A Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureus.
A Defensin from the Model Beetle Tribolium castaneum Acts Synergistically with Telavancin and Daptomycin against Multidrug Resistant Staphylococcus aureus.
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DOI：
10.1371/journal.pone.0128576
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Mylonakis E
中科院分区：
文献类型：
--
作者：
Rajamuthiah R;Jayamani E;Conery AL;Fuchs BB;Kim W;Johnston T;Vilcinskas A;Ausubel FM;Mylonakis E
The red flour beetle Tribolium castaneum is a common insect pest and has been established as a model beetle to study insect development and immunity. This study demonstrates that defensin 1 from T. castaneum displays in vitro and in vivo antimicrobial activity against drug resistant Staphylococcus aureus strains. The minimum inhibitory concentration (MIC) of defensin 1 against 11 reference and clinical staphylococcal isolates was between 16–64 μg/ml. The putative mode of action of the defensin peptide is disruption of the bacterial cell membrane. The antibacterial activity of defensin 1 was attenuated by salt concentrations of 1.56 mM and 25 mM for NaCl and CaCl2 respectively. Treatment of defensin 1 with the reducing agent dithiothreitol (DTT) at concentrations 1.56 to 3.13 mM abolished the antimicrobial activity of the peptide. In the presence of subinhibitory concentrations of antibiotics that also target the bacterial cell envelope such as telavancin and daptomycin, the MIC of the peptide was as low as 1 μg/ml. Moreover, when tested against an S. aureus strain that was defective in D-alanylation of the cell wall, the MIC of the peptide was 0.5 μg/ml. Defensin 1 exhibited no toxicity against human erythrocytes even at 400 μg/ml. The in vivo activity of the peptide was validated in a Caenorhabditis elegans-MRSA liquid infection assay. These results suggest that defensin 1 behaves similarly to other cationic AMPs in its mode of action against S. aureus and that the activity of the peptide can be enhanced in combination with other antibiotics with similar modes of action or with compounds that have the ability to decrease D-alanylation of the bacterial cell wall.
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影响因子：
4.9
作者：
Eckert, R;Qi, FX;Shi, WY
通讯作者：
Shi, WY
影响因子：
3.7
作者：
Rajamuthiah R;Fuchs BB;Jayamani E;Kim Y;Larkins-Ford J;Conery A;Ausubel FM;Mylonakis E
通讯作者：
Mylonakis E
影响因子：
3.1
作者：
MACK, D;NEDELMANN, M;LAUFS, R
通讯作者：
LAUFS, R
DOI：
10.1073/pnas.1404099111
发表时间：
2014-08-26
影响因子：
11.1
作者：
Maria, John P. Santa, Jr.;Sadaka, Ama;Walker, Suzanne
通讯作者：
Walker, Suzanne
影响因子：
3.1
作者：
Sifri, CD;Begun, J;Calderwood, SB
通讯作者：
Calderwood, SB