Antimicrobial efficacy and toxicity of novel CAMPs against P. aeruginosa infection in a murine skin wound infection model

Ming Yang; Chunye Zhang; Sarah A Hansen; William J Mitchell; Michael Z Zhang; Shuping Zhang

doi:10.1186/s12866-019-1657-6

Antimicrobial efficacy and toxicity of novel CAMPs against P. aeruginosa infection in a murine skin wound infection model

BMC Microbiol. 2019 Dec 16;19(1):293. doi: 10.1186/s12866-019-1657-6.

Authors

Ming Yang¹, Chunye Zhang¹, Sarah A Hansen², William J Mitchell^{1

3}, Michael Z Zhang^{3

4}, Shuping Zhang^{5

6}

Affiliations

¹ Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
² Office of Animal Resources, University of Missouri, Columbia, MO, 65211, USA.
³ Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
⁴ Department of Biomedical Science, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
⁵ Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA. zhangshup@missouri.edu.
⁶ Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA. zhangshup@missouri.edu.

Abstract

Background: Treatment of P. aeruginosa wound infection is challenging due to its inherent and acquired resistance to many conventional antibiotics. Cationic antimicrobial peptides (CAMPs) with distinct modes of antimicrobial action have been considered as the next-generation therapeutic agents. In the present study, a murine skin surgical wound infection model was used to evaluate the in vivo toxicity and efficacy of two newly designed antimicrobial peptides (CAMP-A and CAMP-B), as chemotherapeutic agents to combat P. aeruginosa infection.

Results: In the first trial, topical application of CAMPs on the wounds at a dose equivalent to 4 × MIC for 7 consecutive days did not cause any significant changes in the physical activities, hematologic and plasma biochemical parameters, or histology of systemic organs of the treated mice. Daily treatment of infected wounds with CAMP-A and CAMP-B for 5 days at a dose equivalent to 2× MIC resulted in a significant reduction in wound bacterial burden (CAMP-A: 4.3 log₁₀CFU/g of tissue and CAMP-B: 5.8 log₁₀CFU/g of tissue), compared to that of the mock-treated group (8.1 log₁₀CFU/g of tissue). Treatment with CAMPs significantly promoted wound closure and induced epidermal cell proliferation. Topical application of CAMP-A on wounds completely prevented systemic dissemination of P. aeruginosa while CAMP-B blocked systemic infection in 67% of mice and delayed the onset of systemic infection by at least 2 days in the rest of the mice (33%). In a second trial, daily application of CAMP-A at higher doses (5× MIC and 50× MIC) didn't show any significant toxic effect on mice and the treatments with CAMP-A further reduced wound bacterial burden (5× MIC: 4.5 log₁₀CFU/g of tissue and 50× MIC: 3.8 log₁₀CFU/g of tissue).

Conclusions: The data collectively indicated that CAMPs significantly reduced wound bacterial load, promoted wound healing, and prevented hepatic dissemination. CAMP-A is a promising alternative to commonly used antibiotics to treat P. aeruginosa skin infection.

Keywords: Antimicrobial activity; Cationic antimicrobial peptides; Mouse model; Pseudomonas aeruginosa; Skin infection; Toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Topical
Animals
Antimicrobial Cationic Peptides / therapeutic use*
Bacterial Load
Disease Models, Animal
Female
Mice
Mice, Inbred BALB C
Pseudomonas Infections / microbiology
Pseudomonas Infections / therapy*
Pseudomonas aeruginosa
Skin / microbiology*
Skin / pathology
Surgical Wound Infection / microbiology
Surgical Wound Infection / therapy
Wound Healing
Wound Infection / microbiology
Wound Infection / therapy*

Substances

Antimicrobial Cationic Peptides