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Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Isolation and characterization of two phages infecting Acinetobacter baumannii and their effectiveness in treating
Zeshan Zeshan1,2, Shafia Maryam2, Aqsa Jabeen3
1Department of Chemistry and Life Science, Yokohama National University, Yokohama, Kanagawa, Japan.
Abstract:
Acinetobacter baumannii has raised significant concern due to its high rates of morbidity and mortality, coupled with its increasing resistance to multiple antibiotics including carbapenems. In this current study, two new lytic phages Srynta and Nolivar were isolated from sewage water, characterized in vitro and their therapeutic potential was assessed using a mouse model of pneumonia. In vitro results showed that both phages show efficient adsorption to the propagating host, have good lytic activity, short latent period and high burst size. Sequence analysis showed that Srynta and Nolivar phages have linear dsDNA genomes of 45,218 and 41,230 base pairs with G+C content of 38 mol% and 37.9 mol% and contain 88 and 83 coding sequences, respectively. Transmission electron microscopy showed the icosahedral capsid and contractile tail of the phages and genomic analysis predicted that both phages have myovirus morphology and belong to the class Caudoviricetes. Genomic analysis suggested the therapeutic safety of these phages, as they do not have bacterial virulence factors, antimicrobial resistance genes or lysogenic genes, suggesting that they are potential candidates for phage therapy. The in vivo study demonstrated a high survival rate in the phage cocktail treatment group compared to the control group. Our findings support the potential application of phage therapy as an alternative therapeutic treatment against lung infections caused by carbapenem-resistant A. baumannii.
Insights
Two novel phages, Srynta and Nolivar, show promise for treating carbapenem-resistant Acinetobacter baumannii lung infections. Phage therapy demonstrated increased survival rates in a mouse model, offering a potential alternative to antibiotics.
Area of Science:
- Microbiology
- Virology
- Infectious Diseases
Background:
- Acinetobacter baumannii poses a significant threat due to high morbidity, mortality, and increasing carbapenem resistance.
- Existing antibiotic treatments are becoming less effective against this multidrug-resistant pathogen.
Purpose of the Study:
- To isolate and characterize novel lytic phages against Acinetobacter baumannii.
- To evaluate the therapeutic potential of these phages, Srynta and Nolivar, for treating pneumonia caused by carbapenem-resistant strains.
Main Methods:
- Isolation and in vitro characterization of lytic phages Srynta and Nolivar from sewage.
- Genomic sequencing, transmission electron microscopy, and in vivo efficacy assessment in a mouse pneumonia model.
Main Results:
- Both phages exhibited efficient adsorption, lytic activity, short latent periods, and high burst sizes in vitro.
- Genomic analysis revealed linear dsDNA genomes, myovirus morphology, and absence of virulence, resistance, or lysogenic genes, indicating therapeutic safety.
- In vivo studies showed significantly improved survival rates in mice treated with a phage cocktail compared to controls.
Conclusions:
- Phages Srynta and Nolivar are safe and effective candidates for phage therapy against Acinetobacter baumannii.
- Phage therapy presents a viable alternative treatment for lung infections caused by carbapenem-resistant Acinetobacter baumannii.
