Drug Information

Drug (ID: DG00240) and It's Reported Resistant Information

• Name: Norfloxacin
• Synonyms: Baccidal; Barazan; Chibroxin; Fulgram; Lexinor; NFLX; Norflo; Norfloxacine; Norfloxacino; Norfloxacinum; Noroxin; Sebercim; Merck Brand of Norfloxacin; Norfloxacin Merck Brand; AM 0715; AM 715; AM0715; MK 0366; MK 366; MK0366; MK366; AM-0715; AM-715; Chibroxin (TN); Insensye (TN); MK-0366; MK-366; Norflohexal (TN); Norfloxacine [INN-French]; Norfloxacino [INN-Spanish]; Norfloxacinum [INN-Latin]; Norfocin (TN); Noroxin (TN); Nufloxib (TN); Roxin (TN); Utin (TN); Utinor (TN); Apo-Norflox (TN); Norfloxacin (JP15/USP/INN); Norfloxacin [USAN:BAN:INN:JAN]; Chibroxin, MK-366, Baccidal, Sebercim, Zoroxin, Norfloxacin; 1,4-Dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid; 1-Ethyl-6-fluor-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-chinolincarbonsaeure; 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid; 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-[1-piperazinyl]-3-quinoline-carboxylic acid; 1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid; 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydroquinoline-3-carboxylic acid; 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (8 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2], [3], [4]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [5]
  Melioidosis [ICD-11: 1C42]; [6], [7]
  Pneumonia [ICD-11: CA40]; [8]
  Pyelonephritis [ICD-11: GB54]; [9]
  Salmonellosis [ICD-11: 1A09]; [10]
  Shigellosis [ICD-11: 1A02]; [1]
  Staphylococcus meningitis [ICD-11: 1B54]; [11]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Clostridioides difficile intestinal infection [ICD-11: 1A04]; [12]
• Target: Bacterial DNA gyrase (Bact gyrase); GYRA_STAAU GYRB_STAAU; [1]
• Formula: C16H18FN3O3
• IsoSMILES: CCN1C=C(C(=O)C2=CC(=C(C=C21)N3CCNCC3)F)C(=O)O
• InChI: 1S/C16H18FN3O3/c1-2-19-9-11(16(22)23)15(21)10-7-12(17)14(8-13(10)19)20-5-3-18-4-6-20/h7-9,18H,2-6H2,1H3,(H,22,23)
• InChIKey: OGJPXUAPXNRGGI-UHFFFAOYSA-N
• PubChem CID: 4539
• ChEBI ID: CHEBI:100246
• TTD Drug ID: D0Q2PE
• VARIDT ID: DR01204
• INTEDE ID: DR1176
• DrugBank ID: DB01059

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.S83L
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain N-112; 562
• In Vitro Model: Escherichia coli strain N-118; 562
• In Vitro Model: Escherichia coli strain N-119; 562
• In Vitro Model: Escherichia coli strain N-51; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.S83W
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain P-18; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.D87N
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain N-113; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.G81C
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain N-97; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.A84P
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain P-5; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.A67S
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain P-10; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Key Molecule: DNA gyrase subunit A (GYRA) [2], [3], [4]

• Molecule Alteration: Missense mutation; p.Q106H
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain kL16; 1425342
• In Vitro Model: Escherichia coli strain N-89; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Quinolones are considered to exert antibacterial activity by inhibiting DNA gyrase (EC 5.99.1.3), which catalyzes topological changes of DNA.DNA gyrase of Escherichia coli consists of subunits A and B, which are the products of the gyrA and gyrB genes, respectively. Mutations in either gene can cause quinolone resistance.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [13]

• Molecule Alteration: Missense mutation; p.S463A
• Resistant Disease: Morganella morganii infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Morganella morganii isolate; 582
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC,parE) genes result in quinolone susceptibility.

Key Molecule: DNA topoisomerase 4 subunit B (PARE) [13]

• Molecule Alteration: Missense mutation; p.S464Y
• Resistant Disease: Morganella morganii infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Morganella morganii isolate; 582
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC,parE) genes result in quinolone susceptibility.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [13]

• Molecule Alteration: Missense mutation; p.S80I
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Morganella morganii isolate; 582
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The mutations in DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC,parE) genes result in quinolone susceptibility.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Quinolone efflux pump (QEPA2) [14]

• Molecule Alteration: Missense mutation; p.A99G+p.V134I
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: QepA confers decreased susceptibility to hydrophilic fluoroquinolones (e.g., norfloxacin, ciprofloxacin, and enrofloxacin) with a 32- to 64-fold increase of MICs.

Shigellosis [ICD-11: 1A02]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Molecule Alteration: Missense mutation; p.N57K
• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Molecule Alteration: Missense mutation; p.H80P
• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.A85T
• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.D111H
• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1]

• Molecule Alteration: Missense mutation; p.S129P
• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Quinolone resistance protein NorA (NORA) [5]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Staphylococcus aureus strain SA113; 1280
• Experiment for Molecule Alteration: Dideoxy chain-termination method assay
• Mechanism Description: The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. Escherichia coli strains containing one of the plasmids carrying the norA gene (pTUS1, pTUS180, pTUS829, and pTUS206) were 8 to 64 times more resistant to the hydrophilic quinolones than the parent quinolone-susceptible strain.

Clostridioides difficile intestinal infection [ICD-11: 1A04]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug export protein MepA (cdeA) [12]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In C. difficile, two secondary active transporters belonging to the MFS and MATE families have been reported to be associated with drug resistance. Heterologous expression of the clostridial Cme protein in the MFS subfamily promotes ERY resistance in Enterococcus faecalis. A sodium-dependent efflux pump of the MATE subfamily encoded by the cdeA gene of C. difficile attributes resistance to norfloxacin and ciprofloxacin when the gene was overexpressed in Escherichia coli.

Salmonellosis [ICD-11: 1A09]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug transporter MdfA (MDFA) [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Salmonella enterica infection [ICD-11: 1A09.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enterica serovar Typhimurium ATCC 14028s; 588858
• Experiment for Molecule Alteration: Quantitative real-time PCR
• Experiment for Drug Resistance: L agar plate method assay
• Mechanism Description: Overexpression or overproduction of mdfA confers drug resistance.

Key Molecule: Multidrug resistance protein MdtK (MDTK) [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Salmonella enterica infection [ICD-11: 1A09.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enterica serovar Typhimurium ATCC 14028s; 588858
• Experiment for Molecule Alteration: Quantitative real-time PCR
• Experiment for Drug Resistance: L agar plate method assay
• Mechanism Description: Overexpression or overproduction of mdtk confers drug resistance.

Staphylococcus meningitis [ICD-11: 1B54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Quinolone resistance protein NorB (NORB) [11]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: DNA microarray hybridization assay
• Experiment for Drug Resistance: Serial twofold agar dilutions assay
• Mechanism Description: MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant.

Key Molecule: Quinolone resistance protein NorA (NORA) [5]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Staphylococcus aureus strain SA113; 1280
• Experiment for Molecule Alteration: Dideoxy chain-termination method assay
• Mechanism Description: The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli.

Key Molecule: Quinolone resistance protein NorA (NORA) [5]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Staphylococcus aureus strain SA113; 1280
• Experiment for Molecule Alteration: Dideoxy chain-termination method assay
• Mechanism Description: The norA gene cloned from chromosomal DNA of quinolone-resistant Staphylococcus aureus Tk2566 conferred relatively high resistance to hydrophilic quinolones such as norfloxacin, enoxacin, ofloxacin, and ciprofloxacin, but only low or no resistance at all to hydrophobic ones such as nalidixic acid, oxolinic acid, and sparfloxacin in S. aureus and Escherichia coli. S. aureus SA113 (pTUS20) harboring a plasmid carrying the staphylococcal norA gene was 16 to 64 times more resistant to relatively hydrophilic quinolones.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: HTH-type transcriptional regulator MgrA (MGRA) [11]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: DNA microarray hybridization assay
• Experiment for Drug Resistance: Serial twofold agar dilutions assay
• Mechanism Description: MgrA was an indirect regulator of norB expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant.

Melioidosis [ICD-11: 1C42]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Outer membrane porin (OMP38) [6], [7]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Melioidosis [ICD-11: 1C42.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Burkholderia pseudomallei isolates; 28450
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Bps is highly resistant to many antimicrobial agents and this resistance may result from the low drug permeability of outer membrane proteins, known as porins.An Escherichia coli strain defective in most porins, but expressing BpsOmp38, exhibited considerably lower antimicrobial susceptibility than the control strain. In addition, mutation of Tyr119, the most prominent pore-lining residue in BpsOmp38, markedly altered membrane permeability, substitution with Ala (mutant BpsOmp38Y119A) enhanced uptake of the antimicrobial agents, while substitution with Phe (mutant BpsOmp38Y119F) inhibited uptake.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug efflux SMR transporter (ABES) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• Experiment for Molecule Alteration: Fluorometric efflux assay
• Experiment for Drug Resistance: Broth dilution assay
• Mechanism Description: The abeS gene product conferred resistance to various antimicrobial compounds through an efflux mechanism.

Key Molecule: MATE family efflux transporter (ABEM) [8]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AbeM was found to be an H+-coupled multidrug efflux pump and a unique member of the MATE family which lead to drug resistance.

References

• Ref 1: Novel mutations in quinolone resistance-determining regions of gyrA, gyrB, parC and parE in Shigella flexneri clinical isolates from eastern Chinese populations between 2001 and 2011. Eur J Clin Microbiol Infect Dis. 2016 Dec;35(12):2037-2045. doi: 10.1007/s10096-016-2761-2. Epub 2016 Sep 12.
• Ref 2: 4-Quinolone resistance mutations in the DNA gyrase of Escherichia coli clinical isolates identified by using the polymerase chain reaction. Antimicrob Agents Chemother. 1991 Feb;35(2):387-9. doi: 10.1128/AAC.35.2.387.
• Ref 3: Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990 Jun;34(6):1271-2. doi: 10.1128/AAC.34.6.1271.
• Ref 4: Cloning and characterization of a DNA gyrase A gene from Escherichia coli that confers clinical resistance to 4-quinolones. Antimicrob Agents Chemother. 1989 Jun;33(6):886-94. doi: 10.1128/AAC.33.6.886.
• Ref 5: Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol. 1990 Dec;172(12):6942-9. doi: 10.1128/jb.172.12.6942-6949.1990.
• Ref 6: Functional reconstitution, gene isolation and topology modelling of porins from Burkholderia pseudomallei and Burkholderia thailandensis. Biochem J. 2004 Feb 1;377(Pt 3):579-87. doi: 10.1042/BJ20031118.
• Ref 7: Porin involvement in cephalosporin and carbapenem resistance of Burkholderia pseudomallei. PLoS One. 2014 May 1;9(5):e95918. doi: 10.1371/journal.pone.0095918. eCollection 2014.
• Ref 8: AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters. Antimicrob Agents Chemother. 2005 Oct;49(10):4362-4. doi: 10.1128/AAC.49.10.4362-4364.2005.
• Ref 9: Study on risk factors, bacterial species, and drug resistance of acute pyelonephritis associated with ureteral stent after percutaneous nephrolithotomyEur J Clin Microbiol Infect Dis. 2021 Apr;40(4):707-713. doi: 10.1007/s10096-020-04050-z. Epub 2020 Oct 9.
• Ref 10: Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol. 2006 Jan;59(1):126-41. doi: 10.1111/j.1365-2958.2005.04940.x.
• Ref 11: MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005 Apr;187(7):2395-405. doi: 10.1128/JB.187.7.2395-2405.2005.
• Ref 12: Insights into drug resistance mechanisms in Clostridium difficile .Essays Biochem. 2017 Mar 3;61(1):81-88. doi: 10.1042/EBC20160062. Print 2017 Feb 28. 10.1042/EBC20160062
• Ref 13: Type II and type IV topoisomerase mutations in clinical isolates of Morganella morganii harbouring the qnrD gene. Ann Clin Microbiol Antimicrob. 2014 Aug 9;13:34. doi: 10.1186/s12941-014-0034-4.
• Ref 14: Plasmid-mediated quinolone resistance pump QepA2 in an Escherichia coli isolate from France. Antimicrob Agents Chemother. 2008 Oct;52(10):3801-4. doi: 10.1128/AAC.00638-08. Epub 2008 Jul 21.
• Ref 15: Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother. 2009 Dec;53(12):5312-6. doi: 10.1128/AAC.00748-09. Epub 2009 Sep 21.