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(New page: ==Abstract== *Background **Staphylococcus aureus - human pathogen. Treatments are needed. Antimicrobial peptides potential antibiotic to MRSA. ***Such as Renalexin - fights against gram p...)
 
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==Background==
==Background==
*MRSA - major cause of mortality and mobility. Resistant strains to treatments continue to emerge. Global problem --> community-associated MRSA.
**Prevention and treatment is needed!
*Antimicrobial peptides (AMPs) - novel antibiotic --> could be developed to combat bacteria that is resistant (such as MRSA).
**Produces by all living creatures for defenses -- 880 have been described.
*Renalexin
**20 a.a. peptide (cationic)
**Possesses single intramolecular dispulphide bond --> forming heptapeptide ring at carboxyl terminus.
**Displays strong activity against Staphylococcus aureus (Gram-positive bacteria).
**Offers potential against staphylococcal infections (including MRSA).
*Need to understand antimicrobial action mechanisms to develop strategies.
*Antimicrobial inhibitory action can by studied by transcriptome and proteome profiling.
*Generation of protein and mRNA in response to antimicrobial stress are shown in certain cell functions and provide stress type imposed.
*Modeled pathway relationships for 95% of S. aureus MRSA-252 genes by integrating proteome and transcriptome profiling of bacteria that was drug-exposed w/ high-confidence functional association network.
**Approach showed 22 virulence factors and killing mechs. for renalexin along with cell wall effects.
**Evidence of VraRS two-component system in cationic peptide resistance.
*Drug target candidate - FtsH. Role of PhoU-mediated persister formation in S. aureus drug tolerance. 
==Results and Discussion==




Revision as of 15:32, 9 November 2011

Abstract

  • Background
    • Staphylococcus aureus - human pathogen. Treatments are needed. Antimicrobial peptides potential antibiotic to MRSA.
      • Such as Renalexin - fights against gram positive bacteria, S. aureus in particular.
    • Study of drug resistance and mode of action is important.
  • Results
    • Bayesian logistic regression - allows identification of renalexin response modules from MRSA-252 preteome and transcriptome profiling.
    • Relaxin displayed killing mechanisms & cell wall activity.
      • Gene disruption and osmotic fragility experiments supported cell wall effects.
    • 22 Virulence factors inferred --> VraRS two-component system & PhoU-mediated persister formation --> MRSA tolerance to cationic antimicrobial peptides.
  • Conclusions
    • Integrative approach to study drug resistance and their mode of action. Finds lead to development of trategies against Staphylococcus aureus (MRSA in particular)

Background

  • MRSA - major cause of mortality and mobility. Resistant strains to treatments continue to emerge. Global problem --> community-associated MRSA.
    • Prevention and treatment is needed!
  • Antimicrobial peptides (AMPs) - novel antibiotic --> could be developed to combat bacteria that is resistant (such as MRSA).
    • Produces by all living creatures for defenses -- 880 have been described.
  • Renalexin
    • 20 a.a. peptide (cationic)
    • Possesses single intramolecular dispulphide bond --> forming heptapeptide ring at carboxyl terminus.
    • Displays strong activity against Staphylococcus aureus (Gram-positive bacteria).
    • Offers potential against staphylococcal infections (including MRSA).
  • Need to understand antimicrobial action mechanisms to develop strategies.
  • Antimicrobial inhibitory action can by studied by transcriptome and proteome profiling.
  • Generation of protein and mRNA in response to antimicrobial stress are shown in certain cell functions and provide stress type imposed.
  • Modeled pathway relationships for 95% of S. aureus MRSA-252 genes by integrating proteome and transcriptome profiling of bacteria that was drug-exposed w/ high-confidence functional association network.
    • Approach showed 22 virulence factors and killing mechs. for renalexin along with cell wall effects.
    • Evidence of VraRS two-component system in cationic peptide resistance.
  • Drug target candidate - FtsH. Role of PhoU-mediated persister formation in S. aureus drug tolerance.

Results and Discussion

Links

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