Kiran Madanahally D, Balaban Naomi
Department of Biological Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA.
Int J Artif Organs. 2009 Sep;32(9):592-9. doi: 10.1177/039139880903200908.
Staphylococci are common pathogens of implant-related infections. RIP is a heptapeptide (YSPWTNF-NH2 ) that was shown to be very effective in preventing and treating antibiotic-resistant staphylococcal infections, in healing polymicrobial wounds, and in enhancing the effect of commonly used antibiotics. How the peptide negatively affects the survival of the bacteria in the host is not yet known. In staphylococci, RIP was shown to suppress toxin production by inhibiting the expression of agr and production of RNAIII. RIP was also shown to suppress the phosphorylation of TRAP (target of RNAIII-activating peptide), whose function was not clear. Here we show that mutant S. aureus TRAP- cells were more sensitive to oxidative stress and had higher rates of spontaneous and adaptive (agr) mutations. Furthermore, recombinant TRAP protected DNA from oxidative damage caused by hydroxyl radicals. Put together, these results suggest that TRAP is involved in DNA protection from stress. RIP may thus suppress pathogenesis through multiple independent molecular mechanisms involving both suppression of virulence and suppression of stress response.
葡萄球菌是植入物相关感染的常见病原体。RIP是一种七肽（YSPWTNF-NH2），已证明其在预防和治疗耐抗生素葡萄球菌感染、愈合混合微生物伤口以及增强常用抗生素的效果方面非常有效。该肽如何对宿主体内细菌的存活产生负面影响尚不清楚。在葡萄球菌中，RIP已证明通过抑制agr的表达和RNAIII的产生来抑制毒素产生。RIP还证明可抑制TRAP（RNAIII激活肽的靶标）的磷酸化，其功能尚不清楚。在这里我们表明，金黄色葡萄球菌TRAP-突变细胞对氧化应激更敏感，并且自发和适应性（agr）突变率更高。此外，重组TRAP可保护DNA免受羟基自由基引起的氧化损伤。综合来看，这些结果表明TRAP参与了DNA的应激保护。因此，RIP可能通过多种独立的分子机制抑制发病机制，这些机制包括抑制毒力和抑制应激反应。
