Shein, Aye Mya Sithu, Wannigama, Dhammika Leshan ORCID: 0000-0001-6316-1221, Higgins, Paul G., Hurst, Cameron, Abe, Shuichi, Hongsing, Parichart, Chantaravisoot, Naphat, Saethang, Thammakorn, Luk-in, Sirirat, Liao, Tingting, Nilgate, Sumanee, Rirerm, Ubolrat, Kueakulpattana, Naris, Srisakul, Sukrit, Aryukarn, Apichaya, Laowansiri, Matchima, Hao, Lee Yin, Yonpiam, Manta, Ragupathi, Naveen Kumar Devanga, Techawiwattanaboon, Teerasit, Ngamwongsatit, Natharin, Amarasiri, Mohan ORCID: 0000-0002-3509-3433, Ounjai, Puey, Kupwiwat, Rosalyn, Phattharapornjaroen, Phatthranit, Badavath, Vishnu Nayak, Leelahavanichkul, Asada, Kicic, Anthony ORCID: 0000-0002-0008-9733 and Chatsuwan, Tanittha (2022). 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. Sci Rep, 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shein, Aye Mya SithuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wannigama, Dhammika LeshanUNSPECIFIEDorcid.org/0000-0001-6316-1221UNSPECIFIED
Higgins, Paul G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurst, CameronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abe, ShuichiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hongsing, ParichartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chantaravisoot, NaphatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saethang, ThammakornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luk-in, SiriratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liao, TingtingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nilgate, SumaneeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rirerm, UbolratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kueakulpattana, NarisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srisakul, SukritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aryukarn, ApichayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laowansiri, MatchimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hao, Lee YinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yonpiam, MantaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ragupathi, Naveen Kumar DevangaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Techawiwattanaboon, TeerasitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ngamwongsatit, NatharinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amarasiri, MohanUNSPECIFIEDorcid.org/0000-0002-3509-3433UNSPECIFIED
Ounjai, PueyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kupwiwat, RosalynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phattharapornjaroen, PhatthranitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Badavath, Vishnu NayakUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leelahavanichkul, AsadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kicic, AnthonyUNSPECIFIEDorcid.org/0000-0002-0008-9733UNSPECIFIED
Chatsuwan, TanitthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-695572
DOI: 10.1038/s41598-022-17083-5
Journal or Publication Title: Sci Rep
Volume: 12
Number: 1
Date: 2022
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GRAM-NEGATIVE BACTERIA; MULTIPLEX PCR; INSERTIONAL INACTIVATION; ACINETOBACTER-BAUMANNII; STAPHYLOCOCCUS-AUREUS; VIRULENCE; PHOSPHOETHANOLAMINE; EMERGENCE; MECHANISM; SINGLEMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69557

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