Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin
Accessory gene regulator (agr) locus in geographically diverse Staphylococcus aureus isolates with reduced susceptibility to vancomycin
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DOI：
10.1128/aac.46.5.1492-1502.2002
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发表时间：
2002-05-01
影响因子：
4.9
通讯作者：
Gold, HS
中科院分区：
文献类型：
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作者：
Sakoulas, G;Eliopoulos, GM;Gold, HS
大多数感染糖肽中间水平耐药金黄色葡萄球菌（GISA）起源于生物医学设备，这表明这些菌株产生生物膜的能力可能增加。辅助基因调节子（agr）功能丧失。已经提出金黄色葡萄球菌赋予增强的结合聚苯乙烯的能力。我们研究了GISA、异源GISA和相关糖肽敏感金黄色葡萄球菌分离株中的agr。来自不同地理来源的所有GISA菌株都属于Agr组II。所有GISA菌株都有agr功能缺陷，如它们不能产生δ-溶血素所证明的。Hetero-GISA分离株A5940在agrA中显示无义突变，而在来自同一患者的脉冲场凝胶电泳无法区分万古霉素敏感分离株中不存在该突变。在几种临床GISA和异源GISA分离株中观察到各种其他agr点突变。实验室产生的agr无效菌株表现出一个小的，但可重复的增加，在体外生长后，在万古霉素的亚抑制浓度的万古霉素的异源耐药性。这是没有看到在等基因agr组II亲本菌株，其中agr是完整的。与亲本菌株相比，万古霉素的体外杀菌活性在agr无效菌株中减弱。这些发现意味着受损的agr功能对临床分离的S.金黄色葡萄球菌对万古霉素的异质耐药性的发展，可能通过万古霉素耐受性的发展。
The majority of infections with glycopeptide intermediate-level resistant Staphylococcus aureus (GISA) originate in biomedical devices, suggesting a possible increased ability of these strains to produce biofilm. Loss of function of the accessory gene regulator (agr) of S. aureus has been suggested to confer an enhanced ability to bind to polystyrene. We studied agr in GISA, hetero-GISA, and related glycopeptide-susceptible S, aureus isolates. All GISA strains from diverse geographic origins belong to agr group II. All GISA strains were defective in agr function, as demonstrated by their inability to produce delta-hemolysin. Hetero-GISA isolate A5940 demonstrated a nonsense mutation in agrA that was not present in a pulsed-field gel electrophoresis-indistinguishable vancomycin-susceptible isolate from the same patient. Various other agr point mutations were noted in several clinical GISA and hetero-GISA isolates. A laboratory-generated agr-null strain demonstrated a small but reproducible increase in vancomycin heteroresistance after growth in vitro in subinhibitory concentrations of vancomycin. This was not seen in the isogenic agr group II parent strain in which agr was intact. The in vitro bactericidal activity of vancomycin was attenuated in the agr-null strain compared to the parent strain. These findings imply that compromised agr function is advantageous to clinical isolates of S. aureus toward the development of vancomycin heteroresistance, perhaps through the development of vancomycin tolerance.