The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting<i>Chlamydia</i>effectors from degradation

Bastidas, Robert J.; Kędzior, Mateusz; Dolat, Lee; Sixt, Barbara S.; Pruneda, Jonathan N.; Valdivia, Raphael H.

doi:10.1101/2023.02.28.530337

Cited by 4 publications

(2 citation statements)

References 95 publications

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“…The DUB function of ChlaDUB1 has been linked to several biological processes, including inhibition of NF‐κB signaling, Mcl‐1 stabilization, and Golgi fragmentation/recruitment to the Chlamydia ‐containing inclusion (Le Negrate et al , 2008; Fischer et al , 2017; Pruneda et al , 2018; Auer et al , 2020). Recently, a role for ChlaDUB1 acetyltransferase function has been described in protecting other Chlamydia effectors from Ub‐mediated degradation, thereby supporting bacterial egress (preprint: Bastidas et al , 2023). Whether ChlaDUB1 is unique in its ability to catalyze both proteolysis and acetylation remains to be seen.…”

Section: Ub‐like Hydrolysis By Ce‐clan Proteasesmentioning

confidence: 99%

Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

2023

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Regulation through post‐translational ubiquitin signaling underlies a large portion of eukaryotic biology. This has not gone unnoticed by invading pathogens, many of which have evolved mechanisms to manipulate or subvert the host ubiquitin system. Bacteria are particularly adept at this and rely heavily upon ubiquitin‐targeted virulence factors for invasion and replication. Despite lacking a conventional ubiquitin system of their own, many bacterial ubiquitin regulators loosely follow the structural and mechanistic rules established by eukaryotic ubiquitin machinery. Others completely break these rules and have evolved novel structural folds, exhibit distinct mechanisms of regulation, or catalyze foreign ubiquitin modifications. Studying these interactions can not only reveal important aspects of bacterial pathogenesis but also shed light on unexplored areas of ubiquitin signaling and regulation. In this review, we discuss the methods by which bacteria manipulate host ubiquitin and highlight aspects that follow or break the rules of ubiquitination.

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Section: Ub‐like Hydrolysis By Ce‐clan Proteasesmentioning

confidence: 99%

Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

2023

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“…L. pneumophila effectors LegC2, LegC3, and LegC7 directly cooperate-forming a SNARE-like complex with the human hVAMP4 protein to modulate membrane fusion (Shi et al, 2016). Another emerging class of effectors, metaeffectors ("effectors of effectors"), do not target host proteins but instead, once inside the host, directly bind and regulate the activity of other effectors (Kubori et al, 2010;Magori & Citovsky, 2011;Urbanus et al, 2016;Joseph & Shames, 2021;Bastidas et al, 2024).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive two-hybrid analysis to explore theL. pneumophilaeffector-effector interactome

O’Connor Mount,

Urbanus,

Sheykhkarimli

et al. 2024

Preprint

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Legionella pneumophila uses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identified L. pneumophila effectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. L. pneumophila has the largest contingent of a new class of effectors, so called "metaeffectors" that directly regulate the activity of other effectors in the host. A defining quality of metaeffectors is the direct, physical interaction of the metaeffector with its cognate target effector. Metaeffectors identification to date has depended on phenotypes in heterologous systems, experimental serendipity and they represent only one class of physical interactions between effectors. Using a multiplexed, sequence-based yeast two-hybrid technology we screened the entire L. pneumophila effector proteome and components of the Dot/Icm type IV secretion system for protein-protein interactions (>167,000 protein combinations). Our screen captured 52 protein interactions, including 8 known and 44 novel protein interactions. Most notably, we identified ten novel effector-effector interactions, doubling the number of known effector-effector interactions.

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Identification of homologs of the Chlamydia trachomatis effector CteG reveals a family of Chlamydiaceae type III secreted proteins that can be delivered into host cells

Pereira,

da Cunha,

Leal

et al. 2024

Med Microbiol Immunol

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Chlamydiae are a large group of obligate endosymbionts of eukaryotes that includes the Chlamydiaceae family, comprising several animal pathogens. Among Chlamydiaceae, Chlamydia trachomatis causes widespread ocular and urogenital infections in humans. Like many bacterial pathogens, all Chlamydiae manipulate host cells by injecting them with type III secretion effector proteins. We previously characterized the C. trachomatis effector CteG, which localizes at the host cell Golgi and plasma membrane during distinct phases of the chlamydial infectious cycle. Here, we show that CteG is a Chlamydiaceae-specific effector with over 60 homologs phylogenetically categorized into two distinct clades (CteG I and CteG II) and exhibiting several inparalogs and outparalogs. Notably, cteG I homologs are syntenic to C. trachomatis cteG, whereas cteG II homologs are syntenic among themselves but not with C. trachomatis cteG. This indicates a complex evolution of cteG homologs, which is unique among C. trachomatis effectors, marked by numerous events of gene duplication and loss. Despite relatively modest sequence conservation, nearly all tested CteG I and CteG II proteins were identified as type III secretion substrates using Yersinia as a heterologous bacterial host. Moreover, most of the type III secreted CteG I and CteG II homologs were delivered by C. trachomatis into host cells, where they localized at the Golgi region and cell periphery. Overall, this provided insights into the evolution of bacterial effectors and revealed a Chlamydiaceae family of type III secreted proteins that underwent substantial divergence during evolution while conserving the capacity to localize at specific host cell compartments.

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The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protectingChlamydiaeffectors from degradation

Cited by 4 publications

References 95 publications

Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

Ubiquitin‐targeted bacterial effectors: rule breakers of the ubiquitin system

A comprehensive two-hybrid analysis to explore theL. pneumophilaeffector-effector interactome

Identification of homologs of the Chlamydia trachomatis effector CteG reveals a family of Chlamydiaceae type III secreted proteins that can be delivered into host cells

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