Specific and Global RNA Regulators in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa (Pae) is an opportunistic pathogen showing a high intrinsic resistance to a wide variety of antibiotics. It causes nosocomial infections that are particularly detrimental to immunocompromised individuals and to patients suffering from cystic fibrosis. We provide a snapshot on regulatory RNAs of Pae that impact on metabolism, pathogenicity and antibiotic susceptibility. Different experimental approaches such as in silico predictions, co-purification with the RNA chaperone Hfq as well as high-throughput RNA sequencing identified several hundreds of regulatory RNA candidates in Pae. Notwithstanding, using in vitro and in vivo assays, the function of only a few has been revealed. Here, we focus on well-characterized small base-pairing RNAs, regulating specific target genes as well as on larger protein-binding RNAs that sequester and thereby modulate the activity of translational repressors. As the latter impact large gene networks governing metabolism, acute or chronic infections, these protein-binding RNAs in conjunction with their cognate proteins are regarded as global post-transcriptional regulators.

Characterization of the Achromobacter xylosoxidans Type VI Secretion System and Its Implication in Cystic Fibrosis

“…A. xylosoxidans shares common traits with other human pathogens in its capacity to respond and adapt to a human host, optimizing its long-term survival potential. P. aeruginosa has developed an intricate regulation network to adapt and to balance metabolism, virulence factors, and other cellular processes in response to its immediate environment ( Pusic et al., 2021 ). Future works are needed to determine whether such adaptation occurs also in A. xylosoxidans , as suggested by our work, and to determine the players and the network they participate in.…”

Conquering the host: Bordetella spp. and Pseudomonas aeruginosa molecular regulators in lung infection

“…In P. aeruginosa , more than half of the characterized sRNAs are dependent on or mediated by the Hfq chaperone, which we will discuss later, and or two component systems such as GacAS ( Pusic et al, 2021 ). Examples of sRNAs include, RsmY and RsmZ, both of which are involved in the switch from the motile to the sessile mode of life, modulate the expression of the T3SS and type 6 secretion system (T6SS) ( Mikkelsen et al, 2011 ) and, thus, the transition from acute to persistent infection ( Li et al, 2017 ).…”

Polymorphic ribonucleoprotein folding as a basis for translational regulation

“…One system depends on the CsrA-like Rsm proteins, which act as translational repressors and engage GGA motifs in the Shine-Dalgarno sequence of target mRNAs that are often exposed in loops of stem-loop structures (Dubey et al, 2005;Schubert et al, 2007, Goodman et al, 2016Holmqvist et al, 2016;Romero et al, 2018;Gebhardt et al, 2020). The other system depends on the RNA chaperone Hfq, a member of the widely occurring Lsm/Sm protein family, which facilitates the actions of small regulatory RNAs (sRNAs; Pusic et al, 2021), and can act as a translational repressor of target mRNAs (Sonnleitner & Bläsi, 2014;Sonnleitner et al, 2018;Kambara et al, 2018;Gebhardt et al, 2020;. Through these activities, Hfq contributes to the coordination of stress responses (Lu et al, 2016), metabolism (Sonnleitner & Bläsi, 2014), quorum sensing (Sonnleitner et al, 2006;Yang et al, 2015), virulence (Sonnleitner et al, 2003), and affects complex processes such as biofilm formation and the antibiotic susceptibility (Fernàndez et al, 2016;Pusic et al, 2016, Zhang et al 2017Pusic et al, 2018;Sonnleitner et al, 2020).…”