Scientific Reports (Nov 2024)
Phage cocktail amikacin combination as a potential therapy for bacteremia associated with carbapenemase producing colistin resistant Klebsiella pneumoniae
- 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
Affiliations
- Aye Mya Sithu Shein
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Dhammika Leshan Wannigama
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Cameron Hurst
- Molly Wardaguga Research Centre, Charles Darwin University
- Peter N. Monk
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School
- Mohan Amarasiri
- Department of Civil and Environmental Engineering, Graduate School of Engineering, Tohoku University
- Thidathip Wongsurawat
- Siriraj Long-Read Lab (Si-LoL), Division of Medical Bioinformatics, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University
- Piroon Jenjaroenpun
- Siriraj Long-Read Lab (Si-LoL), Division of Medical Bioinformatics, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University
- Phatthranit Phattharapornjaroen
- Faculty of Health Science Technology, Chulabhorn Royal Academy
- William Graham Fox Ditcham
- Faculty of Health and Medical Sciences, School of Medicine, The University of Western Australia
- Puey Ounjai
- Department of Biology, Faculty of Science, Mahidol University
- Thammakorn Saethang
- Department of Computer Science, Faculty of Science, Kasetsart University
- Naphat Chantaravisoot
- Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University
- Vishnu Nayak Badavath
- School of Pharmacy and Technology Management, SVKM’s Narsee Monjee Institute of Management Studies (NMIMS)
- Sirirat Luk-in
- Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University
- Sumanee Nilgate
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Ubolrat Rirerm
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Sukrit Srisakul
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Naris Kueakulpattana
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Matchima Laowansiri
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- S. M. Ali Hosseini Rad
- Department of Microbiology and Immunology, University of Otago
- Supaporn Wacharapluesadee
- Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital
- Apaporn Rodpan
- Program in Biotechnology, Faculty of Science, Chulalongkorn University
- Natharin Ngamwongsatit
- Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University
- Arsa Thammahong
- Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University
- Hitoshi Ishikawa
- Yamagata Prefectural University of Health Sciences
- Robin James Storer
- Office of Research Affairs, Faculty of Medicine, Chulalongkorn University
- Asada Leelahavanichkul
- Center of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University
- Naveen Kumar Devanga Ragupathi
- Biofilms and Antimicrobial Resistance Consortium of ODA Receiving Countries, The University of Sheffield
- Annika Y. Classen
- Department for Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Talerngsak Kanjanabuch
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University
- Daniel Pletzer
- Department of Microbiology and Immunology, University of Otago
- Kazuhiko Miyanaga
- Division of Bacteriology, School of Medicine, Jichi Medical University
- Longzhu Cui
- Division of Bacteriology, School of Medicine, Jichi Medical University
- Hiroshi Hamamoto
- Department of Infectious Diseases, Faculty of Medicine, Yamagata University
- Paul G. Higgins
- Faculty of Medicine and University Hospital Cologne, Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne
- Anthony Kicic
- Telethon Kids Institute, University of Western Australia
- Tanittha Chatsuwan
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
- Parichart Hongsing
- School of Integrative Medicine, Mae Fah Luang University
- Shuichi Abe
- Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital
- DOI
- https://doi.org/10.1038/s41598-024-79924-9
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 20
Abstract
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.
Keywords
- Klebsiella pneumoniae
- Carbapenemase
- Colistin resistance
- Extensively drug-resistant
- Phage cocktail
- Phage cocktail-antibiotic combination
