Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function

Fischer, Wolfgang; Tegtmeyer, Nicole; Stingl, Kerstin; Backert, Steffen

doi:10.3389/fmicb.2020.01592

Cited by 47 publications

(46 citation statements)

References 123 publications

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“… 46 T4SSs was involved in Helicobacter pylori adaptation to the hostile environment in the human stomach. 47 Further research is needed to clarify functions and mechanisms of secretion system in A. baumannii during within-host evolution.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Li¹,

Zhang²,

Wang³

et al. 2021

IDR

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Introduction Colonization of the respiratory tract by Acinetobacter baumannii has been established as an independent risk factor for bacteremia. However, within-host evolution of A. baumannii in bacteremia has not been extensively investigated. Methods We performed whole-genome sequencing to discover the evolutionary characteristics that accompany the transition from respiratory tract carriage to bloodstream infection in three patients with A. baumannii bacteremia. Results Within-host genetic diversity was identified. A total of 21 single nucleotide variants (SNVs) were detected. Genic and intergenic evolution occurred particularly in secretion system, DNA recombination, and cell motility genes. Intergenic SNVs occurred more frequently compared to synonymous and non-synonymous SNVs, which indicated potential transcription or translation regulation. Non-synonymous mutations mostly occurred during the transition from respiratory tract carriage to bloodstream infection. Isolates of clonal complex 208 (CC208) had lower substitution rate with approximately 10 −6 nucleotide substitutions per site year −1 , compared with non-CC208 isolates (approximately 10 −5 ). We found evidence for the occurrence of recombination in one patient. A total of 259 genes were found to be gained or lost during the within-host evolution, and 231 genes were only detected in one patient. Gene function annotation results suggested that most genes (71/259) were related to replication, recombination, and repair. Universal bloodstream specific genes were not found in all three patients, and only one putative membrane protein related gene was lost in two patients. Conclusion Our results indicated that within-host evolution of A. baumannii bacteremia was driven by mutations, gene content changes, and limited effect of recombination. Gene content diversity between different patients was identified, which suggested interplay of both host and pathogen factors in within-host genetic diversity. Secretion system-related genes showed higher frequency of genomic variations during the within-host evolution. Our findings enhanced our understanding of within-host evolution of A. baumannii bacteremia and provided a framework for discovering novel genomic changes and pathogenicity genes important for bacteremia, which will be validated in future studies.

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Section: Discussionmentioning

confidence: 99%

Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Li¹,

Zhang²,

Wang³

et al. 2021

IDR

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“…The Cag type IV secretion systems (T4SSs) in Helicobacter pylori facilitates the delivery of the CagA effector protein and pro-in ammatory signal transduction through translocated ADP-heptose and chromosomal DNA, while various structural pilus proteins can target host cell receptors such as integrins or toll-like receptor-5. T4SSs was involved in H. pylori adaptation to the hostile environment in the human stomach [18]. Further research is needed to clarify the function and mechanisms of secretion system in A. baumannii during within host evolution.…”

Section: Discussionmentioning

confidence: 99%

Within-host Evolution of Acinetobacter Baumannii in Clinical Bacteremia Patients

Li¹,

Zhang²,

Wang³

et al. 2020

Preprint

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Background: Acinetobacter baumannii colonizing the respiratory tract has been established as an independent risk factor for bacteremia. However, within-host evolution of A. baumannii in bacteremia has not been extensively investigated. Here we performed whole genome sequencing to discover the evolutionary characteristics that accompany the transition from respiratory tract carriage to bloodstream infection in three A. baumannii bacteremia patients.Results: Within-host genetic diversity was identified. A total of twenty-one SNVs were detected. Genic and intergenic evolution occurred particularly in secretion system, DNA recombination and cell motility genes. Intergenic SNVs occurred more frequently than synonymous and non-synonymous SNVs, which indicated potential transcription or translation regulation. Non-synonymous mutations mostly occurred during the transition from the respiratory tract carriage to the bloodstream infection. Isolates of clonal complex 208 (CC208) had lower substitution rate with approximately 10-6 nucleotide substitutions per site year-1, compared with non CC208 isolates (approximately 10-5). We found evidence for the occurrence of recombination in one patient. Gene content showed patient specificity, and isolates within a single host had constrained gene content diversity.Conclusions: Our results indicated that high within-host diversity was driven by rapid mutation rates and limited effect of recombination in A. baumannii from respiratory tract carriage to bacteremia.

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“…The H. pylori Cag T4SS is of interest because of the frequency with which it contributes to human illness (Cover et al., 2020; Fischer et al., 2020). About half of all humans worldwide are persistently colonized with H. pylori .…”

Section: Figurementioning

confidence: 99%

Tracking bacterial effector protein delivery into host cells

Cover

2021

Molecular Microbiology

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Bacterial Type IV secretion systems (T4SSs) are a functionally heterogeneous group of nanomachines that can deliver substrates into a wide range of target cells. The Helicobacter pylori Cag T4SS has an important role in the pathogenesis of gastric cancer. CagA, the only effector protein known to be secreted by the H. pylori Cag T4SS, enters human gastric cells and causes alterations in intracellular signaling that are linked to cancer pathogenesis. Understanding the molecular mechanisms by which CagA is delivered into gastric cells has been hindered by the lack of robust methods for monitoring this process. A publication in this issue of Molecular Microbiology describes a split luciferase assay for monitoring T4SS‐mediated translocation of CagA into host cells. The use of this translocation reporter allowed the quantification of CagA translocation in real‐time assays, thereby facilitating the analysis of the kinetics of CagA delivery. This system also allowed the tracking of several types of CagA fusion proteins and confirmed that protein unfolding is important for secretion by the Cag T4SS. This commentary discusses T4SS‐dependent delivery of H. pylori CagA into host cells and the use of the split luciferase system for monitoring bacterial protein secretion and delivery into target cells.

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Four Chromosomal Type IV Secretion Systems in Helicobacter pylori: Composition, Structure and Function

Cited by 47 publications

References 123 publications

Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Evolution of Acinetobacter baumannii in Clinical Bacteremia Patients

Within-host Evolution of Acinetobacter Baumannii in Clinical Bacteremia Patients

Tracking bacterial effector protein delivery into host cells

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