The QseEF Two-Component System-GlmY Small RNA Regulatory Pathway Controls Swarming in Uropathogenic Proteus mirabilis

Abstract

Bacterial sensing of environmental signals through the two-component system (TCS) plays a key role in modulating virulence. In the search for the host hormone-sensing TCS, we identified a conserved qseEGF locus following glmY, a small RNA (sRNA) gene in uropathogenic Proteus mirabilis. Genes of glmY-qseE-qseG-qseF constitute an operon, and QseF binding sites were found in the glmY promoter region. Deletion of glmY or qseF resulted in reduced swarming motility and swarming-related phenotypes relative to the wild-type and the respective complemented strains. The qseF mutant had decreased glmYqseEGF promoter activity. Both glmY and qseF mutants exhibited decreased flhDC promoter activity and mRNA level, while increased rcsB mRNA level was observed in both mutants. Prediction by TargetRNA2 revealed cheA as the target of GlmY. Then, construction of the translational fusions containing various lengths of cheA 5′UTR for reporter assay and site-directed mutagenesis were performed to investigate the cheA-GlmY interaction in cheA activation. Notably, loss of glmY reduced the cheA mRNA level, and urea could inhibit swarming in a QseF-dependent manner. Altogether, this is the first report elucidating the underlying mechanisms for modulation of swarming motility by a QseEF-regulated sRNA GlmY, involving expression of cheA, rcsB and flhDC in uropathogenic P. mirabilis.

In Vivo Role of Two-Component Regulatory Systems in Models of Urinary Tract Infections

“…Another recent paper has also highlighted the role played by the QseEF TCS in modulating swarming motility. In general, the activated sensor kinase QseE determines the phosphorylation of the regulator QseF that, in turn, activates the expression of GlmY together with CheA and RcsB, two antagonist regulators of flagellum production [ 245 ]. A recent case report has described evidence of acquisition of resistance to imipenem and amikacin in a Proteus mirabilis clinical isolate, not previously showing this feature.…”

Into the understanding the multicellular lifestyle of Proteus mirabilis on solid surfaces

“…Meanwhile, the most recent study revealed that the QseEF twocomponent system-GlmY Small RNA (sRNA) regulatory pathway controls the P. mirabilis swarming. This is the first report in which a pathway mediated by a two-component system through an sRNA was disclosed to be involved in swarming migration (Lin et al, 2022). This observation is intrigue given the fact that in silico study reported the detection of 14 sRNA candidates, conserved in the orthologous regions of P. mirabilis, which biological role remains unexplained (KishanRaj et al, 2018).…”

Transcriptional Regulation and Its Misregulation in Human Diseases

“…In this Special Issue, a total of 18 excellent and interesting papers [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], consisting of 13 original research studies [3][4][5][6][10][11][12][14][15][16][18][19][20], as well as five reviews, are published [7][8][9]13,17]. They cover many subjects of transcriptional regulation, including studies on cis-regulatory elements, transcription factors (TF), chromatin regulators, and ncRNAs.…”

“…Generally, bacteria utilize the two-component system (TCS) method, such as QseEF, to control gene expression in response to rapid environmental changes. Of note, many recognized mechanisms function through the post-transcriptional control of small non-coding RNAs (sRNAs), and their identification is rapidly increasing in number and variety in the context of bacteria regulatory functions [19]. Interestingly, in a study in the present Special Issue, the authors identified the QseEF homologue of Proteus mirabilis, an Important pathogen of the urinary tract, principally in patients with indwelling urinary catheters, and they found it is involved in the modulation of swarming motility through the sRNA GlmY.…”

“…This is the first study investigating a pathway mediated by a two-component system through a sRNA as an underlying pathogenetic mechanism of Proteus mirabilis swarming migration, during which expression of several virulence genes is increased. Since it is assumed that P. mirabilis swarming up catheters is primed to infect the urinary tract, clarifying the swarming mechanisms could provide new approaches in the development of intervention strategies and facilitate the discovery of novel therapeutics [19].…”