<scp>ppGpp</scp> mediates the growth phase‐dependent regulation of <i>agn43</i>, a phase variable gene, by stimulating its promoter activity

Cabrer-Panes, Juan David; Fernández-Coll, Llorenç; Fernández-Vázquez, Jorge; Gaviria-Cantin, Tania; Mouali, Youssef El; Åberg, Anna; Balsalobre, Carlos

doi:10.1111/1758-2229.12860

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…In this case, the levels of (p)ppGpp will spike after invasion due to the lack of nutrients or due to oxidative stress and acidic pH inside macrophages ( Fitzsimmons et al, 2018 , 2020 ). Even commensal E. coli expresses factors essential for biofilm and colonization of surfaces such as fimbria, flagella, or antigen 43, just after the peak of (p)ppGpp during stationary phase ( Aberg et al, 2008 , 2009 ; Cabrer-Panes et al, 2020 ).…”

Section: Basal Levels Of (P)ppgpp and Pathogenicitymentioning

confidence: 99%

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

Fernández-Coll

Cashel

2020

Front. Microbiol.

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Two (p)ppGpp nucleotide analogs, sometimes abbreviated simply as ppGpp, are widespread in bacteria and plants. Their name alarmone reflects a view of their function as intracellular hormone-like protective alarms that can increase a 100-fold when sensing any of an array of physical or nutritional dangers, such as abrupt starvation, that trigger lifesaving adjustments of global gene expression and physiology. The diversity of mechanisms for stress-specific adjustments of this sort is large and further compounded by almost infinite microbial diversity. The central question raised by this review is whether the small basal levels of (p)ppGpp functioning during balanced growth serve very different roles than alarmone-like functions. Recent discoveries that abrupt amino acid starvation of Escherichia coli , accompanied by very high levels of ppGpp, occasion surprising instabilities of transfer RNA (tRNA), ribosomal RNA (rRNA), and ribosomes raises new questions. Is this destabilization, a mode of regulation linearly related to (p)ppGpp over the entire continuum of (p)ppGpp levels, including balanced growth? Are regulatory mechanisms exerted by basal (p)ppGpp levels fundamentally different than for high levels? There is evidence from studies of other organisms suggesting special regulatory features of basal levels compared to burst of (p)ppGpp. Those differences seem to be important even during bacterial infection, suggesting that unbalancing the basal levels of (p)ppGpp may become a future antibacterial treatment. A simile for this possible functional duality is that (p)ppGpp acts like a car’s brake, able to stop to avoid crashes as well as to slow down to drive safely.

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Section: Basal Levels Of (P)ppgpp and Pathogenicitymentioning

confidence: 99%

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

Fernández-Coll

Cashel

2020

Front. Microbiol.

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“…Indeed, (p)ppGpp regulates positively or negatively transcription initiation from specific promoters by binding directly to RNA polymerase (RNAP) at two sites [34,35]. In these (p)ppGpp regulated promoters, a discriminator region (region between the conserved -10 promoter element and the transcription start site (TSS)) with more A+T rich content was linked to activated promoters [35,36]. PintI1 shares some characteristics of (p)ppGpp activated promoters (conserved bases in the -10 region, T and A bases in the discriminator region and TSS [35,37]).…”

Section: Discussionmentioning

confidence: 99%

Microniches in biofilm depth are hot-spots for antibiotic resistance acquisition in response to in situ stress

Tlili

Ploy

2021

Preprint

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Class 1 integrons play a major role in antibiotic resistance dissemination among Gram-negative bacteria. They are genetic platforms able to capture, exchange and express antibiotic resistance gene cassettes. The integron integrase, whose expression is regulated by the bacterial SOS response, is the key element of the integron catalyzing insertion/excision/shuffling of gene cassettes. We previously demonstrated that the basal level of integrase expression and in consequence, its activity, is increased via the starvation-induced stringent response in the biofilm population. However, biofilms are heterogeneous environments where bacteria are under various physiological states. Here we thus analyzed at the bacterial level, the SOS response and integrase expression within the biofilm, using confocal microscopy and flow cytometry. We showed that in the absence of exogenous stress, only a small number of bacteria (~ 1%) located in the depth of the biofilm induce the SOS-response leading to a high level of integrase expression, through both a stringent response-dependent and -independent manner. Our results thus indicate that few bacteria located in microniches of the biofilm depth undergo sufficient endogenous stress to promote the acquisition of antibiotic resistance, forming a reservoir of bacteria ready to rapidly resist antibiotic treatments.

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“…Cell aggregation assay. Cell aggregation assays were performed described 80 with some modifications. The corresponding cultures were grown in LB medium for 16 h at 25 °C or 37 °C with constant agitation (200 rpm).…”

Section: Methodsmentioning

confidence: 99%

Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli

et al. 2021

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Enteroaggregative Escherichia coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC strains harbor a virulence plasmid (pAA2) that encodes, among other virulence determinants, the aggR gene. The expression of the AggR protein leads to the expression of several virulence determinants in both plasmids and chromosomes. In this work, we describe a novel mechanism that influences AggR expression. Because of the absence of a Rho-independent terminator in the 3′UTR, aggR transcripts extend far beyond the aggR ORF. These transcripts are prone to PNPase-mediated degradation. Structural alterations in the 3′UTR result in increased aggR transcript stability, leading to increased AggR levels. We therefore investigated the effect of increased AggR levels on EAEC virulence. Upon finding the previously described AggR-dependent virulence factors, we detected novel AggR-regulated genes that may play relevant roles in EAEC virulence. Mutants exhibiting high AggR levels because of structural alterations in the aggR 3′UTR show increased mobility and increased pAA2 conjugation frequency. Furthermore, among the genes exhibiting increased fold change values, we could identify those of metabolic pathways that promote increased degradation of arginine, fatty acids and gamma-aminobutyric acid (GABA), respectively. In this paper, we discuss how the AggR-dependent increase in specific metabolic pathways activity may contribute to EAEC virulence.

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ppGpp mediates the growth phase‐dependent regulation of agn43, a phase variable gene, by stimulating its promoter activity

Cited by 5 publications

References 47 publications

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

Possible Roles for Basal Levels of (p)ppGpp: Growth Efficiency Vs. Surviving Stress

Microniches in biofilm depth are hot-spots for antibiotic resistance acquisition in response to in situ stress

Modulation of AggR levels reveals features of virulence regulation in enteroaggregative E. coli

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