Disease Information

General Information of the Disease (ID: DIS00045)

• Name: Sepsis
• ICD: ICD-11: 1G40

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 8 drug(s) in total

Bacitracin A

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Undecaprenyl-diphosphatase BcrC (BCRC) [1]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Bacillus subtilis 168; 224308
• In Vitro Model: Bacillus subtilis BFS82; 1423
• In Vitro Model: Bacillus subtilis BSmrs168; 1423
• In Vitro Model: Bacillus subtilis BSmrs173; 1423
• In Vitro Model: Bacillus subtilis BSmrs175; 1423
• In Vitro Model: Bacillus subtilis BSmrs194; 1423
• In Vitro Model: Bacillus subtilis BSmrs201; 1423
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: Microtiter tray assay
• Mechanism Description: Overexpression of the BcrCBs protein, formerly called YwoA, in Escherichia coli or in Bacillus subtilis allows these bacteria to stand higher concentrations of bacitracin.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Bacitracin F

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Undecaprenyl-diphosphatase BcrC (BCRC) [1]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Bacillus subtilis 168; 224308
• In Vitro Model: Bacillus subtilis BFS82; 1423
• In Vitro Model: Bacillus subtilis BSmrs168; 1423
• In Vitro Model: Bacillus subtilis BSmrs173; 1423
• In Vitro Model: Bacillus subtilis BSmrs175; 1423
• In Vitro Model: Bacillus subtilis BSmrs194; 1423
• In Vitro Model: Bacillus subtilis BSmrs201; 1423
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: Microtiter tray assay
• Mechanism Description: Overexpression of the BcrCBs protein, formerly called YwoA, in Escherichia coli or in Bacillus subtilis allows these bacteria to stand higher concentrations of bacitracin.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Bacitracin methylene disalicylate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Undecaprenyl-diphosphatase BcrC (BCRC) [1]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin methylene disalicylate
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Bacillus subtilis 168; 224308
• In Vitro Model: Bacillus subtilis BFS82; 1423
• In Vitro Model: Bacillus subtilis BSmrs168; 1423
• In Vitro Model: Bacillus subtilis BSmrs173; 1423
• In Vitro Model: Bacillus subtilis BSmrs175; 1423
• In Vitro Model: Bacillus subtilis BSmrs194; 1423
• In Vitro Model: Bacillus subtilis BSmrs201; 1423
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: Microtiter tray assay
• Mechanism Description: Overexpression of the BcrCBs protein, formerly called YwoA, in Escherichia coli or in Bacillus subtilis allows these bacteria to stand higher concentrations of bacitracin.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin methylene disalicylate
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Bacitracin methylene disalicylate
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli.

Dibekacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [3]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Dibekacin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Gentamicin A

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [3]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Gentamicin A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Kanamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [3]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Kanamycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Sisomicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [3]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Sisomicin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Tobramycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [3]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Tobramycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Investigative Drug(s) 5 drug(s) in total

Hydrochloride

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA) (Malat1) [4]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Hydrochloride
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: RAW 264.7; Ascites; Mus musculus (Mouse); CVCL_0493
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter assay
• Mechanism Description: Hsa-miR-346 plays a role in the development of sepsis by downregulating SMAD3 expression and is negatively regulated by LncRNA MALAT1.

Lipopolysaccharide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [5]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Lipopolysaccharide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; Luciferase assay; RNA pull down assay
• Mechanism Description: Silence of NEAT1 suppressed LPS-induced inflammatory response of macrophages by mediating miR-17-5p and TLR4, indicating that NEAT1 might be a promising target for sepsis treatment.

Key Molecule: Maternally expressed 3 (MEG3) [6]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Up-regulation; Expression
• Resistant Drug: Lipopolysaccharide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: AC16 cells; Heart; Homo sapiens (Human); CVCL_4U18
• In Vitro Model: Human primary renal mixed epithelial cells (ATCC? PCS-400-012?); N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Overexpression assay; Knockdown assay
• Experiment for Drug Resistance: Flow cytometry assay assay
• Mechanism Description: LncRNA MEG3 overexpression may be involved in sepsis, and the downregulation of LncRNA MEG3 may serve as a potential therapeutic target for sepsis.

Key Molecule: H19, imprinted maternally expressed transcript (H19) [7]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Down-regulation; Interaction
• Resistant Drug: Lipopolysaccharide
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: UL-1 cells; Ascites; Canis lupus familiaris (Dog); CVCL_L421
• In Vivo Model: Male BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Overexpression assay
• Mechanism Description: LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis.

Midecamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Oleandomycin glycosyltransferase oleD (OLED) [8]

• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Molecule Alteration: Expression; Acquired
• Resistant Drug: Midecamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: T7 express cells; Lung; Mus musculus (Mouse); CVCL_4314
• Experiment for Molecule Alteration: SDS-PAGE analysis
• Experiment for Drug Resistance: Broth microdilution antifungal susceptibility test assay

Streptothricin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Streptothricin acetyltransferase (STA) [9]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Streptothricin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Bacillus subtilis strain RM141; 1423
• In Vitro Model: Escherichia coli strain 5131-5; 562
• Experiment for Molecule Alteration: [a-32P] dCTP by the dideoxynucleoside triphosphate chain termination method assay
• Mechanism Description: The nucleotide sequence of the streptothricin acetyltransferase (STAT) gene from streptothricin-producing Streptomyces lavendulae predicts a 189-amino-acid protein of molecular weight 20,000, which is consistent with that determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme. By addition of promoter signals and a synthetic ribosome-binding (Shine-Dalgarno) sequence at an appropriate position upstream of the STAT translational start codon, the STAT gene confers streptothricin resistance on Escherichia coli and Bacillus subtilis.

Tunicamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tunicamycin resistance protein (TMRB) [10]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tunicamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacillus subtilis strain; 1423
• In Vitro Model: Escherichia coli strain; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: Overproduction of TmrB protein, a 22.5-kDa protein with an N-terminal ATP-binding region and a C-terminal amphiphilic alpha-helix, confers resistance to tunicamycin on Bacillus subtilis. TmrB protein was found to bind Sepharose 6B to which tunicamycin was covalently linked. Experiments with mutant proteins found that the C-terminal region of TmrB protein might be involved in the binding to tunicamycin.

References

• Ref 1: BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in bacitracin resistance. J Biol Chem. 2005 Aug 12;280(32):28852-7. doi: 10.1074/jbc.M413750200. Epub 2005 Jun 9.
• Ref 2: Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol. 1995 Jun;16(5):969-76. doi: 10.1111/j.1365-2958.1995.tb02322.x.
• Ref 3: Novel aminoglycoside 2''-phosphotransferase identified in a gram-negative pathogen. Antimicrob Agents Chemother. 2013 Jan;57(1):452-7. doi: 10.1128/AAC.02049-12. Epub 2012 Nov 5.
• Ref 4: Knockdown of lncRNA MALAT1 alleviates bupivacaine-induced neurotoxicity via the miR-101-3p/PDCD4 axisLife Sci. 2019 Sep 1;232:116606. doi: 10.1016/j.lfs.2019.116606. Epub 2019 Jun 27.
• Ref 5: NEAT1 regulates MPP(+)-induced neuronal injury by targeting miR-124 in neuroblastoma cellsNeurosci Lett. 2019 Aug 24;708:134340. doi: 10.1016/j.neulet.2019.134340. Epub 2019 Jun 19.
• Ref 6: LncRNA MEG3 contributes to adenosine-induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K-AKT-mTOR and beclin-1 signaling pathwayJ Cell Biochem. 2019 Oct;120(10):18172-18185. doi: 10.1002/jcb.29123. Epub 2019 May 29.
• Ref 7: Downregulation of lncRNA H19 sensitizes melanoma cells to cisplatin by regulating the miR-18b/IGF1 axisAnticancer Drugs. 2020 Jun;31(5):473-482. doi: 10.1097/CAD.0000000000000888.
• Ref 8: Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site .Int J Mol Sci. 2021 Nov 23;22(23):12636. doi: 10.3390/ijms222312636. 10.3390/ijms222312636
• Ref 9: Nucleotide sequence of the streptothricin acetyltransferase gene from Streptomyces lavendulae and its expression in heterologous hosts. J Bacteriol. 1987 May;169(5):1929-37. doi: 10.1128/jb.169.5.1929-1937.1987.
• Ref 10: TmrB protein, which confers resistance to tunicamycin on Bacillus subtilis, binds tunicamycin. Biosci Biotechnol Biochem. 1995 Feb;59(2):321-2. doi: 10.1271/bbb.59.321.