Molecule Information

General Information of the Molecule (ID: Mol00976)

• Name: HTH-type transcriptional regulator MgrA (MGRA) ,Staphylococcus aureus
• Synonyms: Regulator of autolytic activity; norR; rat; SAOUHSC_00694
• Molecule Type: Protein
• Gene Name: mgrA
• Gene ID: 3920998
• Sequence:
  MSDQHNLKEQLCFSLYNAQRQVNRYYSNKVFKKYNLTYPQFLVLTILWDESPVNVKKVVT
  ELALDTGTVSPLLKRMEQVDLIKRERSEVDQREVFIHLTDKSETIRPELSNASDKVASAS
  SLSQDEVKELNRLLGKVIHAFDETKEK
• Function: Regulatory protein involved in autolytic activity, multidrug resistance and virulence. Controls autolysis by inactivating LytM, LytN (autolysins) and SarV (autolysis activator) and activating ArlRS, LrgAB and LytSR (autolysis inhibitors). Acts as a dual regulator for resistance to multiple drugs by inactivating NorB and tet38 and activating NorA. Positively controls the expression of virulence accessory gene regulator (agr) to promote alpha-hemolysin (hla) transcription and down-regulates staphylococcal accessory regulator (sarS), leading to repression of surface protein A (spa). Binds directly to hla promoter to augment its activation. Binds to sarS promoter to down-regulate spa expression.
• Uniprot ID: MGRA_STAA8

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Staphylococcaceae
Genus: Staphylococcus
Species: Staphylococcus aureus

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Expression; Up-regulation
• 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.

Moxifloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Moxifloxacin
• Molecule Alteration: Expression; Up-regulation
• 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.

Norfloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Norfloxacin
• Molecule Alteration: Expression; Up-regulation
• 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.

Sparfloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Sparfloxacin
• Molecule Alteration: Expression; Up-regulation
• 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.

Tetracycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Tetracycline
• Molecule Alteration: Expression; Up-regulation
• 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 tet38 expression. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain.

Clinical Trial Drug(s) 1 drug(s) in total

Cetrimide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Cetrimide
• Molecule Alteration: Expression; Up-regulation
• 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.

Investigative Drug(s) 2 drug(s) in total

Homidium bromide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Homidium bromide
• Molecule Alteration: Expression; Up-regulation
• 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.

Quinolones

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Quinolones
• Molecule Alteration: Expression; Up-regulation
• 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.

References

• Ref 1: 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.