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The Lantibiotic NAI-107 Efficiently Rescues Drosophila melanogaster from Infection with Methicillin-Resistant Staphylococcus aureus USA300

View Article: PubMed Central - PubMed

ABSTRACT

We used the fruit fly Drosophila melanogaster as a cost-effective in vivo model to evaluate the efficacy of novel antibacterial peptides and peptoids for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. A panel of peptides with known antibacterial activity in vitro and/or in vivo was tested in Drosophila. Although most peptides and peptoids that were effective in vitro failed to rescue lethal effects of S. aureus infections in vivo, we found that two lantibiotics, nisin and NAI-107, rescued adult flies from fatal infections. Furthermore, NAI-107 rescued mortality of infection with the MRSA strain USA300 with an efficacy equivalent to that of vancomycin, a widely applied antibiotic for the treatment of serious MRSA infections. These results establish Drosophila as a useful model for in vivo drug evaluation of antibacterial peptides.

No MeSH data available.


In vivo efficacies of compounds against S. aureus 8325-4 in a Drosophila whole-animal model. The graphs show the effects of different peptides and peptoids on survival of flies. (A) Ampicillin; (B) NAI-107; (C) nisin; (D) GN-4; (E) GN-4 peptoid. Flies were counted at 0, 3, 6, 12, 24, and 48 to 120 h. Flies were injected with either vehicle (VEH) or isolate 8325-4 at time zero, with the indicated treatments given at 3 h (dotted lines). Flies were counted prior to injection with compound. Compound concentrations are given as approximate concentrations in animals.
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Figure 2: In vivo efficacies of compounds against S. aureus 8325-4 in a Drosophila whole-animal model. The graphs show the effects of different peptides and peptoids on survival of flies. (A) Ampicillin; (B) NAI-107; (C) nisin; (D) GN-4; (E) GN-4 peptoid. Flies were counted at 0, 3, 6, 12, 24, and 48 to 120 h. Flies were injected with either vehicle (VEH) or isolate 8325-4 at time zero, with the indicated treatments given at 3 h (dotted lines). Flies were counted prior to injection with compound. Compound concentrations are given as approximate concentrations in animals.

Mentions: In vivo growth rates and killing of flies of the two bacterial isolates. (A) The in vivo growth rate of USA300 was 54 min, and that of strain 8325-4 was 104 min, demonstrating a difference in proliferation. Three flies were homogenized and serial dilutions were made in PBS before plating on S. aureus-selective MSA to determine the number of CFU. (B) USA300 killed close to 100% of infected flies within 24 h, while isolate 8325-4 killed approximately 50% of flies within 24 h of infection (P < 0.0001). Minor differences in the starting inoculums were observed (see Materials and Methods). Survival data are compiled results from all in vivo kill rate experiments presented in Fig. 2 and 4.


The Lantibiotic NAI-107 Efficiently Rescues Drosophila melanogaster from Infection with Methicillin-Resistant Staphylococcus aureus USA300
In vivo efficacies of compounds against S. aureus 8325-4 in a Drosophila whole-animal model. The graphs show the effects of different peptides and peptoids on survival of flies. (A) Ampicillin; (B) NAI-107; (C) nisin; (D) GN-4; (E) GN-4 peptoid. Flies were counted at 0, 3, 6, 12, 24, and 48 to 120 h. Flies were injected with either vehicle (VEH) or isolate 8325-4 at time zero, with the indicated treatments given at 3 h (dotted lines). Flies were counted prior to injection with compound. Compound concentrations are given as approximate concentrations in animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997821&req=5

Figure 2: In vivo efficacies of compounds against S. aureus 8325-4 in a Drosophila whole-animal model. The graphs show the effects of different peptides and peptoids on survival of flies. (A) Ampicillin; (B) NAI-107; (C) nisin; (D) GN-4; (E) GN-4 peptoid. Flies were counted at 0, 3, 6, 12, 24, and 48 to 120 h. Flies were injected with either vehicle (VEH) or isolate 8325-4 at time zero, with the indicated treatments given at 3 h (dotted lines). Flies were counted prior to injection with compound. Compound concentrations are given as approximate concentrations in animals.
Mentions: In vivo growth rates and killing of flies of the two bacterial isolates. (A) The in vivo growth rate of USA300 was 54 min, and that of strain 8325-4 was 104 min, demonstrating a difference in proliferation. Three flies were homogenized and serial dilutions were made in PBS before plating on S. aureus-selective MSA to determine the number of CFU. (B) USA300 killed close to 100% of infected flies within 24 h, while isolate 8325-4 killed approximately 50% of flies within 24 h of infection (P < 0.0001). Minor differences in the starting inoculums were observed (see Materials and Methods). Survival data are compiled results from all in vivo kill rate experiments presented in Fig. 2 and 4.

View Article: PubMed Central - PubMed

ABSTRACT

We used the fruit fly Drosophila melanogaster as a cost-effective in vivo model to evaluate the efficacy of novel antibacterial peptides and peptoids for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. A panel of peptides with known antibacterial activity in vitro and/or in vivo was tested in Drosophila. Although most peptides and peptoids that were effective in vitro failed to rescue lethal effects of S. aureus infections in vivo, we found that two lantibiotics, nisin and NAI-107, rescued adult flies from fatal infections. Furthermore, NAI-107 rescued mortality of infection with the MRSA strain USA300 with an efficacy equivalent to that of vancomycin, a widely applied antibiotic for the treatment of serious MRSA infections. These results establish Drosophila as a useful model for in vivo drug evaluation of antibacterial peptides.

No MeSH data available.