The type III secretion system effector network hypothesis

Sanchez‐Garrido, Julia; Ruano-Gallego, David; Choudhary, Jyoti; Frankel, Gad

doi:10.1016/j.tim.2021.10.007

Cited by 46 publications

(20 citation statements)

References 90 publications

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“…Numerous Gram-negative bacteria are reported to infect host cells that are dependent on the type III secretion system ( Ruano-Gallego et al, 2021 ; Sanchez-Garrido et al, 2021 ). This system is associated with bacterial invasion and intracellular growth, thereby affecting the efficiency of bacterial clearance and initial transient localization ( Kang et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Comparison of Anticancer Activities and Biosafety Between Salmonella enterica Serovar Typhimurium ΔppGpp and VNP20009 in a Murine Cancer Model

Liu

Guo²,

Sun³

et al. 2022

Front. Microbiol.

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Salmonella Typhimurium defective in guanosine 5′-diphosphate-3′-diphosphate (ppGpp) synthesis (ΔppGpp) is an attenuated strain with good biosafety and excellent anticancer efficacy. It has been widely applied in preclinical studies of anticancer therapy for various types of solid cancer. VNP20009 is another genetically modified auxotrophic strain with 108-kb deletion, purI−, msbB−, and many single nucleotide polymorphisms (SNPs); it has shown promising therapeutic efficacy in various preclinical tumor models and entered phase I clinical trials. Here, the invasion activities and virulence of ΔppGpp were obviously lower than those of the VNP20009 strain when tested with cancer cells in vitro. In addition, the MC38 tumor-bearing mice showed comparable cancer suppression when treated with ΔppGpp or VNP20009 intravenously. However, the ΔppGpp-treated mice showed 16.7% of complete cancer eradication and prolonged survival in mice, whereas VNP20009 showed higher toxicity to animals, even with equal tumor size individually. Moreover, we found decreased levels of inflammatory cytokines in circulation but strengthened immune boost in tumor microenvironments of ΔppGpp-treated mice. Therefore, the engineered ΔppGpp has high potential for cancer therapeutics, and it is a promising option for future clinical cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Comparison of Anticancer Activities and Biosafety Between Salmonella enterica Serovar Typhimurium ΔppGpp and VNP20009 in a Murine Cancer Model

Liu

Guo²,

Sun³

et al. 2022

Front. Microbiol.

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“…By native delivery of a tagged T3E upon infection, for example, the EH-PPI network exploited by the T3E could be investigated at different timepoints and/or in different hosts. As effectors seem to function in tightly connected networks, information on their potential cooperativity in the plant cell could also improve our understanding of bacterial pathogen-mediated disease development in plants ( Sanchez-Garrido et al, 2021 ). Finally, collaborative efforts of the scientific community will allow the full functional description of the effectome and help understand the disease in general.…”

Section: Discussionmentioning

confidence: 99%

“…As single T3E mutants rarely show an altered phenotype, T3Es have been hypothesized to form a robust interconnected network, in which the effectors can be seen as nodes and the interaction between the effectors or their cellular partners as edges, providing the bacterium with a certain flexibility ( Sanchez-Garrido et al, 2021 ). However, this network robustness is limited, because individual effectors can become essential when part of the network is perturbed ( Ruano-Gallego et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

From prediction to function: Current practices and challenges towards the functional characterization of type III effectors

2023

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The type III secretion system (T3SS) is a well-studied pathogenicity determinant of many bacteria through which effectors (T3Es) are translocated into the host cell, where they exercise a wide range of functions to deceive the host cell’s immunity and to establish a niche. Here we look at the different approaches that are used to functionally characterize a T3E. Such approaches include host localization studies, virulence screenings, biochemical activity assays, and large-scale omics, such as transcriptomics, interactomics, and metabolomics, among others. By means of the phytopathogenic Ralstonia solanacearum species complex (RSSC) as a case study, the current advances of these methods will be explored, alongside the progress made in understanding effector biology. Data obtained by such complementary methods provide crucial information to comprehend the entire function of the effectome and will eventually lead to a better understanding of the phytopathogen, opening opportunities to tackle it.

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“…In this review, we discussed previously reported besides more recently developed state-of-the-art methods for elucidating (real-time) bacterial effector secretion, and elaborated on their latest advances and shortcomings. Implementation of these methods will enlighten an effector's mode of action by providing knowledge of timing of effector secretion, quantities of secreted effector, order of effector secretion and context-dependent effector network dynamics [110,111]. Integrating these data with for example effector-host protein interaction data or effector expression data (e.g., dual RNA-seq data) will eventually enable us to shed better lights on bacterial effector biology, potentially leading to the development of new therapeutics [112].…”

Section: Discussionmentioning

confidence: 99%

Recent Advancements in Tracking Bacterial Effector Protein Translocation

2022

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Bacteria-host interactions are characterized by the delivery of bacterial virulence factors, i.e., effectors, into host cells where they counteract host immunity and exploit host responses allowing bacterial survival and spreading. These effectors are translocated into host cells by means of dedicated secretion systems such as the type 3 secretion system (T3SS). A comprehensive understanding of effector translocation in a spatio-temporal manner is of critical importance to gain insights into an effector’s mode of action. Various approaches have been developed to understand timing and order of effector translocation, quantities of translocated effectors and their subcellular localization upon translocation into host cells. Recently, the existing toolset has been expanded by newly developed state-of-the art methods to monitor bacterial effector translocation and dynamics. In this review, we elaborate on reported methods and discuss recent advances and shortcomings in this area of tracking bacterial effector translocation.

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The type III secretion system effector network hypothesis

Cited by 46 publications

References 90 publications

Comparison of Anticancer Activities and Biosafety Between Salmonella enterica Serovar Typhimurium ΔppGpp and VNP20009 in a Murine Cancer Model

Comparison of Anticancer Activities and Biosafety Between Salmonella enterica Serovar Typhimurium ΔppGpp and VNP20009 in a Murine Cancer Model

From prediction to function: Current practices and challenges towards the functional characterization of type III effectors

Recent Advancements in Tracking Bacterial Effector Protein Translocation

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