Disruption of Pseudomonas aeruginosa quorum sensing influences biofilm formation without affecting antibiotic tolerance.

IF 2.6 4区 生物学 Q3 MICROBIOLOGY
Elvina Smith, Andrew Matthews, Edze R Westra, Rafael Custodio
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引用次数: 0

Abstract

The opportunistic bacterial pathogen Pseudomonas aeruginosa is a leading cause of antimicrobial resistance-related deaths, and novel antimicrobial therapies are urgently required. P. aeruginosa infections are difficult to treat due to the bacterium's propensity to form biofilms, whereby cells aggregate to form a cooperative, protective structure. Autolysis, the self-killing of bacterial cells, and the bacterial cell-to-cell communication system, quorum sensing (QS), play essential roles in biofilm formation. Strains of P. aeruginosa that have lost the lasI/R QS system commonly develop in patients, and previous studies have characterized distinctive autolysis phenotypes in these strains. Yet, the underlying causes and implications of these autolysis phenotypes remain unknown. This study confirmed these autolysis phenotypes in the PA14 QS mutant strains, ΔlasI and ΔlasR, and investigated the consequences of QS loss and associated autolysis on biofilm formation and antibiotic susceptibility. QS mutants exhibited delayed biofilm formation but ultimately surpassed the wild-type (WT) in biofilm mass. However, the larger biofilm mass of the QS mutants was not reflected in higher live-cell numbers, indicating an altered biofilm structure. Nevertheless, QS mutant biofilms were not more susceptible to antibiotics than the WT. Artificial supplementation of ΔlasI with a QS signal molecule (autoinducer) restored the strain's QS system without the associated costs of QS, enabling ΔlasI to achieve higher pre-treatment and post-treatment live-cell numbers. Overall, the lack of QS functioning was not detrimental to biofilm antibiotic tolerance, though the artificial disruption of QS may reduce the advantages of QS mutants within in vivo mixed-strain populations. Much remains to be understood regarding the regulation and induction of the autolysis phenotypes observed in these strains, and future research to fully elucidate the control and consequences of autolysis may offer potential for novel antimicrobial therapies.

铜绿假单胞菌群体感应的破坏影响生物膜的形成而不影响抗生素的耐受性。
机会性细菌病原体铜绿假单胞菌是抗微生物药物耐药性相关死亡的主要原因,迫切需要新的抗微生物药物治疗。铜绿假单胞菌感染很难治疗,因为细菌倾向于形成生物膜,细胞聚集形成一个合作的保护结构。细菌细胞的自溶作用和细菌细胞间的通讯系统群体感应(quorum sensing, QS)在生物膜的形成中起着至关重要的作用。失去lasI/R QS系统的铜绿假单胞菌菌株通常在患者中发展,先前的研究已经在这些菌株中发现了独特的自溶表型。然而,这些自溶表型的潜在原因和含义仍然未知。本研究在PA14 QS突变菌株ΔlasI和ΔlasR中证实了这些自溶表型,并研究了QS丢失和相关的自溶对生物膜形成和抗生素敏感性的影响。QS突变体表现出生物膜形成延迟,但最终生物膜质量超过野生型(WT)。然而,更大的生物膜质量并没有反映在更高的活细胞数量上,这表明生物膜结构发生了改变。然而,QS突变体生物膜并不比WT更容易受到抗生素的影响。人工添加QS信号分子(自诱导剂)ΔlasI恢复了菌株的QS系统,而不需要QS的相关成本,使ΔlasI在处理前和处理后获得更高的活细胞数。总体而言,尽管人工破坏QS可能会降低QS突变体在体内混合菌株群体中的优势,但缺乏QS功能并不会损害生物膜的抗生素耐受性。在这些菌株中观察到的自溶表型的调节和诱导仍有待了解,未来的研究将充分阐明自溶的控制和后果,这可能为新的抗菌疗法提供潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microbiology-Sgm
Microbiology-Sgm 生物-微生物学
CiteScore
4.60
自引率
7.10%
发文量
132
审稿时长
3.0 months
期刊介绍: We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms. Topics include but are not limited to: Antimicrobials and antimicrobial resistance Bacteriology and parasitology Biochemistry and biophysics Biofilms and biological systems Biotechnology and bioremediation Cell biology and signalling Chemical biology Cross-disciplinary work Ecology and environmental microbiology Food microbiology Genetics Host–microbe interactions Microbial methods and techniques Microscopy and imaging Omics, including genomics, proteomics and metabolomics Physiology and metabolism Systems biology and synthetic biology The microbiome.
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