α-毒素有助于金黄色葡萄球菌伤口分离株形成生物膜。

Alpha-Toxin Contributes to Biofilm Formation among Staphylococcus aureus Wound Isolates.

机构信息

Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.

Heath Care Business Group, 3M, St. Paul, MN 55144, USA.

出版信息

Toxins (Basel). 2018 Apr 16;10(4):157. doi: 10.3390/toxins10040157.

Biofilms complicate treatment of (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production. We also investigated the effect of an anti-AT monoclonal antibody (MEDI4893*) on ex vivo biofilm formation by methicillin-resistant SA (USA 300 LAC) and tested whether purified AT rescued the biofilm defect of mutant SA strains. The predominant PFGE/ST combinations were USA100/ST5 (50%) and USA300/ST8 (33%) for methicillin-resistant SA (MRSA, = 18), and USA200/ST30 (20%) for methicillin-susceptible SA (MSSA, = 20). Ex vivo AT production correlated significantly with ex vivo SA wound isolate biofilm formation. Anti-alpha-toxin monoclonal antibody (MEDI4893*) prevented ex vivo biofilm formation by MRSA USA300 strain LAC. Wild-type AT rescued the ex vivo biofilm defect of non-AT producing SA strains. These findings provide evidence that AT plays a role in SA biofilm formation on epithelial surfaces and suggest that neutralization of AT may be useful in preventing and treating SA infections.

生物膜使（SA）伤口感染的治疗变得复杂。此前，我们确定了 alpha 毒素（AT）促进粘膜组织上 SA 生物膜的形成。因此，我们评估了 SA 伤口分离株的 AT 产生和上皮生物膜形成，并评估了 AT 在生物膜形成中的作用。38 个伤口分离株通过脉冲场凝胶电泳（PFGE）、多位点序列分型（ST）和分型进行分子分型。我们测量了这些 SA 分离株在体外和体内的生物膜形成，并定量了体内 AT 的产生。我们还研究了抗 AT 单克隆抗体（MEDI4893*）对耐甲氧西林 SA（USA 300 LAC）体外生物膜形成的影响，并测试了纯化的 AT 是否可以挽救突变 SA 菌株的生物膜缺陷。主要的 PFGE/ST 组合为耐甲氧西林 SA（MRSA， = 18）的 USA100/ST5（50%）和 USA300/ST8（33%），以及甲氧西林敏感 SA（MSSA， = 20）的 USA200/ST30（20%）。体外 AT 产生与体外 SA 伤口分离株生物膜形成显著相关。抗 alpha 毒素单克隆抗体（MEDI4893*）可防止 MRSA USA300 株 LAC 的体外生物膜形成。野生型 AT 挽救了非 AT 产生的 SA 菌株的体外生物膜缺陷。这些发现提供了证据表明 AT 在 SA 生物膜形成上皮表面上起作用，并表明中和 AT 可能有助于预防和治疗 SA 感染。