Effects of the combination of anti-PcrV antibody and bacteriophage therapy in a mouse model of Pseudomonas aeruginosa pneumonia
Year: 2024
Type: article
Abstract: ABSTRACT Acute lung injury caused by Pseudomonas aeruginosa is attributed to the translocation of cytotoxin into pulmonary epithelial cells via the P. aeruginosa type III secretion system. This virulence can be blocked with a specific antibody against PcrV in this secretion system. However, because anti-PcrV antibodies do not have bactericidal activity, the treatment of bacteria depends on the phagocytic system of the host. In this study, we investigated the therapeutic effect of combination therapy with an anti-PcrV antibody and bactericidal bacteriophages on acute lung injury and subsequent death in mice compared with a single treatment. After the mice intratracheally received a lethal dose of the cytotoxic P. aeruginosa strain, a second instillation was performed with saline, anti-PcrV IgG, bacteriophages, or a mixture of anti-PcrV and bacteriophages. The survival rates 24 h after infection were as follows: 7.1% in the saline group, 26.7% in the anti-PcrV group, 41.2% in the phage group, and 66.7% in the anti-PcrV + phage group ( P < 0.001 vs saline-treated group). The activity of surviving mice in the anti-PcrV + phage group was significantly greater than that in the saline group. The lung weight in the anti-PcrV + phage group was significantly lower than that in the anti-PcrV group. In conclusion, combination therapy with an anti-PcrV antibody and a bacteriophage reduces acute lung injury and suggests improved survival compared with each treatment alone. This combination therapy, which does not rely on conventional antibiotics, could constitute a new strategy for treating multidrug-resistant P. aeruginosa infections. IMPORTANCE Combination therapy with either bacteriophages alone or in combination with anti-PcrV antibodies in a mouse model of Pseudomonas aeruginosa pneumonia may reduce the acute lung injury and improve survival. This combination therapy, which does not rely on conventional antibiotics, may be a new strategy to treat multidrug-resistant Pseudomonas aeruginosa infections.
Source: Microbiology Spectrum
Language: English
Subfield: Ecology
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Study for ELF/cytokine ratio and therapeutic effect of immunosuppressants in ARDS and COVID-19 patients, Construction of innovative phage therapy through evolutionary trade-offs, PD-L1阻害薬の治療成績向上を目指した腸内細菌叢制御を介するファージ療法の確立, G2260108729, Development of specific high-titer immunoglobulin for new coronavirus infections, Single-domian antibody against the virulence associated with the type III secretion system of gram-negative bacteria, G3768973757, Development of spike protein CpG-ODN nasal vaccine against COVID-19, An epidemiological investigation of serum titers of anti-Pseudomonas aeruginosa virulent antigens and a trial of a specific anti-Pseuomonal gamma-globulin product, Development and clinical application of next-generation phage therapy, G5316758738, Construction of a strategic phage library to overcome bacterial anti-phage defense systems, G5689513100, G6165777619, Preclinical study of Pseudomonas aeruginosa PcrV-CpG(K3)-SPG Vaccine, 見えないものの価値の認識を促すプログラミング教材の開発, G6417872798, A strategy for practical application of a next-generation, high-value-added vaccine for new SARS-CoV-2 based on mucociliary administration technology, G7333672397, Epidemiological study of serum titers against V-antigens of gram-negative bacteria, G7681308522, G817290567
OpenAlex ID: W4403685324