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

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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.


Efficacies of nisin and NAI-107 in vivo against S. aureus USA300. (A) Nisin prolonged the life span of infected flies at all concentrations. (B) NAI-107 rescued 50 to 60% of flies at 100× MIC (P < 0.001), similarly to vancomycin at 10× MIC. Antibiotics were injected at 3 h postinfection (dotted line). (C) Bacterial titers in vivo in flies of the different treatment groups. Treatment with antibiotics was given at 3 h postinfection, and bacterial titers at 3 h were determined prior to treatment.
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Figure 4: Efficacies of nisin and NAI-107 in vivo against S. aureus USA300. (A) Nisin prolonged the life span of infected flies at all concentrations. (B) NAI-107 rescued 50 to 60% of flies at 100× MIC (P < 0.001), similarly to vancomycin at 10× MIC. Antibiotics were injected at 3 h postinfection (dotted line). (C) Bacterial titers in vivo in flies of the different treatment groups. Treatment with antibiotics was given at 3 h postinfection, and bacterial titers at 3 h were determined prior to treatment.

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
Efficacies of nisin and NAI-107 in vivo against S. aureus USA300. (A) Nisin prolonged the life span of infected flies at all concentrations. (B) NAI-107 rescued 50 to 60% of flies at 100× MIC (P < 0.001), similarly to vancomycin at 10× MIC. Antibiotics were injected at 3 h postinfection (dotted line). (C) Bacterial titers in vivo in flies of the different treatment groups. Treatment with antibiotics was given at 3 h postinfection, and bacterial titers at 3 h were determined prior to treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Efficacies of nisin and NAI-107 in vivo against S. aureus USA300. (A) Nisin prolonged the life span of infected flies at all concentrations. (B) NAI-107 rescued 50 to 60% of flies at 100× MIC (P < 0.001), similarly to vancomycin at 10× MIC. Antibiotics were injected at 3 h postinfection (dotted line). (C) Bacterial titers in vivo in flies of the different treatment groups. Treatment with antibiotics was given at 3 h postinfection, and bacterial titers at 3 h were determined prior to treatment.
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.