In vitro and invivo characterization of a new recombinant antimicrobial peptide, MP1102, against methicillin-resistant Staphylococcus aureus
Gespeichert in:
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)
Online Zugang:
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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 |
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| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
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| 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 | ||