Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002.

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis. P. aeruginosa lung infections are difficult to treat due to bacterial resistance to antibiotics, and strains with multidrug resistance are becoming more prevalent. Here, we examined the use of a small host defense peptide, innate defense regulator 1002 (IDR-1002), in an acute P. aeruginosa lung infection in vivo IDR-1002 significantly reduced the bacterial burden in bronchoalveolar lavage fluid (BALF), as well as MCP-1 in BALF and serum, KC in serum, and interleukin 6 (IL-6) in BALF. Transcriptome sequencing (RNA-Seq) was conducted on lungs and whole blood, and the effects of P. aeruginosa, IDR-1002, and the combination of P. aeruginosa and IDR-1002 were evaluated. Differential gene expression analysis showed that P. aeruginosa increased multiple inflammatory and innate immune pathways, as well as affected hemostasis, matrix metalloproteinases, collagen biosynthesis, and various metabolism pathways in the lungs and/or blood. Infected mice treated with IDR-1002 had significant changes in gene expression compared to untreated infected mice, with fewer differentially expressed genes associated with the inflammatory and innate immune responses to microbial infection, and treatment also affected morphogenesis, certain metabolic pathways, and lymphocyte activation. Overall, these results showed that IDR-1002 was effective in treating P. aeruginosa acute lung infections and associated inflammation.

• Authors: Kelli Wuerth, Amy H Y Lee, Reza Falsafi, Erin E Gill, Robert E W Hancock
• Journal: Infection and immunity (Infect Immun) Vol. 87 Issue 1 (01 2019) ISSN: 1098-5522 [Electronic] United States
• PMID: 30323028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Wuerth et al.

Chemical References

• Antimicrobial Cationic Peptides
• Ccl2 protein, mouse
• Chemokine CCL2
• IDR 1002

Topics

• Animals
• Antimicrobial Cationic Peptides (administration & dosage)
• Bacteremia (drug therapy, pathology)
• Bacterial Load
• Bronchoalveolar Lavage Fluid (chemistry, microbiology)
• Chemokine CCL2 (analysis)
• Disease Models, Animal
• Female
• Gene Expression Profiling
• Mice, Inbred C57BL
• Pneumonia (drug therapy, pathology)
• Pseudomonas Infections (drug therapy, pathology)
• Pseudomonas aeruginosa (isolation & purification)
• Serum (chemistry, microbiology)
• Treatment Outcome