Protective potency of recombinant meningococcal IgA1 protease and its structural derivatives upon animal invasion with meningococcal and pneumococcal infections

Kotel’nikova, O. V.; Alliluev, A. P.; Zinchenko, Anatoly; Zhigis, L. S.; Prokopenko, Yuri; Nokel, E. A.; Razgulyaeva, O. A.; Zueva, V. S.; Tokarskaya, M. M.; Yastrebova, Natalia; Гордеева, Е. А.; Melikhova, T. D.; Kaliberda, E. N.; Румш, Л. Д.

doi:10.1016/j.micinf.2019.02.003

Cited by 7 publications

(8 citation statements)

References 19 publications

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“…This result indirectly indicates that the proteins' translocation directed by YSIRK-G/S indeed contributes to bacteria-host interaction and evasion from host immune clearance by exporting specific cell wall anchoring effectors. Further analysis has determined that the biological functions of numerous cell wall anchoring effectors have been clarified, such as the IgA1 protease of S. suis, S. pneumoniae and Neisseria meningitidis for IgA degradation [53], M-like protein SzM of S. equi for antibody binding [9], and IgG endopeptidase Mac of S. pyogenes and S. equi for IgG degradation [54,55]. These observations imply that cell wall anchoring effectors delivered through YSIRK-G/ S-directed translocation play vital roles in the pathogenic processes of Gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Amongst the retrieved cell wall anchoring effectors (Table S3), the glycosyl hydrolase and peptidase encoding proteins should be more deeply explored. The several proteins from these two types have been confirmed to play significant functions in both bacteria-host interaction and pathogenic processes, such as Endo-β-N-acetylglucosaminidases [5][6][7], C5a peptidases [21], IgA1 protease [53]. In particular, the three encoded domains of potential effectors, including GH_101_like N-acetyl-α-hexosaminidase, Chb N-acetyl-βhexosaminidase and GH20_hexosaminidase, were predicted to portray similar enzymic activities to the Endoβ-N-acetylglucosaminidase homologs, thus suggesting their potential roles during bacterial infection.…”

Section: Disclosure Statementmentioning

confidence: 99%

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YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

Bai

Zhang

et al. 2020

Virulence

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The Streptococcus suis serotype 2 (SS2) is a significant zoonotic pathogen that is responsible for various swine diseases, even causing cytokine storms of Streptococcal toxic shock-like syndromes amongst human. Cell wall anchoring proteins with a C-terminal LPxTG are considered to play vital roles during SS2 infection; however, their exporting mechanism across cytoplasmic membranes has remained vague. This study found that YSIRK-G/S was involved in the exportation of LPxTGanchoring virulence factors MRP and SspA in virulent SS2 strain ZY05719. The whole-genome analysis indicated that diverse LPxTG proteins fused with an N-terminal YSIRK-G/S motif are encoded in strain ZY05719. Two novel LPxTG proteins SspB and YzpA were verified to be exported via a putative transport system that was dependent on the YSIRK-G/S directed translocation, and portrayed vital functions during the infection of SS2 strain ZY05719. Instead of exhibiting an inactivation of C5a peptidase in SspB, another LPxTG protein with an N-terminal YSIRK-G/S motif from Streptococcus agalactiae was depicted to cleave the C5a component of the host complement. The consequent domain-architecture retrieval determined more than 10,000 SspB/YzpA like proteins that are extensively distributed in the Gram-positive bacteria, and most of them harbor diverse glycosyl hydrolase or peptidase domains within their middle regions, thus presenting their capability to interact with host cells. The said findings provide compelling evidence that LPxTG proteins with an N-terminal YSIRK-G/S motif are polymorphic effectors secreted by Gram-positive bacteria, which can be further proposed to define as cell wall anchoring effectors in a new subset.

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Section: Discussionmentioning

confidence: 99%

Section: Disclosure Statementmentioning

confidence: 99%

YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

Bai

Zhang

et al. 2020

Virulence

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“…Experimental confirmation of the protective activity of IgA1 protease is shown in a small number of works. In a series of works [64][65][66][67][68][69][70][71][72][73][74] in animal experiments, it was shown that native IgA1 protease isolated from a live virulent culture of N. meningitidis serogroup A, as well as recombinant IgA1 proteases of N. meningitidis serogroup B in active or mutant forms, and some truncated analogs of these proteins have high immunogenic and protective activity.…”

Section: Iga1 Protease and Its Fragments As A Basis For The Creation Of Therapeutic And Preventive Agentsmentioning

confidence: 99%

“…On the example of individual low-molecularweight fragments of IgA1 protease, an important role of B and T epitopes located in the N-terminal region of IgA1 protease of N. meningitidis serogroup B (strain H44/76) for the preservation of immunogenic and protective properties was demonstrated [64,65]. These proteins protected mice from infection with a live virulent culture of meningococci of the main epidemic serogroups (A, B, and C) and had the characteristic ability of proteins to form immunological memory [68,69,73].…”

Section: Iga1 Protease and Its Fragments As A Basis For The Creation Of Therapeutic And Preventive Agentsmentioning

confidence: 99%

“…Later Kotelnikova et al [68] found that immunization of animals with IgA1 protease of N. meningitidis and its analogs is capable of providing the formation of immunological memory and protection from fatal contagion not only with meningococcal, but also with pneumococcal infections. In contrast, the sera of rabbits immunized with the killed S. pneumoniae culture contained high titers of protective antibodies to IgA1 protease of N. meningitidis and its fragments.…”

Section: Iga1 Protease and Its Fragments As A Basis For The Creation Of Therapeutic And Preventive Agentsmentioning

confidence: 99%

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IgA1 Protease as a Vaccine Basis for Prevention of Bacterial Meningitis

et al. 2021

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The review covers the study of the protective properties of IgA1 protease and the possibility of creating a vaccine preparation for the prevention of bacterial meningitis of various origins on its basis. Bacterial meningitis belongs to the group of socially dangerous diseases and is characterized by a severe course, numerous complications and high mortality. The approaches used at present in world practice to create antimicrobial vaccines are based on a narrow targeting against a specific pathogen. The development of a monocomponent vaccine against a wide range of bacterial pathogens with a common virulence factor is still relevant. IgA1 protease, a protein that is one of the main virulence factors of a number of gram-negative and gram-positive bacteria, can serve as such an antigen. Bacterial IgA1 protease is uniquely specific for immunoglobulins A1 (IgA1), cleaving peptide bonds in the hinge regions of the IgA1 in humans and other higher primates. Bacteria, getting on the mucous membrane, destroy IgA1, which acts as the first barrier to protect the body from infections. Neutralization of IgA1 protease at this stage can become an obstacle to the development of infection, hindering the adhesion of a number of pathogens that produce this protein. The data available in the literature on the mechanism of antibacterial protection are scattered and ambiguous. The review considers the literature data and the results of our own experiments on the protective activity of IgA1 protease. We have shown that the recombinant meningococcal IgA1 protease and some of its fragments protect mice from infection with a live virulent culture not only of meningococci of the main epidemic serogroups (A, B, C, and W135), but also of some of the most common virulent pneumococcal serotypes. The data obtained indicate the possibility of creating a monocomponent vaccine against these and, possibly, other bacterial infections. Currently, significant progress has been made in studying the structure and functions of secreted proteins in the bacteria Neisseria meningitidis and Haemophilus influenzae. In this review we describe protein translocation systems of N. meningitidis, which are related to the secretion of proteins in these bacteria, and also present modern data on the functions of these proteins. Analysis of experimental data on the structure of IgA1 protease of N. meningitidis and the formation of immunity during vaccination is of key importance in the development of prophylactic preparations.

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Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

Mehanny

Kroniger

Koch

et al. 2021

Adv Healthcare Materials

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Streptococcus pneumoniae infections are a leading cause of death worldwide. Bacterial membrane vesicles (MVs) are promising vaccine candidates because of the antigenic components of their parent microorganisms. Pneumococcal MVs exhibit low toxicity towards several cell lines, but their clinical translation requires a high yield and strong immunogenic effects without compromising immune cell viability. MVs are isolated during either the stationary phase (24 h) or death phase (48 h), and their yields, immunogenicity and cytotoxicity in human primary macrophages and dendritic cells have been investigated. Death-phase vesicles showed higher yields than stationary-phase vesicles. Both vesicle types displayed acceptable compatibility with primary immune cells and several cell lines. Both vesicle types showed comparable uptake and enhanced release of the inflammatory cytokines, tumor necrosis factor and interleukin-6, from human primary immune cells. Proteomic analysis revealed similarities in vesicular immunogenic proteins such as pneumolysin, pneumococcal surface protein A, and IgA1 protease in both vesicle types, but stationary-phase MVs showed significantly lower autolysin levels than death-phase MVs. Although death-phase vesicles produced higher yields, they lacked superiority to stationary-phase vesicles as vaccine candidates owing to their similar antigenic protein cargo and comparable uptake into primary human immune cells.

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Protective potency of recombinant meningococcal IgA1 protease and its structural derivatives upon animal invasion with meningococcal and pneumococcal infections

Cited by 7 publications

References 19 publications

YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

YSIRK-G/S-directed translocation is required for Streptococcus suis to deliver diverse cell wall anchoring effectors contributing to bacterial pathogenicity

IgA1 Protease as a Vaccine Basis for Prevention of Bacterial Meningitis

Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

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