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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Antimicrob+Agents+Chemother
2015 ; 59
(3
): 1728-37
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English Wikipedia
Insect-derived cecropins display activity against Acinetobacter baumannii in a
whole-animal high-throughput Caenorhabditis elegans model
#MMPMID25583713
Jayamani E
; Rajamuthiah R
; Larkins-Ford J
; Fuchs BB
; Conery AL
; Vilcinskas A
; Ausubel FM
; Mylonakis E
Antimicrob Agents Chemother
2015[Mar]; 59
(3
): 1728-37
PMID25583713
show ga
The rise of multidrug-resistant Acinetobacter baumannii and a concomitant
decrease in antibiotic treatment options warrants a search for new classes of
antibacterial agents. We have found that A. baumannii is pathogenic and lethal to
the model host organism Caenorhabditis elegans and have exploited this phenomenon
to develop an automated, high-throughput, high-content screening assay in liquid
culture that can be used to identify novel antibiotics effective against A.
baumannii. The screening assay involves coincubating C. elegans with A. baumannii
in 384-well plates containing potential antibacterial compounds. At the end of
the incubation period, worms are stained with a dye that stains only dead
animals, and images are acquired using automated microscopy and then analyzed
using an automated image analysis program. This robust assay yields a Z' factor
consistently greater than 0.7. In a pilot experiment to test the efficacy of the
assay, we screened a small custom library of synthetic antimicrobial peptides
(AMPs) that were synthesized using publicly available sequence data and/or
transcriptomic data from immune-challenged insects. We identified cecropin A and
14 other cecropin or cecropin-like peptides that were able to enhance C. elegans
survival in the presence of A. baumannii. Interestingly, one particular hit,
BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti,
showed antibiotic activity against a panel of Gram-negative bacteria and
exhibited a low MIC (5 ?g/ml) against A. baumannii. BR003-cecropin A causes
membrane permeability in A. baumannii, which could be the underlying mechanism of
its lethality.