<p>Potential role of the antimicrobial peptide <em>Tachyplesin III</em> against multidrug-resistant <em>P. aeruginosa</em> and <em>A. baumannii</em> coinfection in an animal model</p>

Abstract

BackgroundTachyplesin III, an antimicrobial peptide (AMP), provides protection against multidrug-resistant (MDR) bacterial infections and shows cytotoxicity to mammalian cells. Mixed bacterial infections, of which P. aeruginosa plus A. baumannii is the most common and dangerous combination, are critical contributors to the morbidity and mortality of long-term in-hospital respiratory medicine patients. Therefore, the development of effective therapeutic approaches to mixed bacterial infections is urgently needed.Methods and resultsIn this study, we demonstrated that compared with individual infections, mixed infections with MDR bacteria P. aeruginosa and A. baumannii cause more serious diseases, with increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokines (MCP-1/MIP-2) and reduced mouse survival. In vitro treatment with Tachyplesin III enhanced phagocytosis in a mouse alveolar macrophage cell line (MH-S). Strikingly, in vivo, Tachyplesin III demonstrated a potential role against mixed-MDR bacterial coinfection. The bacterial burden in bronchoalveolar lavage fluid (BALF) was significantly reduced in the Tachyplesin III-treated group. In addition, a systemic reduction in pro-inflammatory cytokines and decreased lung injury occurred with Tachyplesin III therapy.ConclusionTherefore, our study demonstrated that Tachyplesin III represents a potential therapeutic treatment against mixed-MDR bacterial infection in vivo, which sheds light on the development of therapeutic strategies against mixed-MDR bacterial infections.

Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections

“…The peptide enhances the phagocytic function in mouse alveolar macrophages when tested in vitro, which hints at its candidacy as a clinical drug for the treatment of respiratory tract and lung infections. 94 Murepavadin (POL7080) is peptidomimetic based on the cationic AMP protegrin 1. It has passed the phase 2 clinical trials for the treatment of ventilator-associated bacterial pneumonia caused by P. aeruginosa (NCT02096328).…”

“…Moreover, Tachyplesin III can also decrease the levels of pro‐inflammatory cytokines in the serum, including IL‐1β, IL‐6, and TNF‐α. The peptide enhances the phagocytic function in mouse alveolar macrophages when tested in vitro, which hints at its candidacy as a clinical drug for the treatment of respiratory tract and lung infections 94 . Murepavadin (POL7080) is peptidomimetic based on the cationic AMP protegrin 1.…”

Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting

“…There is speculation that the secondary and tertiary structures of these molecules determine their lethality, but interestingly, the two AMPs noted differ in both secondary structure and hydrophilic/hydrophobic arrangements [50]. An in vivo study examining tachyplesin III's role in combating concomitant P. aeruginosa and A. baumannii lung infections found that pre-treatment with the peptide reduced inflammation, bacterial burden, and lung damage by increasing phagocytosis and reducing cytokine release in mice [51]. If funding can be secured, AMPs may be the future of antimicrobial treatment strategies.…”

Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections

“…Only a few AMPs have been tested in lung polymicrobial infections. One of these peptides is the Tachyplesin III, a β-sheet peptide from the hemocytes of the horseshoe crab ( Tachypleus tridentatus ), which has been tested in bacterial co-infection pneumonia [ 55 ]. As compared to mono-bacterial infection, the intranasal co-infection of mice with MDR P. aeruginosa and A. baumannii caused a more serious disease, with increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokines (MCP-1/MIP-2) and reduced survival.…”