Molecule Information

General Information of the Molecule (ID: Mol00739)

• Name: Transcriptional regulatory protein (PHOP) ,Klebsiella pneumoniae
• Synonyms: phoP; PhoP
• Molecule Type: Protein
• Gene Name: phoP
• Sequence:
  MRVLVVEDNALLRHHLKVQLQELGHQVDAAEDAREADYYLGEHLPDIAIVDLGLPDEDGL
  SLIRRWRSHDVSLPVLVLTAREGWQDKVEVLSAGADDYVTKPFHIEEVAARMQALLRRNS
  GLASQVISLPPFQVDLSRRELSVNDQPIKLTAFEYTIMETLIRNRGKVVSKDSLMLQLYP
  DAELRESHTIYVLMGRLRKKIQAEYPQDVITTVRGQGYLFELR
• Uniprot ID: A0A139ZN42_KLEPN

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Klebsiella
Species: Klebsiella pneumoniae

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Colistin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Klebsiella pneumoniae [1]

• Resistant Disease: Klebsiella pneumoniae [ICD-11: CA40.0]
• Resistant Drug: Colistin
• Molecule Alteration: Missense mutation; p.D191Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Klebsiella pneumoniae kp75; 573
• In Vitro Model: Klebsiella pneumoniae ATCC 53153; 573
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutated protein PhoP activates the transcription of the pmrHFIJkLM operon, the product of which leads to synthesis of L-amino-arabinose and ultimately to colistin resistance in k. pneumoniae.These modifications create a more positively charged lipopolysaccharide and thus reduce the affinity of LPS to positively charged polymyxins.

Disease Class: Klebsiella pneumoniae infection [1]

• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Resistant Drug: Colistin
• Molecule Alteration: Missense mutation; p.D191Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Klebsiella pneumoniae kp75; 573
• In Vitro Model: Klebsiella pneumoniae ATCC 53153; 573
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutated protein PhoP activates the transcription of the pmrHFIJkLM operon, the product of which leads to synthesis of L-amino-arabinose and ultimately to colistin resistance in k. pneumoniae.These modifications create a more positively charged lipopolysaccharide and thus reduce the affinity of LPS to positively charged polymyxins.

Disease Class: Klebsiella pneumoniae infection [1]

• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Resistant Drug: Colistin
• Molecule Alteration: Missense mutation; p.D191Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Klebsiella pneumoniae kp75; 573
• In Vitro Model: Klebsiella pneumoniae ATCC 53153; 573
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutated protein PhoP activates the transcription of the pmrHFIJkLM operon, the product of which leads to synthesis of L-amino-arabinose and ultimately to colistin resistance in k. pneumoniae.These modifications create a more positively charged lipopolysaccharide and thus reduce the affinity of LPS to positively charged polymyxins.

References

• Ref 1: Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system. Antimicrob Agents Chemother. 2015 May;59(5):2780-4. doi: 10.1128/AAC.05055-14. Epub 2015 Mar 2.