Evolutionary aspects of toxin-producing bacteria

Wilson, Brenda A.; Ho, Mengfei

doi:10.1016/b978-0-12-800188-2.00001-x

Cited by 6 publications

(4 citation statements)

References 375 publications

(414 reference statements)

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“…It has been suggested that, by modulating bacterial and host metabolism, CT facilitates fecal–oral transmission of V. cholerae [ 286 ]. However, the emergence and evolution of toxigenic bacteria not only occurs in human or animal host environments but also in soil, aquatic, or plant environments under various selective pressures and genetic exchanges between bacterial populations and phages [ 278 ]. More enigmatic are the bacterial neurotoxins that recognize specific neuronal cells and target the specialized machinery of neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

“…Bacteria exploit various genetic mechanisms such as gene duplication, mutation, insertion/deletion, and recombination to generate novel or modified proteins. Toxin genes are located on diverse genetic support chromosomes, phages, plasmids, and transposons, which facilitate horizontal gene transfer between bacteria [ 161 , 278 ]. For example, 695 protein sequences have been identified for CDT subunits from at least 32 Gram-negative bacterial species.…”

Section: Insights Into the Evolution Of Bacterial Protein Toxinsmentioning

confidence: 99%

“…For optimal activity, bacterial toxins have acquired a modulable structure by differentiation, recombination, insertion, and/or deletion of specific domains (catalytic, translocation/delivery, autoprocessing, and receptor-binding domains) involved in the different steps of intoxication. For example, modular recombination has been documented for CNFs, Bordetella dermonecrotic toxins, and related toxins [ 278 ]. In C. difficile , the extensive diversification of TcdB seems to be mainly based on recombination events, with independent evolution of the four functional domains [ 281 , 282 ].…”

Section: Insights Into the Evolution Of Bacterial Protein Toxinsmentioning

confidence: 99%

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Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

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2024

Toxins

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Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based on size, structure, and mode of action. Upon recognition of a cell surface receptor (protein, glycoprotein, and glycolipid), they are active either at the cell surface (signal transduction, membrane damage by pore formation, or hydrolysis of membrane compound(s)) or intracellularly. Various bacterial protein toxins have the ability to enter cells, most often using an endocytosis mechanism, and to deliver the effector domain into the cytosol, where it interacts with an intracellular target(s). According to the nature of the intracellular target(s) and type of modification, various cellular effects are induced (cell death, homeostasis modification, cytoskeleton alteration, blockade of exocytosis, etc.). The various modes of action of bacterial protein toxins are illustrated with representative examples. Insights in toxin evolution are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Insights Into the Evolution Of Bacterial Protein Toxinsmentioning

confidence: 99%

Section: Insights Into the Evolution Of Bacterial Protein Toxinsmentioning

confidence: 99%

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Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

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2024

Toxins

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“…The cargo-delivery vehicles of these full-length CNF toxins share homology with the N-terminus of Pasteurella multocida toxin (PMT-N) ( 50 , 51 ), which can deliver not only its cargo but also other types of cargo ( 27 , 52 ). The CNF1-like catalytic domains have been found in many bacterial genomes associated with a wide range of different cargo-delivery systems ( 20 , 53 ). However, only a small number of these putative CNF1-like catalytic domain-containing proteins have been studied and confirmed to exhibit deamidase activity.…”

Section: Introductionmentioning

confidence: 99%

Hierarchical determinants in cytotoxic necrotizing factor (CNF) toxins driving Rho G-protein deamidation versus transglutamination

Handy,

Xu,

Moon

et al. 2024

mBio

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The cytotoxic necrotizing factor (CNF) family of AB-type bacterial protein toxins catalyze two types of modification on their Rho GTPase substrates: deamidation and transglutamination. It has been established that E. coli CNF1 and its close homolog proteins catalyze primarily deamidation and Bordetella dermonecrotic toxin (DNT) catalyzes primarily transglutamination. The rapidly expanding microbial genome sequencing data have revealed that there are at least 13 full-length variants of CNF1 homologs. CNFx from E. coli strain GN02091 is the most distant from all other members of the CNF family with 50%–55% sequence identity at the protein level and 0.45–0.52 nucleotide substitutions per site at the DNA level. CNFx modifies RhoA, Rac1, and Cdc42, and like CNF1, activates downstream SRE-dependent mitogenic signaling pathways in human HEK293T cells, but at a 1,000-fold higher EC 50 value. Unlike other previously characterized CNF toxins, CNFx modifies Rho proteins primarily through transglutamination, as evidenced by gel-shift assay and confirmed by MALDI mass spectral analysis, when coexpressed with Rho-protein substrates in E. coli BL21 cells or through direct treatment of HEK293T cells. A comparison of CNF1 and CNFx sequences identified two critical active-site residues corresponding to positions 832 and 862 in CNF1. Reciprocal site-specific mutations at these residues in each toxin revealed hierarchical rules that define the preference for deamidase versus a transglutaminase activity in CNFs. An additional unique Cys residue at the C-terminus of CNFx was also discovered to be critical for retarding cargo delivery. IMPORTANCE Cytotoxic necrotizing factor (CNF) toxins not only play important virulence roles in pathogenic E. coli and other bacterial pathogens, but CNF-like genes have also been found in an expanding number of genomes from clinical isolates. Harnessing the power of evolutionary relationships among the CNF toxins enabled the deciphering of the hierarchical active-site determinants that define whether they modify their Rho GTPase substrates through deamidation or transglutamination. With our finding that a distant CNF variant (CNFx) unlike other known CNFs predominantly transglutaminates its Rho GTPase substrates, the paradigm of “CNFs deamidate and DNTs transglutaminate” could finally be attributed to two critical amino acid residues within the active site other than the previously identified catalytic Cys-His dyad residues. The significance of our approach and research findings is that they can be applied to deciphering enzyme reaction determinants and substrate specificities for other bacterial proteins in the development of precision therapeutic strategies.

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Draft Genomes of Six Philippine Erwinia mallotivora Isolates: Comparative Genomics and Genome-Wide Analysis of Candidate Secreted Proteins

Waje

Lantican

Pathania³

et al. 2022

Curr Microbiol

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Evolutionary aspects of toxin-producing bacteria

Cited by 6 publications

References 375 publications

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution

Hierarchical determinants in cytotoxic necrotizing factor (CNF) toxins driving Rho G-protein deamidation versus transglutamination

Draft Genomes of Six Philippine Erwinia mallotivora Isolates: Comparative Genomics and Genome-Wide Analysis of Candidate Secreted Proteins

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