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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.

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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.
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Figure 1: 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.

Mentions: We determined the growth rates of S. aureus strain 8325-4 and MRSA strain USA300 in MHB-II medium at 29°C because all successive in vivo experiments were performed at this temperature. Strain 8325-4 had a generation time of 57 min, while USA300 had a generation time of 44 min (data not shown). The in vivo growth rates of the same strains were determined by injection of bacteria into flies at time zero, with samples collected at time zero and at 3, 4 to 6, and 12 h postinfection. USA300 had a generation time of 54 min, whereas 8325-4 had a generation time of 104 min in vivo (Fig. 1A). Drosophila flies infected with USA300 died rapidly, with no surviving flies at 24 h postinfection (Fig. 1B). Flies infected with approximately the same number of 8325-4 organisms lived significantly longer. We suggest that this difference in viability reflects the difference in in vivo growth rates of USA300 and 8325-4 bacteria.


The Lantibiotic NAI-107 Efficiently Rescues Drosophila melanogaster from Infection with Methicillin-Resistant Staphylococcus aureus USA300
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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: 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.
Mentions: We determined the growth rates of S. aureus strain 8325-4 and MRSA strain USA300 in MHB-II medium at 29°C because all successive in vivo experiments were performed at this temperature. Strain 8325-4 had a generation time of 57 min, while USA300 had a generation time of 44 min (data not shown). The in vivo growth rates of the same strains were determined by injection of bacteria into flies at time zero, with samples collected at time zero and at 3, 4 to 6, and 12 h postinfection. USA300 had a generation time of 54 min, whereas 8325-4 had a generation time of 104 min in vivo (Fig. 1A). Drosophila flies infected with USA300 died rapidly, with no surviving flies at 24 h postinfection (Fig. 1B). Flies infected with approximately the same number of 8325-4 organisms lived significantly longer. We suggest that this difference in viability reflects the difference in in vivo growth rates of USA300 and 8325-4 bacteria.

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.


Related in: MedlinePlus