Evaluation of Phage Therapy for Pulmonary Infection of Mouse by Liquid Aerosol-Exposure Pseudomonas aeruginosa

Abstract

Background: Pseudomonas aeruginosa is an important nosocomial infectious bacterium, more and more multidrug resistant P. aeruginosa have been isolated and posed severe challenges to clinical antibiotic treatment, bringing additional morbidity, mortality, and economic burden. Bacteriophages can lyse bacteria specificity and are feasible alternatives to antibiotics. Methods: A Pseudomonas aeruginosa-infecting phage vB_PaeP_PA01EW was isolated. Phage plaque assays, transmission electron microscopy, host-range determination, infection assay analyses, whole-genome sequencing and annotation were performed for the phage. Mice pneumonia model using liquid aerosol-exposure Pseudomonas aeruginosa was established, and phage therapy was evaluated. Results: vB_PaeP_PA01EW belongs to the family Podoviridae according to transmission electron microscopy and was identified as a Luz24likevirus according to the genome analysis. For the phage therapy, compared with the bacteria-infected group, the phage-rescue group has some characteristics. First, adventitial edema and diffuse infiltration of inflammatory cells in tissues were alleviated, Second, bronchial epithelial cell proliferation was reduced. Third, the bacterial burden was significantly decreased. Conclusion:This study provided data support and theoretical basis for the clinical application of bacteriophages. It has important guiding significance and reference value for the application of bacteriophage therapy of other pathogenic bacteria.

Administration of Bacteriophages via Nebulization during Mechanical Ventilation: In Vitro Study and Lung Deposition in Macaques

“…In contrast, Podoviridae seem to be more affected by the 45 °C temperature. These data agreed with [ 44 ], who found the same viability loss after a 15 min exposition at 50 °C (−1 log PFU) and at 60 °C (−2 logPFU/mL). In conclusion, it is unlikely that viability loss by tail breakage of Myoviridae would be due to high temperature.…”

“…We have shown that these parameters have no significant impact on phage viability, whatever the phage family ( Figure 5 c). This result was also described by Zhang et al (2021) for a 37 °C biological temperature [ 44 ].…”

“…To ensure a robust interpretation of the TEM images, the phages were ultra-centrifuged before nebulization to remove initial structural damage and, thus, to visualize only those attributable to the nebulization process. As previously observed [ 44 ], Podoviridae presented an intact structure, while numerous detached tails were present in the Myoviridae samples. As confirmed by other studies, Myoviridae can easily lose activity by tail detachment [ 22 ].…”

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

“…The therapeutic potential of bacteriophages targeting MDR strains of GNB using animal models was evaluated in vitro and showed high infectivity of phages and multiple phage doses were required for effective treatment in vivo [ 113 ]. Novel treatment options such as PlyF307 lysine phage against MDR A. baumannii , VTCCBPA43 phage against virulent K. pneumoniae , PlyPa91 and vB_PaeP_PA01EW phages against P. aeruginosa , and Abp95 lytic myoviridae phage against multi-genotypes of carbapenem-resistant A. baumannii were demonstrated in mouse models [ 114 – 118 ]. Tridecaptins, a non-ribosomal lipopeptide, showed a selective bactericidal activity against the gram-negative version of the peptidoglycan precursor lipid II on the outer leaflet of the inner membrane and disrupts the proton-motive force [ 119 ].…”

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study

“…Hua et al (2017) and Kvachadze et al (2011) reported that in clinical trials, no side effects were observed during the treatment of pulmonary infections by bacteriophage nebulization [ 34 , 35 ]. Yajun et al (2021) evaluated phage therapy for a lung infection in mice by liquid aerosol-exposure Pseudomonas aeruginosa [ 36 ]. The authors reported no obvious alterations in the lung tissue of the phage group in comparison to the control group.…”