High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85135182637
Pubmed ID
35902639
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Shein A.M.S., Wannigama D.L., Higgins P.G., Hurst C., Abe S., Hongsing P., Chantaravisoot N., Saethang T., Luk-in S., Liao T., Nilgate S., Rirerm U., Kueakulpattana N., Srisakul S., Aryukarn A., Laowansiri M., Hao L.Y., Yonpiam M., Ragupathi N.K.D., Techawiwattanaboon T., Ngamwongsatit N., Amarasiri M., Ounjai P., Kupwiwat R., Phattharapornjaroen P., Badavath V.N., Leelahavanichkul A., Kicic A., Chatsuwan T. High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-17083-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86403
Title
High prevalence of mgrB-mediated colistin resistance among carbapenem-resistant Klebsiella pneumoniae is associated with biofilm formation, and can be overcome by colistin-EDTA combination therapy
Author(s)
Shein A.M.S.
Wannigama D.L.
Higgins P.G.
Hurst C.
Abe S.
Hongsing P.
Chantaravisoot N.
Saethang T.
Luk-in S.
Liao T.
Nilgate S.
Rirerm U.
Kueakulpattana N.
Srisakul S.
Aryukarn A.
Laowansiri M.
Hao L.Y.
Yonpiam M.
Ragupathi N.K.D.
Techawiwattanaboon T.
Ngamwongsatit N.
Amarasiri M.
Ounjai P.
Kupwiwat R.
Phattharapornjaroen P.
Badavath V.N.
Leelahavanichkul A.
Kicic A.
Chatsuwan T.
Wannigama D.L.
Higgins P.G.
Hurst C.
Abe S.
Hongsing P.
Chantaravisoot N.
Saethang T.
Luk-in S.
Liao T.
Nilgate S.
Rirerm U.
Kueakulpattana N.
Srisakul S.
Aryukarn A.
Laowansiri M.
Hao L.Y.
Yonpiam M.
Ragupathi N.K.D.
Techawiwattanaboon T.
Ngamwongsatit N.
Amarasiri M.
Ounjai P.
Kupwiwat R.
Phattharapornjaroen P.
Badavath V.N.
Leelahavanichkul A.
Kicic A.
Chatsuwan T.
Author's Affiliation
Yamagata Prefectural Central Hospital
Medizinische Fakultät
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Perth Children's Hospital
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Chulalongkorn University
Sahlgrenska Akademin
Kasetsart University
Mae Fah Luang University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Mahidol University
Kitasato University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
Telethon Kids Institute
Partner Site Bonn-Cologne
Medizinische Fakultät
Siriraj Hospital
Mae Fah Luang University Hospital
UWA Medical School
Perth Children's Hospital
The Faculty of Health Sciences
Narsee Monjee Institute of Management Studies, Mumbai
Chulalongkorn University
Sahlgrenska Akademin
Kasetsart University
Mae Fah Luang University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Mahidol University
Kitasato University
Charles Darwin University
Faculty of Medicine, Chulalongkorn University
The University of Sheffield
Christian Medical College, Vellore
Telethon Kids Institute
Partner Site Bonn-Cologne
Other Contributor(s)
Abstract
The global prevalence of colistin-resistant Klebsiella pneumoniae (ColRkp) facilitated by chromosomal and plasmid-mediated Ara4N or PEtN-remodeled LPS alterations has steadily increased with increased colistin usage for treating carbapenem-resistant K. pneumoniae (CRkp). Our study demonstrated the rising trend of ColRkp showing extensively and pandrug-resistant characteristics among CRkp, with a prevalence of 28.5%, which was mediated by chromosomal mgrB, pmrB, or phoQ mutations (91.5%), and plasmid-mediated mcr-1.1, mcr-8.1, mcr-8.2 alone or in conjunction with R256G PmrB (8.5%). Several genetic alterations in mgrB (85.1%) with increased expressions of Ara4N-related phoPQ and pmrK were critical for establishing colistin resistance in our isolates. In this study, we discovered the significant associations between extensively drug-resistant bacteria (XDR) and pandrug-resistant bacteria (PDR) ColRkp in terms of moderate, weak or no biofilm-producing abilities, and altered expressions of virulence factors. These ColRkp would therefore be very challenging to treat, emphasizing for innovative therapy to combat these infections. Regardless of the underlying colistin-resistant mechanisms, colistin-EDTA combination therapy in this study produced potent synergistic effects in both in vitro and in vivo murine bacteremia, with no ColRkp regrowth and improved animal survival, implying the significance of colistin-EDTA combination therapy as systemic therapy for unlocking colistin resistance in ColRkp-associated bacteremia.