ranged from 0.028 to 0.11μM, and it had stronger activity (MIC = 0.04 to 0.23μM) to 20 clinical isolates of MRSA (cMRSA) than rNZ2114 (MIC = 0.11 to 0.90μM). rMP1102 was shown to kill over 99.9% of tested S. aureus cells within 6h when treated at one, two, and four times its MIC and over 90% of S. aureus cells within 12h at concentrations of 5, 10, and 20mg/kg in a mouse thigh infection model. The higher sensitivity of MRSA to MP1102 than to its parental peptide, NZ2114, indicated by this initial pharmacodynamic analysis suggests a possible difference in the killing mechanism of these two molecules. rMP1102 caused less than 0.05% hemolytic activity at 128μg/ml and exhibited good thermostability from 20 to 80°C, with its highest activity being observed at pH8.0. These results suggest that this yeast expression system is feasible for large-scale production, and rMP1102 exerted stronger activity against S. aureus than NZ2114 via a different mechanism and exhibited potential as a new antimicrobial agent for S. aureus, especially MRSA infections. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Molecular design  |2 nationallicence 
690 7 |a MP1102  |2 nationallicence 
690 7 |a Pichia pastoris  |2 nationallicence 
690 7 |a MRSA  |2 nationallicence 
690 7 |a Antimicrobial peptides  |2 nationallicence 
700 1 |a Zhang  |D Yong  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Teng  |D Da  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Wang  |D Xiumin  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Mao  |D Ruoyu  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Cao  |D Xintao  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Hu  |D Xiaoyuan  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Zong  |D Lifen  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
700 1 |a Wang  |D Jianhua  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/15(2015-08-01), 6255-6266  |x 0175-7598  |q 99:15<6255  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6394-7  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6394-7  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Yong  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Teng  |D Da  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Xiumin  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Mao  |D Ruoyu  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Cao  |D Xintao  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hu  |D Xiaoyuan  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zong  |D Lifen  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Jianhua  |u Key Laboratory of Feed Biotechnology, Ministry of Agriculture, 100081, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/15(2015-08-01), 6255-6266  |x 0175-7598  |q 99:15<6255  |1 2015  |2 99  |o 253