Bringing host-cell takeover by pathogenic bacteria to center stage

Dubreuil, Ron; Segev, Nava

doi:10.4161/cl.1.4.18984

Cited by 6 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 and Figs. S2A and S2B ) suggests that the binding is firm, an idea consistent with reports for other effector-Rab interactions (Dubreuil & Segev, 2011; Schoebel et al, 2011). The mechanism by which EspH affects the host Rabs is not clear.…”

Section: Discussionsupporting

confidence: 87%

“…Studies have shown that human bacterial pathogens (e.g., Salmonella enterica , Legionella pneumophila , Shigella flexneri , Listeria monocytogenes ) target Rab GTPases to establish a replication niche that enables their survival within the host cells (Dubreuil & Segev, 2011; Sherwood & Roy, 2013; Stein et al, 2012). Moreover, studies have indicated that type III secreted effectors can target host Rab GTPases directly (Boddy et al, 2021; Gan et al, 2020; Goody et al, 2012; Mousnier et al, 2014; Spano et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Nandi,

Ramachandran,

Shalev

et al. 2024

Preprint

View full text Add to dashboard Cite

EnteropathogenicE. coli(EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulent proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues. Mutating these sites abolished the EspH ability to inhibit the Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Nandi,

Ramachandran,

Shalev

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Notably, mathematical modeling of the evolution of the insect endosymbiont Buchnera aphidicola showed that metabolic requirements could determine not only the end point of genomic reduction but to some extent also the order of the gene deletion 38 . Moreover, the reductive trend is countered by proliferation of genes involved in parasite-host interaction such as, for example, ankyrin repeat proteins that act as secreted virulence factors 39 – 40 . Quantitatively, however, in most parasites and symbionts, these processes make a relatively minor contribution compared to the massive genome reduction.…”

Section: Box 1 Reconstruction Of Ancestral Genomes: Maximum Parsimonymentioning

confidence: 99%

Genome reduction as the dominant mode of evolution

2013

View full text Add to dashboard Cite

A common belief is that evolution generally proceeds towards greater complexity at both the organismal and the genomic level, numerous examples of reductive evolution of parasites and symbionts notwithstanding. However, recent evolutionary reconstructions challenge this notion. Two notable examples are the reconstruction of the complex archaeal ancestor and the intron-rich ancestor of eukaryotes. In both cases, evolution in most of the lineages was apparently dominated by extensive loss of genes and introns, respectively. These and many other cases of reductive evolution are consistent with a general model composed of two distinct evolutionary phases: the short, explosive, innovation phase that leads to an abrupt increase in genome complexity, followed by a much longer reductive phase, which encompasses either a neutral ratchet of genetic material loss or adaptive genome streamlining. Quantitatively, the evolution of genomes appears to be dominated by reduction and simplification, punctuated by episodes of complexification.

show abstract

“…Bacteria use the proteins containing typically eukaryotic domains encoded by horizontally acquired DNA sequences as injected “effector” molecules to modulate host cell metabolism and defenses in order to facilitate the infection process [ 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 ]. The ability of many infectious bacteria to grow in diverse eukaryotic hosts, such as amoebae and mammals [ 230 ], apparently plays an important role in the acquisition of eukaryotic domains from one kind of host (e.g., amoebae) and their utilization as invasion functions in another kind of host (e.g., mammals).…”

Section: Adaptations Acquired and Comingled By Horizontal Transfermentioning

confidence: 99%

Nothing in Evolution Makes Sense Except in the Light of Genomics: Read–Write Genome Evolution as an Active Biological Process

Shapiro

2016

Biology

View full text Add to dashboard Cite

The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess “Read–Write Genomes” they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.

show abstract

Bringing host-cell takeover by pathogenic bacteria to center stage

Cited by 6 publications

References 21 publications

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Genome reduction as the dominant mode of evolution

Nothing in Evolution Makes Sense Except in the Light of Genomics: Read–Write Genome Evolution as an Active Biological Process

Contact Info

Product

Resources

About