Effects of intratracheal administration of novispirin G10 on a rat model of mucoid Pseudomonas aeruginosa lung infection.
Chronic Pseudomonas aeruginosa lung infection is a major problem for patients with cystic fibrosis (CF). The biofilm mode of growth of the pathogen makes it highly resistant to antibiotic treatment, and this is especially pronounced with mucoid strains. In this study, novispirin G10, a synthetic antimicrobial peptide patterned loosely on sheep myeloid antimicrobial peptide 29, was tested in a rat model of mucoid P. aeruginosa lung infection. P. aeruginosa NH57388A, a mucoid strain isolated from a CF patient, was mixed with the alginate produced by the bacterium itself and adjusted to a concentration of 10(10) CFU/ml. Each rat received 10(9) CFU of bacteria intratracheally in the left lung to establish lung infection. At 0 and 3 h post P. aeruginosa infection, the treated group of rats received novispirin G10 (0.1 mg/ml, 0.1 ml/rat) intratracheally, whereas the control group received vehicle treatment only. The animals were sacrificed on days 3, 5, 7, and 10 after challenge for evaluation of various parameters. On day 5, 50% of the rats in the treated group had cleared the bacteria from the lungs, whereas in the control group, none of the rats cleared the pathogen (P < 0.03). The average bacterial loads remaining in the lungs of treated rats on days 3 and 5 were more than 170- and 330-fold lower than in the control groups (P < 0.0005 and P < 0.0003). In accordance, the macroscopic and microscopic lung pathology was also significantly milder in the treated group compared to the control group (P < 0.0002). Lung cytokine responses in the treated group were significantly lower than in the control group. The results suggest that novispirin G10 might be useful in treating antibiotic-resistant P. aeruginosa lung infections.
Song
Zhijun
Z
Department of Clinical Microbiology, Afsnit 9301, University Hospital of Copenhagen, Rigshospitalet, Juliane Maries Vej 22, DK-2100 Copenhagen Ø, Denmark. zhijun.song@rh.dk
Wu
Hong
H
Mygind
Per
P
Raventos
Dora
D
Sonksen
Carsten
C
Kristensen
Hans-Henrik
HH
Høiby
Niels
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000096:biosynthesis / Q000627:therapeutic use*; D003001:Cloning, Molecular; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D011994:Recombinant Proteins; C466663:novispirin G10