PBP3 inhibition elicits adaptive responses in Pseudomonas aeruginosa
PBP3 inhibition elicits adaptive responses in Pseudomonas aeruginosa
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DOI：
10.1111/j.1365-2958.2006.05366.x
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Martin, Soledad
中科院分区：
文献类型：
--
作者：
Blazquez, Jesus;Gomez-Gomez, Jose-Maria;Martin, Soledad
适应性进化取决于生物种群的遗传变异性和选择更适应的基因型。然而，为了选择最合适的变体，它们必须在新的条件下存活足够长的时间。细菌在自然界中经常暴露于不同类型的压力，包括抗生素。我们分析了条件致病菌铜绿假单胞菌在不同浓度和时间下对头孢他啶（一种PBP 3抑制剂）的反应的全球表达谱。PBP 3抑制对大量基因的转录产生全局影响。从适应性的角度来看，值得注意的是几个SOS基因的诱导，以及适应，保护和抗生素抗性基因。有趣的是，先前描述为SOS调节的绿脓菌素基因的转录在PBP 3抑制后被抑制。SOS诱导剂环丙沙星产生绿脓菌素的转录诱导。我们的研究结果表明：（i）由这两种抗生素处理引起的SOS反应仅引起部分重叠的转录谱;（ii）PBP 3和DNA-促旋酶抑制对绿脓菌素基因的转录产生相反的影响。因此，头孢他啶降低环丙沙星毒性;（iii）易错DNA聚合酶DinB由PBP 3抑制诱导，但不由DNA旋转酶抑制诱导;（iv）PBP 3抑制引起诱发突变;（v）头孢他啶上调几个抗肿瘤抗性和适应基因;和（vi）以前认为是致命的头孢他啶浓度不是，因为用头孢他啶处理的大多数细胞保持存活并恢复其形成集落的能力。因此，在这项工作中表现出的转录变化很可能是适应性相关的生存细胞。
Adaptive evolution depends on both the genetic variability in a population of organisms and the selection of the better adapted genotypes. However, for the fittest variants to be selected they must survive over a sufficient period under the new conditions. Bacteria are often exposed to different types of stress in nature, including antibiotics. We analysed the global expression profiles of the opportunistic pathogen Pseudomonas aeruginosa in response to ceftazidime, a PBP3 inhibitor, at different concentrations and times. PBP3 inhibition exerts a global impact on the transcription of a large number of genes. From an adaptive perspective, it is noteworthy the induction of several SOS genes, as well as adaptation, protection and antibiotic resistance genes. Intriguingly, transcription of pyocin genes, previously described as SOS-regulated, was repressed upon PBP3 inhibition. Ciprofloxacin, an SOS inducer, produced transcriptional induction of pyocins. Our results indicate that: (i) the SOS responses resulting from treatments with these two antibiotics cause only partially overlapping transcription profiles; (ii) PBP3 and DNA-gyrase inhibition produce opposite effects on transcription of pyocin genes. Consequently, ceftazidime decreases ciprofloxacin toxicity; (iii) error-prone DNA-polymerase DinB is induced by PBP3 inhibition but not by DNA-gyrase inhibition; (iv) PBP3 inhibition causes induced mutagenesis; (v) ceftazidime upregulates several antibiotic-resistance and adaptation genes; and (vi) ceftazidime concentrations thought previously to be lethal are not, as most cells treated with ceftazidime remain alive and recover their capacity to form colonies. Thus, transcriptional changes demonstrated in this work are likely to be adaptively relevant to cells that survive.