Disease Information

General Information of the Disease (ID: DIS00010)

• Name: Shigellosis
• ICD: ICD-11: 1A02

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  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) 2 drug(s) in total

Nalidixic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.A85T
• Resistant Drug: Nalidixic acid
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.D111H
• Resistant Drug: Nalidixic acid
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.S129P
• Resistant Drug: Nalidixic acid
• 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 gyrase subunit A (GYRA) [1]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.N57K
• Resistant Drug: Nalidixic acid
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.H80P
• Resistant Drug: Nalidixic acid
• 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.

Norfloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.N57K
• Resistant Drug: Norfloxacin
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.H80P
• Resistant Drug: Norfloxacin
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.A85T
• Resistant Drug: Norfloxacin
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.D111H
• Resistant Drug: Norfloxacin
• 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]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Missense mutation; p.S129P
• Resistant Drug: Norfloxacin
• 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.

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

Microcin J25

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC transporter ATP-binding/permease protein YojI (YOJI) [2]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Microcin J25
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli k-12; 83333
• Experiment for Molecule Alteration: Promega and one-step chromosomal gene inactivation method assay
• Experiment for Drug Resistance: Spot-on-lawn assay
• Mechanism Description: YojI, an Escherichia coli open reading frame with an unknown function, mediates resistance to the peptide antibiotic microcin J25 when it is expressed from a multicopy vector. Disruption of the single chromosomal copy of yojI increased sensitivity of cells to microcin J25. One obvious explanation for the protective effect against microcin J25 is that YojI action keeps the intracellular concentration of the peptide below a toxic level. the resistance to MccJ25 mediated by YojI involves extrusion of the peptide and that YojI is assisted by the multifunctional outer membrane protein TolC.

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: YojI of Escherichia coli functions as a microcin J25 efflux pump. J Bacteriol. 2005 May;187(10):3465-70. doi: 10.1128/JB.187.10.3465-3470.2005.