Comparative activities of cecropin A, melittin, and cecropin A–melittin peptide CA(1–7)M(2–9)NH2 against multidrug-resistant nosocomial isolates of Acinetobacter baumannii

Giacometti, Andrea; Cirioni, Oscar; Kamysz, Wojciech; D'Amato, Giuseppina; Silvestri, Carmela; Prete, Maria Simona Del; Łukasiak, Jerzy; Scalise, Giorgio

doi:10.1016/j.peptides.2003.08.003

Cited by 66 publications

(47 citation statements)

References 13 publications

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“…CA-M hybrid peptides have been extensively reviewed as bactericidal agents (37), and some of them have been tested on Acinetobacter (1,18,40). In the present work, the four CA-M peptides displayed very similar antimicrobial activity on A. baumannii, particularly so when activities were expressed in molar terms.…”

Section: Discussionmentioning

confidence: 63%

“…Reasonable expectations have been raised about their pharmacological exploitation as potent antibacterial agents based on (i) the wide range of pathogens susceptible to them; (ii) their extremely low rate of resistance compared with classical antibiotics, resulting from a distinctive mechanism of membrane perturbation based on stoichiometric interaction of the EAP with exposed anionic lipids; and (iii) their anti-endotoxic properties, which result from their ability to interact with lipopolysaccharide (LPS). A number of EAPs have been tested, both in vitro against different species of the genus Acinetobacter (18,39,40), including multiresistant strains (1,18,40), and in vivo on animal models of bacteremia by Acinetobacter baumannii (3,12).…”

mentioning

confidence: 99%

“…Though polymyxins share major structural features (i.e., a cationic peptide nature) and self-promoted uptake mecha-nisms with most EAPs, we earlier demonstrated that polymyxin B (PXB) and the cecropin A-melittin (CA-M) hybrid CA(1-8)M (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), an EAP, differed in the last steps of their lethal activity on A. baumannii (40), warranting exploitation of the latter against colistin-resistant strains. Similar pioneering work by Urban et al established the activity of the EAPs rBPI 21 (the recombinant 21-kDa amino-terminal fragment of the bactericidal/permeability-increasing protein) and cecropin P 1 on a single polymyxin B-resistant A. baumannii isolate (43).…”

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confidence: 99%

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Activity of Cecropin A-Melittin Hybrid Peptides against Colistin-Resistant Clinical Strains of Acinetobacter baumannii : Molecular Basis for the Differential Mechanisms of Action

Saugar

Rodríguez-Hernández

Torre

et al. 2006

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 63%

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confidence: 99%

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confidence: 99%

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Activity of Cecropin A-Melittin Hybrid Peptides against Colistin-Resistant Clinical Strains of Acinetobacter baumannii : Molecular Basis for the Differential Mechanisms of Action

Saugar

Rodríguez-Hernández

Torre

et al. 2006

Antimicrob Agents Chemother

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“…Due to the fact that AMPs exploit fundamental conserved features of the bacterial cell wall, they are able to act against a broad spectrum of pathogens, including Salmonella enterica, E. coli, K. pneumoniae, P. aeruginosa, and Listeria monocytogenes (58,68,69). Also, because of the mechanism of action of AMPs, the incidence of bacterial resistance is very low.…”

Section: Discussionmentioning

confidence: 99%

Insect-Derived Cecropins Display Activity against Acinetobacter baumannii in a Whole-Animal High-Throughput Caenorhabditis elegans Model

Jayamani

Rajaraman

Larkins-Ford

et al. 2015

Antimicrob Agents Chemother

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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.A cinetobacter baumannii is a Gram-negative, opportunistic bacterium that has recently emerged as a dangerous nosocomial pathogen (1-4). An increasing number of A. baumannii infections in patients have been detected among U.S. military service members injured in Iraq and Afghanistan (5). The genetic adaptability of A. baumannii allows it to gain resistance to a wide spectrum of commercial antibiotics, and the intrinsic presence of various efflux pumps in A. baumannii also contributes to an insensitivity to many antibiotics (6-8), resulting in very few viable treatment options for Acinetobacter infections (9-11). In addition, most of the clinical strains of A. baumannii also harbor a large antimicrobial resistance island (RI) of 86 kb that contains several beta-lactamase genes, conferring resistance to beta-lactam antibiotics (12, 13). The scarcity of antibiotics that can be used against A. baumannii infections drives the need for new kinds of antimicrobial agents (14).Empirical drug screening methods traditionally involve in vitro assays to measure the MICs for various pathogens. This is followed by in vivo testing of the drugs to measure their toxicity to eukaryotic cells (15). The disadvantage of these traditional assays is that a significant number of hit compounds show nonspecific toxicity to eukaryotic cells and are not promising as therapeutics (16). In this paper, we describ...

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“…This mechanistic difference is clinically attractive and is well illustrated by the susceptibility of polymyxin-resistant A. baumannii strains to such peptides (480,562). Bactericidal activity against A. baumannii, using both in vitro (4,193,448,479,480,562) and in vivo (56, 125) models, has been reported. Combination studies, as determined by fractional inhibitory indexes, demonstrated that magainin II acted synergistically with ␤-lactams against multidrug-resistant A. baumannii but that four other peptides showed no synergy (192).…”

Section: Vol 21 2008mentioning

confidence: 99%

Acinetobacter baumannii : Emergence of a Successful Pathogen

2008

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SUMMARY Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

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Comparative activities of cecropin A, melittin, and cecropin A–melittin peptide CA(1–7)M(2–9)NH2 against multidrug-resistant nosocomial isolates of Acinetobacter baumannii

Cited by 66 publications

References 13 publications

Activity of Cecropin A-Melittin Hybrid Peptides against Colistin-Resistant Clinical Strains of Acinetobacter baumannii : Molecular Basis for the Differential Mechanisms of Action

Activity of Cecropin A-Melittin Hybrid Peptides against Colistin-Resistant Clinical Strains of Acinetobacter baumannii : Molecular Basis for the Differential Mechanisms of Action

Insect-Derived Cecropins Display Activity against Acinetobacter baumannii in a Whole-Animal High-Throughput Caenorhabditis elegans Model

Acinetobacter baumannii : Emergence of a Successful Pathogen

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