Molecular mechanisms of RIP, an effective inhibitor of chronic infections.
Non-healing bacterial infections are often associated with the formation of a biofilm, where bacteria are more resistant to conventional treatment modalities and to host immune responses. We show here that RNAIII inhibiting peptide (RIP), a linear heptapeptide, is very effective in treating severe polymicrobial infections, including drug-resistant staphylococci like MRSA. By functional genomics studies (microarray analysis) on Staphylococcus aureus, we show here that RIP downregulates the expression of genes involved in biofilm formation and toxin production, and upregulates genes involved in stress response. This pattern of gene regulation may explain why RIP has been so effective in treating severe infections and hopefully through the addition of RIP to existing protocols, a new way of tackling chronic persistent infections will be established.
Tufts University, Cummings School of Veterinary Medicine, Department of Biomedical Sciences, North Grafton, MA, USA.
Florencia
F
Lopez-Leban
Madanahally Divakar
MD
Kiran
Randall
R
Wolcott
Naomi
N
Balaban
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics; D018441:Biofilms / Q000187:drug effects*; D002908:Chronic Disease; D017719:Diabetic Foot / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004359:Drug Therapy, Combination; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D013312:Stress, Physiological / Q000235:genetics; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics; D016896:Treatment Outcome; D037521:Virulence Factors / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
C095698:Agr protein, Staphylococcus aureus; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D009842:Oligopeptides; C111711:RNAIII inhibiting peptide; D015534:Trans-Activators; D037521:Virulence Factors