Recent insights into type-3 secretion system injectisome structure and mechanism of human enteric pathogens

Chen, Poyin; Goldberg, Marcia B.

doi:10.1016/j.mib.2022.102232

Cited by 5 publications

(2 citation statements)

References 66 publications

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“…This is supported by the observation that the p2939_90_1 locus was not present in all sequenced P. alcalifaciens genomes, and its distribution is not monophyletic (see Figure 1), potentially indicating horizontal movement of this locus. Both the chromosomal and plasmid p2939_90_1 loci contain all the required components to form a type III secretion apparatus (Chen and Goldberg, 2023), with the p2939_90_1 locus containing some additional, non-essential genes for the formation of a type III secretion apparatus. Moreover, we predict that as many as 26 effector proteins are encoded by p2939_90_1 which are likely to require the apparatus encoded on the p2939_90_1 for secretion, independent of the omnipresent chromosomally encoded type III secretion apparatus.…”

Section: Discussionmentioning

confidence: 99%

EnteropathogenicProvidencia alcalifaciens: A subgroup ofP. alcalifaciensthat causes diarrhea

Bulach,

Carter,

Albert

2024

Preprint

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Even though Providencia alcalifaciens is considered as a normal flora of the large intestine, there are reports of it causing diarrhea. In a previous study, a strain, 2939/90 obtained as a pure stool culture from a dead diarrheal patient was shown to cause invasion and actin condensation in mammalian cells, and diarrhea in a rabbit model. In a subsequent study, four TnphoA mutants of 2939/90 produced negligible invasion and actin condensation in mammalian cells. In the present study, the parent strain was sequenced by short-read and long-read sequencing, and the mutants by short read sequencing. In all four mutants, a TnphoA insertion was detected in the type three secretion system (T3SS) locus present on the largest of four plasmids (p2939_90_1) and not in a seemingly independent, functional T3SS locus on the chromosome. A survey of 52 genomes of P. alcalifaciens available in the public database identified the chromosomal T3SS locus in all strains, including both P. alcalifaciens genomic clades that we have classified as (group A) and (group B); a highly related gene layout and gene synteny flanking the locus suggested that these chromosomal loci are orthologous. There is a low sequence similarity between the chromosomal and plasmid-borne T3SS; a survey of plasmid T3SS showed its presence in only 21 of 52 genomes and mostly in group A genomes. Group A included several isolates from an outbreak of haemorrhagic diarrhea in dogs. Using prediction software (EffectiveDB), we detected several known and unknown effectors flanking the plasmid T3SS locus. The observation that TnphoA insertion only in the plasmid T3SS locus affected the invasion phenotype suggested that this locus is critical for causation of diarrhea. This leads us to conclude that a subgroup of P. alcalifaciens that possesses this plasmid-borne T3SS locus (in the case of strain, 2939/90) can cause diarrheal disease. We name this subgroup as enteropathogenic P. alcalifaciens (EPA). EPA should be included in future studies of etiology of diarrhea. A unique sequence that may be present in the T3SS locus in the plasmid may be investigated as a marker in a simple molecular test for diagnosis of EPA.

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Section: Discussionmentioning

confidence: 99%

EnteropathogenicProvidencia alcalifaciens: A subgroup ofP. alcalifaciensthat causes diarrhea

Bulach,

Carter,

Albert

2024

Preprint

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“…As many other Gram negative pathogens and symbionts, Salmonella relies on type III secretion systems (T3SS) for its interactions with mammalian host cells ( 2 ). These systems, also known as injectisomes, are complex molecular devices ( 3 ) that allow some bacteria to inject specific proteins, known as effectors ( 4 ), directly into host cells. S. enterica possesses two distinct T3SS, T3SS1 and T3SS2, which are encoded by Salmonella pathogenicity island 1 (SPI1) and Salmonella pathogenicity island 2 (SPI2), respectively.…”

Section: Introductionmentioning

confidence: 99%

Specificities and redundancies in the NEL family of bacterial E3 ubiquitin ligases of Salmonella enterica serovar Typhimurium

Bullones-Bolaños,

Martín-Muñoz,

Vallejo-Grijalba

et al. 2024

Front. Immunol.

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Salmonella enterica serovar Typhimurium expresses two type III secretion systems, T3SS1 and T3SS2, which are encoded in Salmonella pathogenicity island 1 (SPI1) and SPI2, respectively. These are essential virulent factors that secrete more than 40 effectors that are translocated into host animal cells. This study focuses on three of these effectors, SlrP, SspH1, and SspH2, which are members of the NEL family of E3 ubiquitin ligases. We compared their expression, regulation, and translocation patterns, their role in cell invasion and intracellular proliferation, their ability to interact and ubiquitinate specific host partners, and their effect on cytokine secretion. We found that transcription of the three genes encoding these effectors depends on the virulence regulator PhoP. Although the three effectors have the potential to be secreted through T3SS1 and T3SS2, the secretion of SspH1 and SspH2 is largely restricted to T3SS2 due to their expression pattern. We detected a role for these effectors in proliferation inside fibroblasts that is masked by redundancy. The generation of chimeric proteins allowed us to demonstrate that the N-terminal part of these proteins, containing the leucine-rich repeat motifs, confers specificity towards ubiquitination targets. Furthermore, the polyubiquitination patterns generated were different for each effector, with Lys48 linkages being predominant for SspH1 and SspH2. Finally, our experiments support an anti-inflammatory role for SspH1 and SspH2.

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Oxamic acid thiohydrazides and hydrazones based on them as convenient starting compounds for the synthesis of S- and N-containing heterocyclic products. A mini-review

Krayushkin,

Yarovenko

2024

Arabian Journal of Chemistry

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Recent insights into type-3 secretion system injectisome structure and mechanism of human enteric pathogens

Cited by 5 publications

References 66 publications

EnteropathogenicProvidencia alcalifaciens: A subgroup ofP. alcalifaciensthat causes diarrhea

EnteropathogenicProvidencia alcalifaciens: A subgroup ofP. alcalifaciensthat causes diarrhea

Specificities and redundancies in the NEL family of bacterial E3 ubiquitin ligases of Salmonella enterica serovar Typhimurium

Oxamic acid thiohydrazides and hydrazones based on them as convenient starting compounds for the synthesis of S- and N-containing heterocyclic products. A mini-review

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