Bacteriophage Effectively Rescues Pneumonia Caused by Prevalent Multidrug-Resistant Klebsiella pneumoniae in the Early Stage. 2022

Lin Gan, and Hanyu Fu, and Ziyan Tian, and Jinghua Cui, and Chao Yan, and Guanhua Xue, and Zheng Fan, and Bing Du, and Junxia Feng, and Hanqing Zhao, and Yanling Feng, and Ziying Xu, and Tongtong Fu, and Xiaohu Cui, and Rui Zhang, and Shuheng Du, and Shiyu Liu, and Yao Zhou, and Qun Zhang, and Ling Cao, and Jing Yuan
Department of Bacteriology, Capital Institute of Pediatricsgrid.418633.b, Beijing, China.

Pneumonia caused by multidrug-resistant (MDR) Klebsiella pneumoniae of sequence types ST11 and ST383 have highlighted the necessity for new therapies against these prevalent pathogens. Bacteriophages (phages) may be used as alternatives or complements to antibiotics for treating MDR bacteria because they show potential efficacy in mouse models and even individual clinical cases, and they also cause fewer side effects, such as microbiota-imbalance-induced diseases. In the present study, we screened two phages, pKp11 and pKp383, that targeted ST11 and ST383 MDR K. pneumoniae isolates collected from patients with pneumonia, and they exhibited a broad host range, high lytic activity, and high environmental adaptability. Both phages pKp11 and pKp383 provided an effective treatment for the early stage of pneumonia in a murine infection model without promoting obvious side effects, and cocktails consisting of the two phages were more effective for reducing bacterial loads, inflammation, and pathogenic injuries. Our findings support the application of phages as new medications for refractory ST11 and ST383 K. pneumoniae infections and emphasize the potential of enhancing phage therapy modalities through phage screening. These data provided important resources for assessing and optimizing phage therapies for MDR ST11 and ST383 infection treatment. However, substantial amounts of further work are needed before phage therapy can be translated to human therapeutics. IMPORTANCE K. pneumoniae is recognized as the most common pathogen of hospital- and community-acquired pneumonia across the world. The strains of ST11 and ST383 are frequently reported in patients with pneumonia. However, the efficacy of antibiotics toward K. pneumoniae is decreasing dramatically. As a new approach to combat MDR bacteria, phages have exhibited positive clinical effects and efficacy as synergetic or alternative strategies to antibiotics. Thus, we screened two phages that targeted ST11 and ST383 MDR K. pneumoniae, and they exhibited a broad host range, high lytic activity, and high environmental adaptability. Both phages provided an effective treatment for the early stage of pneumonia in mice, and cocktails consisting of the two phages were more effective in reducing bacterial loads, inflammation, and pathogenic injuries. Although these data suggest that phages are effective alternatives or complements to antibiotics, more research is needed before they can be translated into therapeutics for humans.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007710 Klebsiella Infections Infections with bacteria of the genus KLEBSIELLA. Infections, Klebsiella,Infection, Klebsiella,Klebsiella Infection
D007711 Klebsiella pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Bacillus pneumoniae,Bacterium pneumoniae crouposae,Hyalococcus pneumoniae,Klebsiella pneumoniae aerogenes,Klebsiella rhinoscleromatis
D011014 Pneumonia Infection of the lung often accompanied by inflammation. Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001435 Bacteriophages Viruses whose hosts are bacterial cells. Phages,Bacteriophage,Phage
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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