Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa
Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa
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DOI：
10.1099/jmm.0.45617-0
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发表时间：
2004-09-01
影响因子：
3
通讯作者：
Hamood, AN
中科院分区：
文献类型：
--
作者：
Schaber, JA;Carty, NL;Hamood, AN
铜绿假单胞菌产生多种毒力因子，引起不同类型的感染。以前的临床研究发现，铜绿假单胞菌缺乏个体毒力因子。然而，同时失去几个毒力因子对铜绿假单胞菌体内毒力的影响还不完全清楚。铜绿假单胞菌的细胞间通讯系统或群体感应(QS)控制着几种毒力因子的产生。利用构建的qs突变体进行的动物研究表明，OS系统的丧失严重影响了铜绿假单胞菌的毒力。在这项研究中，我们试图确定QS系统中的缺陷是否会损害铜绿假单胞菌在人类中建立感染的能力。我们通过对200株尿路、下呼吸道和伤口感染患者分离的菌株进行筛选，鉴定出5株QS缺陷菌株。这些菌株缺乏LasB和LASA活性，不产生或产生很低水平的自身诱导剂N-(3-氧代十二烷基)高丝氨酸内酯和N-丁酰高丝氨酸内酯。聚合酶链式反应分析表明，3株分离物含有全部4个qS基因(LasI、LasR、rhII和rhIR)，2株同时缺失LasR和rhIR基因。我们还检测了这五个分离株的其他毒力因子。这些分离物产生不同程度的外毒素A，并且，除了一个例外，缺乏绿青素的产生。一个菌株产生III型分泌系统(TTSS)效应蛋白EXOS和ExoT，两个菌株只产生ExoT，两个菌株不产生TTSS蛋白。这些菌株在非生物表面产生弱到中等的生物膜。对患者数据的分析显示，其中两个分离株代表一个菌株，该菌株在1个月的间隔内从同一患者身上分离了两次。1株QS缺陷型临床分离株(CI-1)缺乏所有毒力因子，生物被膜较弱。这些结果表明，自然产生的QS缺陷的铜绿假单胞菌菌株确实存在，并能够引起感染；除了已知的毒力因素外，其他因素可能有助于某些菌株，如CI-1，建立感染的能力。
Pseudomonas aeruginosa produces multiple virulence factors and causes different types of infections. Previous clinical studies identified P. aeruginosa isolates that lack individual virulence factors. However, the impact of losing several virulence factors simultaneously on the in vivo virulence of P. aeruginosa is not completely understood. The P. aeruginosa cell-to-cell communication system, or quorum sensing (QS), controls the production of several virulence factors. Animal studies using constructed QS mutants indicated that loss of the OS system severely impacts the virulence of P. aeruginosa. In this study, we tried to determine if deficiency within the QS system compromises the ability of P. aeruginosa to establish infections in humans. We have identified five QS-deficient strains through screening 200 isolates from patients with urinary tract, lower respiratory tract and wound infections. These strains lacked LasB and LasA activities and produced either no or very low levels of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone. PCR analysis revealed that three isolates contained all four QS genes (lasI, lasR, rhII and rhIR) while two isolates lacked both the lasR and rhIR genes. We also examined the five isolates for other virulence factors. The isolates produced variable levels of exotoxin A and, with one exception, were deficient in pyocyanin production. One isolate produced the type III secretion system (TTSS) effector proteins ExoS and ExoT, two isolates produced ExoT only and two isolates produced no TTSS proteins. The isolates produced weak to moderate biofilms on abiotic surfaces. Analysis of the patients' data revealed that two of the isolates represented a single strain that was isolated twice from the same patient within a 1 month interval. One QS-deficient clinical isolate (CI-1) lacked all tested virulence factors and produced a weak biofilm. These results suggest that naturally occurring QS-deficient strains of P. aeruginosa do occur and are capable of causing infections; and, that besides the known virulence factors, additional factors may contribute to the ability of certain strains such as CI-1 to establish an infection.