Characterization of TelE, a T7SS LXG Effector Exhibiting a Conserved C-Terminal Glycine Zipper Motif Required for Toxicity

Teh, Wooi Keong; Ding, Yichen; Gubellini, Francesca; Filloux, Alain; Poyart, Claire; Givskov, Michael; Dramsi, Shaynoor

doi:10.1128/spectrum.01481-23

Cited by 6 publications

(6 citation statements)

References 83 publications

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“…We next wanted to test if the protein product of each gene required for TelA secretion is exported from cells. We and others previously found that the targeting factors for TelC toxins, LapC1 and LapC2, are not secreted from cells (12,15). To test if this is also the case for LapA3 and LapA4, we expressed C-terminal VSV-G tagged versions of these proteins and performed western blot analyses on cell and culture supernatant fractions of wild-type and T7SS-null (DessC) strains of Si B196 .…”

Section: Identification Of Two New Families Of Lxg Toxin Targeting Fa...mentioning

confidence: 98%

Structure of a tripartite protein complex that targets toxins to the type VII secretion system

Klein,

Shah,

Gkragkopoulou

et al. 2023

Preprint

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Type VII secretion systems are membrane-embedded nanomachines used by Gram-positive bacteria to export effector proteins from the cytoplasm to the extracellular environment. Many of these effectors are polymorphic toxins comprised of an N-terminal Leu-x-Gly (LXG) domain of unknown function and a C-terminal toxin domain that inhibits the growth of bacterial competitors. In recent work, it was shown that LXG effectors require two cognate Lap proteins for T7SS-dependent export. Here, we present the 2.6 Angstrom structure of the LXG domain of the TelA toxin from the opportunistic pathogen Streptococcus intermedius in complex with both of its cognate Lap targeting factors. The structure reveals an elongated alpha-helical bundle within which each Lap protein makes extensive hydrophobic contacts with either end of the LXG domain. Remarkably, despite low overall sequence identity, we identify striking structural similarity between our LXG complex and PE-PPE heterodimers exported by the distantly related ESX type VII secretion systems of Mycobacteria implying a conserved mechanism of effector export among diverse Gram-positive bacteria. Overall, our findings demonstrate that LXG domains, in conjunction with their cognate Lap targeting factors, represent a tripartite secretion signal for a widespread family of T7SS toxins.

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Section: Identification Of Two New Families Of Lxg Toxin Targeting Fa...mentioning

confidence: 98%

Structure of a tripartite protein complex that targets toxins to the type VII secretion system

Klein,

Shah,

Gkragkopoulou

et al. 2023

Preprint

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“…that encodes a putative type VII secretion system contributing to gut colonization and the development of colon tumors [ 19 ]. Teh et al in 2023 further characterized one of the type VII secretion system effector proteins, named herein TelE, exhibiting their toxic activity of promoting the loss of membrane integrity [ 20 ]. Pasquereau-Kotula et al demonstrate the oncogenic role of Sgg.…”

Section: Discussionmentioning

confidence: 99%

Sciatica caused by spinal epidural abscess as the initial clinical presentation of colon cancer: a rare case report and review of literature

Lu,

Tung,

Chiang

et al. 2024

BMC Infect Dis

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Background Colorectal cancer is one of the most frequently diagnosed forms of cancer, and it is associated with several common symptoms and signs such as rectal bleeding, altered bowel habits, abdominal pain, anemia, and unintentional weight loss. Sciatica, a debilitating condition in which the patient experiences paresthesia and pain in the dermatome of associated lumbosacral nerve roots or sciatic nerve distribution, is not considered one of these. Here we present a case of colorectal cancer manifesting symptoms of sciatica alone. Case presentation A 68-year-old male presented with progressive lower back pain radiating to his left thigh and calf over L5/S1 dermatome. Sciatica was suspected and initially underwent conservative treatment with analgesics. However, the symptoms progressed and MRI revealed an epidural abscess surprisingly. Surgical debridement was performed and pus culture isolated Streptococcus gallolyticus. Based on the strong association of S. gallolyticus with colorectal cancer, the presence of this pathogen prompted further tumor evaluation, even in the absence of the typical symptoms and signs. This investigation ultimately leads to the diagnosis of sigmoid adenocarcinoma. Conclusions Although rare, sciatica caused by S. gallolyticus infection of the spinal epidural space may serve as the initial presentation of colorectal cancer. Physicians should be aware of the strong association between S. gallolyticus and colorectal cancer. Based on what we currently know about the condition; a thorough systematic assessment of occult neoplasia for patients with S. gallolyticus infection is recommended.

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“…A further TelE LXG toxin has also been described in Streptococcus gallolyticus [ 17 ]. TelE carries a bacteriocin-like glycine zipper motif, which inserts into and destabilises target membranes, and is homologous to S. aureus EsxX.…”

Section: The T7ssb As a Bacterial Weaponmentioning

confidence: 99%

“… S. aureus EsxC, EsxB and EsxD have previously been shown to be secreted substrates, suggesting they are co-secreted with EsaD. Similarly, two small WXG100-like proteins encoded directly upstream of the S. gallolyticus LXG toxin TelE are T7-secreted [ 17 ]. The streptococcal Lap proteins are secreted with their cognate LXG domain protein in some cases but not all [ 72, 82 ], although it remains a possibility that these proteins are degraded following secretion and so not detected in the secretome.…”

Section: Strain-specific Secretion Factors and T7ss Targeting Signalsmentioning

confidence: 99%

“…Beyond the presence of WXG100- and FtsK/SpoIII-family proteins, the components of the T7SS in Actinomycetota are unrelated to those found in Bacillota, and the two systems have therefore been designated T7SSa and T7SSb, respectively. The T7SSb is widely distributed among pathogenic and non-pathogenic species of the Bacillota phylum, having been studied in species of Staphylococcus, Streptococcus, Bacillus, Enterococcus and Listeria [12–20].…”

Section: Introductionmentioning

confidence: 99%

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Interbacterial competition mediated by the type VIIb secretion system

Boardman,

Palmer,

Alcock

2023

Microbiology

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Successful occupancy of a given niche requires the colonising bacteria to interact extensively with the biotic and abiotic environment, including other resident microbes. Bacteria have evolved a range of protein secretion machines for this purpose with eleven such systems identified to date. The type VIIb secretion system (T7SSb) is utilised by Bacillota to secrete a range of protein substrates, including antibacterial toxins targeting closely related strains, and the system as a whole has been implicated in a range of activities such as iron acquisition, intercellular signalling, host colonisation and virulence. This review covers the components and secretion mechanism of the T7SSb, the substrates of these systems and their roles in Gram-positive bacteria, with a focus on interbacterial competition.

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Characterization of TelE, a T7SS LXG Effector Exhibiting a Conserved C-Terminal Glycine Zipper Motif Required for Toxicity

Cited by 6 publications

References 83 publications

Structure of a tripartite protein complex that targets toxins to the type VII secretion system

Structure of a tripartite protein complex that targets toxins to the type VII secretion system

Sciatica caused by spinal epidural abscess as the initial clinical presentation of colon cancer: a rare case report and review of literature

Interbacterial competition mediated by the type VIIb secretion system

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