Tissue damage alleviation and mucin inhibition by P5 in a respiratory infection mouse model with multidrug-resistant
Jun Hee Oh1, Jonggwan Park2, Hee Kyoung Kang1
1Department of Integrative Biological Sciences, Chosun University Gwangju 61452, Republic of Korea.
Abstract:
Although the discovery of antibiotics has made significant positive contributions to public health and medicine, it now poses a serious threat due to the increasing antibiotic resistance in various bacteria. Carbapenem-resistant and multidrug-resistant (MDR) Acinetobacter baumannii is spreading globally, exacerbating respiratory diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Antimicrobial peptides (AMPs), with broad antibacterial activity, have emerged as promising alternatives for treating MDR A. baumannii infections. The AMP P5 exhibits strong antibacterial and anti-biofilm activities against MDR A. baumannii strains isolated from patients. Compared to colistin, a commonly used antibiotic for MDR A. baumannii infections, P5 has a lower potential for inducing drug resistance. Additionally, P5 displays stability in human serum and minimal cytotoxicity in human cell lines. P5 not only suppressed the overexpression of pro-inflammatory cytokines and inflammatory transcription factors in lung epithelial cells (A549) and in a mouse model of respiratory infection but also alleviated lung tissue damage caused by infection. Moreover, P5 effectively alleviated excessive mucin secretion in vitro and in vivo by inhibiting inflammatory transcription factors, epidermal growth factor receptor, and signal transducer and activator of transcription 3-key regulators of mucin expression, a hallmark of inflammatory respiratory diseases. These findings highlight the therapeutic potential of P5 in treating MDR A. baumannii infections and associated inflammatory respiratory conditions.
Insights
Antimicrobial peptide P5 effectively combats multidrug-resistant Acinetobacter baumannii infections and reduces inflammation in respiratory diseases. P5 shows lower resistance potential and minimal toxicity compared to colistin.
Area of Science:
- Microbiology
- Pharmacology
- Immunology
Background:
- Antibiotic resistance, particularly in multidrug-resistant (MDR) Acinetobacter baumannii, is a growing global health concern.
- MDR A. baumannii exacerbates respiratory conditions like COPD and cystic fibrosis.
- Antimicrobial peptides (AMPs) are emerging as potential alternatives to conventional antibiotics.
Purpose of the Study:
- To evaluate the therapeutic potential of the AMP P5 against MDR A. baumannii.
- To assess P5's efficacy in treating associated inflammatory respiratory diseases.
- To compare P5's safety and resistance profile with colistin.
Main Methods:
- In vitro and in vivo testing of P5 against MDR A. baumannii strains.
- Assessment of P5's antibacterial and anti-biofilm activities.
- Evaluation of P5's effects on inflammatory markers, lung tissue damage, and mucin secretion in cell lines and a mouse model.
- Cytotoxicity and serum stability assays.
Main Results:
- P5 demonstrated potent antibacterial and anti-biofilm activity against MDR A. baumannii.
- P5 showed a lower potential for inducing resistance compared to colistin.
- P5 reduced pro-inflammatory cytokine and transcription factor overexpression, alleviated lung tissue damage, and inhibited excessive mucin secretion.
- P5 exhibited stability in human serum and minimal cytotoxicity.
Conclusions:
- P5 is a promising therapeutic agent for MDR A. baumannii infections.
- P5 effectively mitigates inflammation and excessive mucin secretion in respiratory diseases associated with MDR A. baumannii.
- P5 offers a safer and potentially more effective alternative to colistin for treating these infections.
