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Open AccessArticle

A High-Homology Region Provides the Possibility of Detecting β-Barrel Pore-Forming Toxins from Various Bacterial Species

by Alexey S. Nagel, Olesya S. Vetrova, Natalia V. Rudenko, Anna P. Karatovskaya, Anna V. Zamyatina, Zhanna I. Andreeva-Kovalevskaya, Vadim I. Salyamov, Nadezhda A. Egorova, Alexander V. Siunov, Tatiana D. Ivanova, Khanafi M. Boziev, Fedor A. Brovko and Alexander S. Solonin

Int. J. Mol. Sci. 2024, 25(10), 5327; https://doi.org/10.3390/ijms25105327 - 14 May 2024

Cited by 2 | Viewed by 1909

Abstract

The pathogenicity of many bacteria, including Bacillus cereus and Staphylococcus aureus, depends on pore-forming toxins (PFTs), which cause the lysis of host cells by forming pores in the membranes of eukaryotic cells. Bioinformatic analysis revealed a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus in over 600 PFTs, which we designated as a “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them—HlyII and cytotoxin K2 (CytK2)—are synthesized in Bacillus cereus sensu lato; the third, S. aureus α-toxin (Hla), is the most investigated representative of the family. Protein modeling showed certain amino acids of the homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide, DSFNTFYGNQLFMK, as part of the homologous peptide. The HlyII, CytK2, and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of this work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs. Full article

(This article belongs to the Collection Feature Papers in Molecular Immunology)

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21 pages, 1705 KB

Open AccessArticle

Comparative Structural Analysis of Different Mycobacteriophage-Derived Mycolylarabinogalactan Esterases (Lysin B)

by Ahmed H. Korany, Adel Abouhmad, Walid Bakeer, Tamer Essam, Magdy A. Amin, Rajni Hatti-Kaul and Tarek Dishisha

Biomolecules 2020, 10(1), 45; https://doi.org/10.3390/biom10010045 - 27 Dec 2019

Cited by 7 | Viewed by 5102

Abstract

Mycobacteriophage endolysins have emerged as a potential alternative to the current antimycobacterial agents. This study focuses on mycolylarabinogalactan hydrolase (LysB) enzymes of the α/β-hydrolase family, which disrupt the unique mycolic acid layer of mycobacterium cell wall. Multiple sequence alignment and structural analysis studies showed LysB-D29, the only enzyme with a solved three-dimensional structure, to share several common features with esterases (lacking lid domain) and lipases (acting on long chain lipids). Sequence and structural comparisons of 30 LysB homology models showed great variation in domain organizations and total protein length with major differences in the loop-5 motif harboring the catalytic histidine residue. Docking of different p-nitrophenyl ligands (C4-C18) to LysB-3D models revealed that the differences in length and residues of loop-5 contributed towards wide diversity of active site conformations (long tunnels, deep and superficial funnels, shallow bowls, and a narrow buried cave) resembling that of lipases, cutinases, and esterases. A set of seven LysB enzymes were recombinantly produced; their activity against p-nitrophenyl esters could be related to their active site conformation and acyl binding site. LysB-D29 (long tunnel) showed the highest activity with long chain p-nitrophenyl palmitate followed by LysB-Omega (shallow bowl) and LysB-Saal (deep funnel). Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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11 pages, 2102 KB

Open AccessArticle

Molecular Alterations in Dog Pheochromocytomas and Paragangliomas

by Esther Korpershoek, Daphne A. E. R. Dieduksman, Guy C. M. Grinwis, Michael J. Day, Claudia E. Reusch, Monika Hilbe, Federico Fracassi, Niels M. G. Krol, André G. Uitterlinden, Annelies de Klein, Bert Eussen, Hans Stoop, Ronald R. de Krijger, Sara Galac and Winand N. M. Dinjens

Cancers 2019, 11(5), 607; https://doi.org/10.3390/cancers11050607 - 30 Apr 2019

Cited by 20 | Viewed by 4603

Abstract

Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways. Full article

(This article belongs to the Special Issue Pheochromocytoma (PHEO) and Paraganglioma (PGL))

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