Abstract：
Bacteriophages (hereafter \"phages\") are ubiquitous predators of bacteria in the natural world, but interest is growing in their development into antibacterial therapy as complement or replacement for antibiotics. However, bacteria have evolved a huge variety of antiphage defense systems allowing them to resist phage lysis to a greater or lesser extent. In addition to dedicated phage defense systems, some aspects of the general stress response also impact phage susceptibility, but the details of this are not well known. In order to elucidate these factors in the opportunistic pathogen Pseudomonas aeruginosa, we used the laboratory-conditioned strain PAO1 as host for phage infection experiments as it is naturally poor in dedicated phage defense systems. Screening by transposon insertion sequencing indicated that the uncharacterized operon PA3040-PA3042 was potentially associated with resistance to lytic phages. However, we found that its primary role appeared to be in regulating biofilm formation, particularly in a clinical isolate of P. aeruginosa in which it also altered tobramycin resistance. Its expression was highly growth-phase dependent and responsive to phage infection and cell envelope stress. Our results suggest that this operon may be a cryptic but important locus for P. aeruginosa stress tolerance.
OBJECTIVE: An important category of bacterial stress response systems is bacteriophage defense, where systems are triggered by bacteriophage infection and activate a response which may either destroy the phage genome or destroy the infected cell so that the rest of the population survives. In some bacteria, the cell envelope stress response is activated by bacteriophage infection, but it is unknown whether this contributes to the survival of the infection. We have found that a conserved uncharacterized operon (PA3040-PA3042) of the cell envelope stress regulon in Pseudomonas aeruginosa, which has very few dedicated phage defense systems, responds to phage infection and stationary phase as well as envelope stress and is important for growth and biofilm formation in a clinical isolate of P. aeruginosa, even in the absence of phages. As homologs of these genes are found in other bacteria, they may be a novel component of the general stress response.
OBJECTIVE: An important category of bacterial stress response systems is bacteriophage defense, where systems are triggered by bacteriophage infection and activate a response which may either destroy the phage genome or destroy the infected cell so that the rest of the population survives. In some bacteria, the cell envelope stress response is activated by bacteriophage infection, but it is unknown whether this contributes to the survival of the infection. We have found that a conserved uncharacterized operon (PA3040-PA3042) of the cell envelope stress regulon in Pseudomonas aeruginosa, which has very few dedicated phage defense systems, responds to phage infection and stationary phase as well as envelope stress and is important for growth and biofilm formation in a clinical isolate of P. aeruginosa, even in the absence of phages. As homologs of these genes are found in other bacteria, they may be a novel component of the general stress response.
摘要：
噬菌体（以下简称“噬菌体”）是自然界中普遍存在的细菌捕食者，但是人们对它们发展成抗菌疗法作为抗生素的补充或替代越来越感兴趣。然而,细菌已经进化出各种各样的抗噬菌体防御系统，使它们能够或多或少地抵抗噬菌体裂解。除了专门的噬菌体防御系统,一般应激反应的某些方面也会影响噬菌体的易感性，但是细节并不为人所知。为了阐明机会致病菌铜绿假单胞菌中的这些因素,我们使用实验室条件菌株PAO1作为噬菌体感染实验的宿主，因为它在专用噬菌体防御系统中自然较差。通过转座子插入测序进行的筛选表明，未表征的操纵子PA3040-PA3042可能与对裂解噬菌体的抗性有关。然而,我们发现它的主要作用似乎是调节生物膜的形成，特别是在铜绿假单胞菌的临床分离物中，它也改变了妥布霉素的抗性。它的表达是高度生长阶段依赖性的，并且对噬菌体感染和细胞包膜胁迫具有响应性。我们的结果表明，该操纵子可能是铜绿假单胞菌胁迫耐受性的隐秘但重要的基因座。
目的：细菌应激反应系统的一个重要类别是噬菌体防御，其中系统由噬菌体感染触发，并激活反应，该反应可能会破坏噬菌体基因组或破坏受感染的细胞，从而使其余群体存活。在一些细菌中，细胞包膜应激反应被噬菌体感染激活，但尚不清楚这是否有助于感染的生存。我们已经发现铜绿假单胞菌中细胞包膜应激调节子的保守的未表征操纵子（PA3040-PA3042），很少有专门的噬菌体防御系统，对噬菌体感染和稳定期以及包膜应激有反应，对铜绿假单胞菌临床分离株的生长和生物膜形成很重要，即使没有噬菌体。由于这些基因的同源物在其他细菌中发现，它们可能是一般应激反应的新组成部分。
目的：细菌应激反应系统的一个重要类别是噬菌体防御，其中系统由噬菌体感染触发，并激活反应，该反应可能会破坏噬菌体基因组或破坏受感染的细胞，从而使其余群体存活。在一些细菌中，细胞包膜应激反应被噬菌体感染激活，但尚不清楚这是否有助于感染的生存。我们已经发现铜绿假单胞菌中细胞包膜应激调节子的保守的未表征操纵子（PA3040-PA3042），很少有专门的噬菌体防御系统，对噬菌体感染和稳定期以及包膜应激有反应，对铜绿假单胞菌临床分离株的生长和生物膜形成很重要，即使没有噬菌体。由于这些基因的同源物在其他细菌中发现，它们可能是一般应激反应的新组成部分。
