| Autor: |
Aye Mya Sithu Shein, Dhammika Leshan Wannigama, Cameron Hurst, Peter N. Monk, Mohan Amarasiri, Thidathip Wongsurawat, Piroon Jenjaroenpun, Phatthranit Phattharapornjaroen, William Graham Fox Ditcham, Puey Ounjai, Thammakorn Saethang, Naphat Chantaravisoot, Vishnu Nayak Badavath, Sirirat Luk-in, Sumanee Nilgate, Ubolrat Rirerm, Sukrit Srisakul, Naris Kueakulpattana, Matchima Laowansiri, S. M. Ali Hosseini Rad, Supaporn Wacharapluesadee, Apaporn Rodpan, Natharin Ngamwongsatit, Arsa Thammahong, Hitoshi Ishikawa, Robin James Storer, Asada Leelahavanichkul, Naveen Kumar Devanga Ragupathi, Annika Y. Classen, Talerngsak Kanjanabuch, Daniel Pletzer, Kazuhiko Miyanaga, Longzhu Cui, Hiroshi Hamamoto, Paul G. Higgins, Anthony Kicic, Tanittha Chatsuwan, Parichart Hongsing, Shuichi Abe |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 14, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-024-79924-9 |
| Popis: |
Abstract The increasing occurrence of hospital-associated infections, particularly bacteremia, caused by extensively drug-resistant (XDR) carbapenemase-producing colistin-resistant Klebsiella pneumoniae highlights a critical requirement to discover new therapeutic alternatives. Bacteriophages having host-specific bacteriolytic effects are promising alternatives for combating these pathogens. Among 12 phages isolated from public wastewater in Thailand, two phages-vB_kpnM_05 (myovirus) and vB_kpnP_08 (podovirus) showed broad-host range, producing bacteriolytic activities against 81.3% (n = 26) and 78.1% (n = 25) of 32 XDR carbapenemase-producing colistin-resistant K. pneumoniae, with capsular types—K15, K17, K50, K51, K52/wzi-50 and K2/wzi-2. Both phages showed short replication times, large burst sizes with rapid adsorptions. They exhibited significant stability under various environmental conditions. Genomic analysis revealed that both phages are genetically distinct phages from Myoviridae and Podoviridae family, with the lack of toxin, virulence, lysogeny and antibiotic resistance genes. These characteristics highlighted their promising potential for utilizing in phage therapy for combating XDR K. pneumoniae. Although phage cocktail combining vB_kpnM_05 and vB_kpnP_08 provided significant bacteriolysis for longer duration (8 h) than its monophage (6 h), bacterial regrowth was observed which suggested an evitable development of phage resistance under phages’ selection pressures. Future study will be undertaken to elucidate the precise mechanisms by which these XDR K. pneumoniae developed phage resistance and their associated fitness cost. Remarkably, combining phage cocktail with amikacin at their sub-inhibitory concentrations produced potent synergy by completely suppressing bacterial regrowth in vitro. Our study demonstrated the significant therapeutic and prophylactic effectiveness of a phage cocktail-amikacin combination as a promising alternative strategy for overcoming bacteremia associated with XDR K. pneumoniae having carbapenemase and colistin resistance in vivo. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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