Abstract
Pseudomonas aeruginosa is an opportunistic pathogen commonly infecting immunocompromised patients with diseases like cystic fibrosis (CF) and cancers and has high rates of recurrence and mortality. The treatment efficacy can be significantly worsened by the multidrug resistance (MDR) of P. aeruginosa, and there is increasing evidence showing that it is easy for this pathogen to develop MDR. Here, we identified a gene cluster, pltZ-pltIJKNOP, which was originally assumed to be involved in the biosynthesis of an antimicrobial pyoluteorin, significantly contributing to the antibiotic resistance of P. aeruginosa ATCC 27853. Moreover, the TetR family regulator PltZ binds to a semi-palindromic sequence in the promoter region of the pltIJKNOP operon and recognizes the antimicrobial 2,4-diacetylphloroglucinol (2,4-DAPG), which in turn induces the expression of the pltIJKNOP operon. Using quantitative proteomics method, it was indicated that the regulator PltZ also plays an important role in maintaining metabolic hemostasis by regulating the transporting systems of amino acids, glucose, metal ions, and bacteriocins.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen that infects a wide range of hosts, including plants and animals (Rahme et al, 1995)
P. aeruginosa M18, PACS171b, and PACS88A were shown to produce pyoluteorin, genomic analysis of P. aeruginosa LESB58, a highly virulent clinical strain isolated from cystic fibrosis (CF) patients, revealed that the pltB gene within the plt biosynthetic gene cluster pltRM-pltLABCDEFG had a 5-bp deletion resulting in a truncated PltB protein and a defect in pyoluteorin biosynthesis (Winstanley et al, 2009)
As our proteomic data revealed that PltZ influences multiple physiological processes of P. aeruginosa ATCC 27853, especially the transporting systems of amino acids, glucose, metal ions, and bacteriocins, it is probable that sub-inhibitory concentrations of 2,4-DAPG could serve as a signaling molecule modulating bacterial physiology through allosteric regulation of PltZ
Summary
Pseudomonas aeruginosa is an opportunistic pathogen that infects a wide range of hosts, including plants and animals (Rahme et al, 1995). It was reported to infect lettuce (Paine and Branfoot, 1924; Elrod and Braun, 1942), sugarcane (Desai, 1935), and tobacco (Yu et al, 2008). The treatment efficacy can be significantly worsened by the multidrug resistance (MDR) of P. aeruginosa, and there is increasing evidence showing that it is easy for this pathogen to develop MDR by acquiring transferable resistance genes. The genomes of P. aeruginosa encode several resistance–nodulation–cell division (RND)-type efflux systems, four of which, i.e., MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM, are characterized to be essential for MDR (Poole, 2011). Understanding the MDR mechanism is of primary priority for the development of new therapies for treating P. aeruginosa infection
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