(p)ppGpp regulates type 1 fimbriation of <i>Escherichia coli</i> by modulating the expression of the site‐specific recombinase FimB

Åberg, Anna; Shingler, Victoria; Balsalobre, Carlos

doi:10.1111/j.1365-2958.2006.05191.x

Cited by 107 publications

(106 citation statements)

References 59 publications

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“…Moreover, (p)ppGpp synthases are necessary for transcription of vpsR and vpsT, which encode transcriptional regulators of exopolysaccharide synthesis in Vibrio cholerae (He et al, 2012). Additionally, (p)ppGpp-mediated regulation of biofilm formation is associated with expression of type 1 fimbriae in E. coli (Aberg et al, 2006). Taken together, these observations indicate that the stringent response promotes biofilm formation in many bacteria.…”

Section: Discussionmentioning

confidence: 84%

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

et al. 2013

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Bordetella pertussis, the causative agent of whooping cough, is highly adapted to cause human infection. The production of virulence factors, such as adhesins and toxins, is just part of an array of mechanisms by which B. pertussis causes infection. The stringent response is a global bacterial response to nutritional limitation that is mediated by the accumulation of cellular ppGpp and pppGpp [termed together as (p)ppGpp]. Here, we demonstrate that production of (p)ppGpp was controlled by RelA and SpoT proteins in B. pertussis, and that mutation-induced loss of both proteins together caused deficiencies in (p)ppGpp production. The (p)ppGpp-deficient mutants also exhibited defects in growth regulation, decreases in viability under nutritionally limited conditions, increases in susceptibility to oxidative stress and defects in biofilm formation. Analysis of the secreted proteins and the respective transcripts showed that lack of (p)ppGpp led to decreased expression of fim3 and bsp22, which encode a fimbrial subunit and the selfpolymerizing type III secretion system tip protein, respectively. Moreover, electron microscopic analysis also indicated that (p)ppGpp regulated the formation of filamentous structures. Most virulence genes -including fim3 and bsp22 -were expressed in the Bvg + phase during which the BvgAS two-component system was activated. Although fim3 and bsp22 were downregulated in a (p)ppGpp-deficient mutant, normal expression of fhaB, cyaA and ptxA persisted. Lack of coherence between virulence gene expression and (p)ppGpp production indicated that (p)ppGpp did not modulate the Bvg phase. Taken together, our data indicate that (p)ppGpp may govern an as-yet-unrecognized system that influences B. pertussis pathogenicity.

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Section: Discussionmentioning

confidence: 84%

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

et al. 2013

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“…The control of fimbria expression by ppGpp occurs through the promoter activation of the site-specific recombinase FimB, an enzyme that inverts the 314-bp promoter of the fimAICDFGH operon. Following transcriptional activation, FimB flips the fim promoter from its "off" orientation to its productive "on" position, thereby activating the transcription of genes encoding the structural components of type I fimbriae (2). Entry into the stationary phase results in the ppGpp-mediated activation of both the fimB and fimA promoters, increasing the frequency of adherent cells.…”

Section: Uropathogenic Escherichia Colimentioning

confidence: 99%

ppGpp Conjures Bacterial Virulence

Dalebroux

Svensson

Gaynor

et al. 2010

Microbiol Mol Biol Rev

333

364

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SUMMARY Like for all microbes, the goal of every pathogen is to survive and replicate. However, to overcome the formidable defenses of their hosts, pathogens are also endowed with traits commonly associated with virulence, such as surface attachment, cell or tissue invasion, and transmission. Numerous pathogens couple their specific virulence pathways with more general adaptations, like stress resistance, by integrating dedicated regulators with global signaling networks. In particular, many of nature's most dreaded bacteria rely on nucleotide alarmones to cue metabolic disturbances and coordinate survival and virulence programs. Here we discuss how components of the stringent response contribute to the virulence of a wide variety of pathogenic bacteria.

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“…Because inactivation of the dksA gene increases the activities of numerous promoters in vivo in addition to those for rRNA, and ppGpp/DksA directly inhibits some of these promoters in vitro (11,(32)(33)(34), we decided to examine whether control of transcription initiation by ppGpp/DksA might also play a direct role in the regulation of r-protein synthesis. Here we report that many of the major r-protein promoters are specifically inhibited by ppGpp/DksA in vitro, that the activities of the same r-protein promoters increase in strains lacking dksA, and that ppGpp/ DksA-regulated r-protein promoters are not stringently controlled in strains lacking dksA.…”

mentioning

confidence: 99%

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

Lemke

Sanchez-Vazquez²,

Burgos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

140

144

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We show here that the promoters for many of the Escherichia coli ribosomal protein operons are regulated directly by two transcription factors, the small RNA polymerase-binding protein DksA and the nutritional stress-induced nucleotide ppGpp. ppGpp and DksA work together to inhibit transcription initiation from ribosomal protein promoters in vitro and in vivo. The degree of promoter regulation by ppGpp/DksA varies among the r-protein promoters, but some are inhibited almost as much as rRNA promoters. Thus, many r-protein operons are regulated at the level of transcription in addition to their control by the classic translational feedback systems discovered ∼30 y ago. We conclude that direct control of r-protein promoters and rRNA promoters by the same signal, ppGpp/DksA, makes a major contribution to the balanced and coordinated synthesis rates of all of the ribosomal components.ribosome synthesis | transcriptional control | stringent response | translational control P rotein synthesis is the major consumer of cellular energy in bacteria. Because the number of ribosomes is the primary determinant of the level of translation, and ribosome synthesis itself is an energy-intensive process, there are mechanisms that prevent over-or underinvestment of cellular resources in ribosome synthesis (1). Both ribosomal RNA (rRNA) and ribosomal protein (r-protein) synthesis rates are thereby tightly regulated in Escherichia coli (for reviews, see refs. 2, 3).One of the earliest reported examples of regulation of bacterial ribosome synthesis is a stress response referred to as "the stringent response," in which rRNA transcription is inhibited in cells starved for amino acids or some other nutrients (4). In this response, uncharged tRNAs induce the ribosome-associated RelA and/or SpoT proteins to synthesize ppGpp (5-7). [The term "ppGpp" is used here to describe both the unusual nucleotide guanosine-3′,5′-(bis)pyrophosphate and its pentaphosphate precursor.] ppGpp concentrations change not only after complete starvations but also after less severe shifts in nutritional conditions, coordinating rRNA synthesis with the need for protein synthesis. Shifts to a more favorable nutritional condition result in a decrease in the concentration of ppGpp and a corresponding increase in rRNA promoter activity, whereas shifts to a less favorable condition result in an increase in ppGpp and a corresponding decrease in rRNA transcription (8).ppGpp binds directly to E. coli RNA polymerase (RNAP) and inhibits transcription from rRNA promoters (9), although the identity of the ppGpp binding site on RNAP remains unclear (10). However, for ppGpp to exert its full effect on transcription, RNAP has to be modified by the small protein, DksA (11,12). Unlike ppGpp, DksA is present at high concentrations in cells under all conditions that have been examined (11,13). rRNA transcription initiation is also regulated by the concentration of the first nucleotide in the transcript (8,14) and by at least one DNA binding factor, the 11.2-kDa Fis protein (15). Tog...

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(p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site‐specific recombinase FimB

Cited by 107 publications

References 59 publications

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

Role of (p)ppGpp in biofilm formation and expression of filamentous structures in Bordetella pertussis

ppGpp Conjures Bacterial Virulence

Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA

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