2012年12月2日 訊 /生物谷BIOON/ --近日，刊登在國際雜誌mBio上的一篇研究報告中，來自丹麥哥本哈根大學的研究者揭示了針對含有陰性群體感應系統的金黃色葡萄球菌的抗生素的選擇。
金黃色葡萄球菌是人類機體中常見的一種共生菌，在某些條件下其可以轉化成致病菌，引發致命性的感染。為了精細控制細菌的毒力，金葡菌開發出了一套agr群體感應系統，其通過胞外效應分子RNAIII來調節毒力基因的表達。
這項研究中，研究者闡述了agr操縱子的存在可以增強金葡菌對於RNAIII的表達，進而影響細菌的毒力表達情況。未來研究中，研究者希望深入研究，暴露在不死劑量的抗生素環丙沙、莫匹羅星及利福平下，細菌是否可以通過誘導RNAIII的表達來增加agr給細菌所帶來的環境適應度及毒力。
研究者的研究結果闡述了為何從醫院金葡菌感染換種分離出的agr缺陷菌株比較頻繁，以及含有agr的金黃色葡萄球菌所表現出的對抗生素的適應性。
本文中，研究者Ingmer H說，我們發現了agr陰性的菌株相比agr陽性的菌株，在不死劑量抗生素的影響下所表現出較好的適應度，而且由於agr效應分子RNAIII的存在可以誘發agr陽性細胞出現適應度的缺失。這些結果可以幫助研究者解釋，為何臨床中總能夠分離得到agr缺失的金葡菌菌株，這就為研究者開發新型的抵禦金黃色葡萄球菌感染的療法提供了新的思路。（生物谷Bioon.com）
Antibiotic-Mediated Selection of Quorum-Sensing-Negative Staphylococcus aureus.
Paulander W, Nissen Varming A, Bæk KT, Haaber J, Frees D, Ingmer H.
Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. IMPORTANCE Staphylococcus aureus is the most frequently isolated pathogen in intensive care units and a common cause of nosocomial infections, resulting in a high degree of morbidity and mortality. Surprisingly, a large fraction (15 to 60%) of hospital-isolated S. aureus strains are agr defective and lack the main quorum-sensing-controlled virulence regulatory system. This is a problem, as agr-defective strains are associated with a mortality level in bacteremic infections and a probability of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression of the agr effector molecule RNAIII. These results offer an explanation of the frequent isolation of agr-defective S. aureus strains in hospitals and will influence how we treat S. aureus infections.