The Pseudomonas aeruginosa PrrF1 and PrrF2 small regulatory RNAs promote 2-alkyl-4- quinolone production through redundant regulation of the antR mRNA
JournalJournal of Bacteriology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractPseudomonas aeruginosa is an opportunistic Gram-negative pathogen that requires iron for growth and virulence. Under low-iron conditions, P. aeruginosa transcribes two highly identical (95%) small regulatory RNAs (sRNAs), PrrF1 and PrrF2, which are required for virulence in acute murine lung infection models. The PrrF sRNAs promote the production of 2-akyl-4(1H)-quinolone metabolites (AQs) that mediate a range of biological activities, including quorum sensing and polymicrobial interactions. Here, we show that the PrrF1 and PrrF2 sRNAs promote AQ production by redundantly inhibiting translation of antR, which encodes a transcriptional activator of the anthranilate degradation genes. A combination of genetic and biophysical analyses was used to define the sequence requirements for PrrF regulation of antR, demonstrating that the PrrF sRNAs interact with the antR 5= untranslated region (UTR) at sequences overlapping the translational start site of this mRNA. The P. aeruginosa Hfq protein interacted with UArich sequences in both PrrF sRNAs (Kd [dissociation constant] = 50 nM and 70 nM). Hfq bound with lower affinity to the antR mRNA (0.3 ?M), and PrrF was able to bind to antR mRNA in the absence of Hfq. Nevertheless, Hfq increased the rate of PrrF annealing to the antR UTR by 10-fold. These studies provide a mechanistic description of how the PrrF1 and PrrF2 sRNAs mediate virulence traits, such as AQ production, in P. aeruginosa. Copyright 2018 American Society for Microbiology.
SponsorsThis work was supported by NIH grants R01 AI123320 (to A.G.O.-S., S.A.W., and M.A.K.) and R01 GM120425 (to S.A.W.) and a University of Maryland School of Pharmacy Merit Award Fellowship (to L.D.)
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85045881384&doi=10.1128%2fJB.00704-17&partnerID=40&md5=4acb74292b6be8cde46e135680cd5ff2; http://hdl.handle.net/10713/9245
- The Pseudomonas aeruginosa PrrF Small RNAs Regulate Iron Homeostasis during Acute Murine Lung Infection.
- Authors: Reinhart AA, Nguyen AT, Brewer LK, Bevere J, Jones JW, Kane MA, Damron FH, Barbier M, Oglesby-Sherrouse AG
- Issue date: 2017 May
- The prrF-encoded small regulatory RNAs are required for iron homeostasis and virulence of Pseudomonas aeruginosa.
- Authors: Reinhart AA, Powell DA, Nguyen AT, O'Neill M, Djapgne L, Wilks A, Ernst RK, Oglesby-Sherrouse AG
- Issue date: 2015 Mar
- The influence of iron on Pseudomonas aeruginosa physiology: a regulatory link between iron and quorum sensing.
- Authors: Oglesby AG, Farrow JM 3rd, Lee JH, Tomaras AP, Greenberg EP, Pesci EC, Vasil ML
- Issue date: 2008 Jun 6
- The Pseudomonas aeruginosa CrcZ RNA interferes with Hfq-mediated riboregulation.
- Authors: Sonnleitner E, Prindl K, Bläsi U
- Issue date: 2017
- Static Growth Promotes PrrF and 2-Alkyl-4(1<i>H</i>)-Quinolone Regulation of Type VI Secretion Protein Expression in Pseudomonas aeruginosa.
- Authors: Brewer LK, Huang W, Hackert BJ, Kane MA, Oglesby AG
- Issue date: 2020 Nov 19