Host cell attachment elicits posttranscriptional regulation in infecting enteropathogenic bacteria

Katsowich, Naama; Elbaz, Netanel; Pal, Ritesh Ranjan; Mills, Erez; Kobi, Simi; Kahan, Tamar; Rosenshine, Ilan

doi:10.1126/science.aah4886

Cited by 65 publications

(103 citation statements)

References 50 publications

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“…Structural studies confirmed dual-site binding (50). This general mechanism of translational repression has been substantiated for numerous E. coli mRNA targets, including csrA itself (5, 9, 11, 14, 20, 22, 23, 52–55). Similar translation repression mechanisms have also been identified in several other bacterial species (31, 56–59).…”

Section: Direct Csra-mediated Regulationmentioning

confidence: 85%

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Global Regulation by CsrA and Its RNA Antagonists

Romeo

Babitzke²

2018

Microbiol Spectr

147

145

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The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In Gammaproteobacteria, small regulatory RNAs that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of E. coli is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to basepairing sRNAs and novel mRNA segments, such as the 3′ UTR and deep within coding regions, predict its participation in yet to be discovered regulatory mechanisms.

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Section: Direct Csra-mediated Regulationmentioning

confidence: 85%

“…Similar translation repression mechanisms have also been identified in several other bacterial species (31, 56–59). In some cases, CsrA binding sites overlap the start codon (11, 22, 23, 55, 58, 59), or initially translated region (5, 15). …”

Section: Direct Csra-mediated Regulationmentioning

confidence: 99%

Global Regulation by CsrA and Its RNA Antagonists

Romeo

Babitzke²

2018

Microbiol Spectr

147

145

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“…The prophage encoded effector NleA is a critical virulence determinant of A/E pathogens (47, 48)(Fig 6). EPEC NleA expression is regulated by a post-transcriptional process where nleA mRNA is bound by the RNA binding protein CsrA to prevent its translation until T3SS-mediated host cell contact (49). CesT was further shown to relieve translation inhibition by interacting and displacing CsrA from the nleA mRNA transcript.…”

Section: Discussionmentioning

confidence: 99%

Tandem tyrosine residues in the EPEC multicargo chaperone CesT support differential type III effector translocation and early host colonization

Runte

Jain

Getz

et al. 2018

Preprint

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Enteropathogenic Escherichia coli (EPEC) are worldwide human enteric pathogens inflicting significant morbidity and causing large economic losses. A type 3 secretion system (T3SS) is critical for EPEC intestinal colonization, and injection of effectors into host cells contributes to cellular subversion and innate immune evasion. Here, we demonstrate that two strictly conserved C-terminal tyrosine residues, Y152 and Y153, within the multicargo T3SS chaperone CesT serve differential roles in regulating effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine attenuated EPEC type 3 effector injection into host cells, and significantly limited Tir effector mediated intimate adherence, a key feature of attaching and effacing pathogenesis. Whereas CesT Y153 supported normal levels of Tir translocation, CesT Y152 was strictly required for the effector NleA to be expressed and subsequently translocated into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y152, Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating Y152 in CesT functionality. A mouse infection model of EPEC intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for strictly conserved tandem tyrosine residues within CesT. Tyrosine 152 of CesT is implicated in NleA expression, providing functional relevance for localized amino acid conservation. Therefore, CesT via its novel C-terminal domain, has relevant roles beyond typical T3SC that interact and stabilize effector proteins.

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“…Induction of the LEE1 promoter via mechanical stress occurs independently of the mode of attachment, such as electrostatic interactions, Tir‐intimin binding, or immobilisation by antibodies (Alsharif et al, ). EPEC shows similar regulation, using the T3SS to sense the host cell and alter gene expression post‐transcriptionally to adapt to its new niche on the epithelium (Katsowich et al, ). Furthermore, the EPEC T3SS gatekeeper proteins SepL and SepD selectively mediate the secretion of translocators and effectors in response to environmental factors, including host cell attachment.…”

Section: Navigating the Gut For Colonisation And Survivalmentioning

confidence: 99%

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

Woodward

Krekhno

2019

Cellular Microbiology

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Gastrointestinal (GI) pathogens enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC), and related mouse pathogen Citrobacter rodentium, are referred to as attaching and effacing (AE) pathogens for the lesions they form upon colonisation of the host epithelium. EPEC, EHEC, and C. rodentium are well known to use a type III secretion system to intimately attach to intestinal cells and secrete bacterial effectors to manipulate host cell processes. Less well known is the ability of AE pathogens to overcome significant physiological and microbial barriers and target specific gut niches for initial colonisation of the host epithelium. This review considers recent work highlighting the biogeography of the GI tract as it applies to colonisation by enteric pathogens, including environmental barriers to enteric infection, signals sensed by AE pathogens for navigation of the GI tract, and the tools AE pathogens use to respond to the changing host environment.

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Host cell attachment elicits posttranscriptional regulation in infecting enteropathogenic bacteria

Cited by 65 publications

References 50 publications

Global Regulation by CsrA and Its RNA Antagonists

Global Regulation by CsrA and Its RNA Antagonists

Tandem tyrosine residues in the EPEC multicargo chaperone CesT support differential type III effector translocation and early host colonization

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

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