抗生素诱导革兰阴性菌外膜囊泡产生及发挥生理作用的机制

Biogenesis and physiological functions of outer membrane vesicles triggered by antibiotics in gram-negative bacteria

外膜囊泡是革兰阴性菌分泌的一种球形纳米颗粒,由外膜及其所含成分组成,是细菌在外界压力条件下分泌的具有生理活性的特殊结构。外界压力如抗生素、缺氧等可触发细菌释放外膜囊泡,甚至在正常生长周期中,一些革兰阴性菌也会释放囊泡。外膜囊泡与细菌的多种生理过程相关,如应激反应、毒素传递、致病、细胞间通讯、免疫调节、基因水平转移及维持微生物群稳态等。在使用抗生素治疗过程中,尤其是当人体微生物群处于低剂量抗生素环境时,细菌会大量分泌外膜囊泡。在肠道中,外膜囊泡释放后会通过多种机制刺激肠道而引发多种炎症。本文综述了外膜囊泡的产生、结构及生理作用,提出抗生素治疗不但会破坏人体正常菌群而导致菌群失调,还会诱导细菌产生大量外膜囊泡而引发慢性炎症。噬菌体治疗不破坏正常菌群,特异性杀灭细菌时也不引起外膜囊泡的产生,因此开发使用噬菌体靶向治疗细菌感染将大大减少不良反应。

Outer membrane vesicles(OMVs)are spherical nanoparticles secreted by gram-negative bacteria,which are composed of outer membrane and bacterial components.These nanoparticles are secreted by bacteria under external pressure conditions,such as antibiotics,anaerobic and other adverse environments.These nanoparticles have special physiological activities in vivo.Some gram-negative bacteria secrete OMVs even during normal life cycle.OMVs play an important role in many physiological processes,such as response to stress,toxin transfer,pathogenicity,intercellular communication,immune regulation,gene transfer and maintenance of microbiota homeostasis,etc.When we use antibiotics,the microbiota is passively exposed to low doses of antibiotics,which results in the secretion of a large amount of OMVs.The release of OMVs will damage the intestine and induce various inflammations.The present paper reviewed the structure,production and physiological functions of OMVs and suggested that antibiotic exposure not only destroyed the normal flora but also led to the production of OMVs to induce chronic inflammations.Phage therapy does not destroy the normal flora,nor does it cause OMV releasing when killing the target bacteria.Therefore,the development of phage therapy targeting host bacteria will greatly reduce the side effects in treating infectious diseases.