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Applied Microbiology and Biotechnology Mar 2021Almost all bacteria synthesize two types of toxins-one for its survival by regulating different cellular processes and another as a strategy to interact with host cells... (Review)
Review
Almost all bacteria synthesize two types of toxins-one for its survival by regulating different cellular processes and another as a strategy to interact with host cells for pathogenesis. Usually, "bacterial toxins" are contemplated as virulence factors that harm the host organism. However, toxins produced by bacteria, as a survival strategy against the host, also hamper its cellular processes. To overcome this, the bacteria have evolved with the production of a molecule, referred to as antitoxin, to negate the deleterious effect of the toxin against itself. The toxin and antitoxins are encoded by a two-component toxin-antitoxin (TA) system. The antitoxin, a protein or RNA, sequesters the toxins of the TA system for neutralization within the bacterial cell. In this review, we have described different TA systems of bacteria and their potential medical and biotechnological applications. It is of interest to note that while bacterial toxin-antitoxin systems have been well studied, the TA system in unicellular eukaryotes, though predicted by the investigators, have never been paid the desired attention. In the present review, we have also touched upon the TA system of eukaryotes identified to date. KEY POINTS: Bacterial toxins harm the host and also affect the bacterial cellular processes. The antitoxin produced by bacteria protect it from the toxin's harmful effects. The toxin-antitoxin systems can be targeted for various medical applications.
Topics: Antitoxins; Bacteria; Bacterial Proteins; Bacterial Toxins; Toxin-Antitoxin Systems
PubMed: 33582835
DOI: 10.1007/s00253-021-11134-z -
Parasite Immunology Jul 2020Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic... (Review)
Review
Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.
Topics: Animals; Antibodies, Helminth; Antibody Formation; Ascariasis; Ascaris lumbricoides; Ascaris suum; Chemokine CCL24; Eosinophils; Humans; Immune Sera; Larva; Leukocyte Count; Macrophages; Mice; Swine; Swine Diseases; Vaccines
PubMed: 32394439
DOI: 10.1111/pim.12728 -
FEMS Microbiology Reviews Sep 2023Toxin-antitoxin (TA) systems are entities found in the prokaryotic genomes, with eight reported types. Type II, the best characterized, is comprised of two genes...
Toxin-antitoxin (TA) systems are entities found in the prokaryotic genomes, with eight reported types. Type II, the best characterized, is comprised of two genes organized as an operon. Whereas toxins impair growth, the cognate antitoxin neutralizes its activity. TAs appeared to be involved in plasmid maintenance, persistence, virulence, and defence against bacteriophages. Most Type II toxins target the bacterial translational machinery. They seem to be antecessors of Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) RNases, minimal nucleotidyltransferase domains, or CRISPR-Cas systems. A total of four TAs encoded by Streptococcus pneumoniae, RelBE, YefMYoeB, Phd-Doc, and HicAB, belong to HEPN-RNases. The fifth is represented by PezAT/Epsilon-Zeta. PezT/Zeta toxins phosphorylate the peptidoglycan precursors, thereby blocking cell wall synthesis. We explore the body of knowledge (facts) and hypotheses procured for Type II TAs and analyse the data accumulated on the PezAT family. Bioinformatics analyses showed that homologues of PezT/Zeta toxin are abundantly distributed among 14 bacterial phyla mostly in Proteobacteria (48%), Firmicutes (27%), and Actinobacteria (18%), showing the widespread distribution of this TA. The pezAT locus was found to be mainly chromosomally encoded whereas its homologue, the tripartite omega-epsilon-zeta locus, was found mostly on plasmids. We found several orphan pezT/zeta toxins, unaccompanied by a cognate antitoxin.
Topics: Antitoxins; Bacterial Toxins; Bacteria; Operon; Prokaryotic Cells; Bacterial Proteins
PubMed: 37715317
DOI: 10.1093/femsre/fuad052 -
Poultry Science May 2023Epidemiologic investigations in recent years have shown that the detection rate of avian hepatitis E virus (HEV) in chicken flocks is increasing in China. Nevertheless,...
Epidemiologic investigations in recent years have shown that the detection rate of avian hepatitis E virus (HEV) in chicken flocks is increasing in China. Nevertheless, effective prevention and control measures are still lacking. In this study, specific pathogen-free (SPF) chicken serum against HEV was prepared using recombinant HEV open reading frames (ORF2 and ORF3) proteins as immunogens. An SPF chicken infection model was established by intravenous inoculation of chick embryos. Swab samples were collected at 7, 14, 21, and 28 d of age and used to detect avian HEV load, along with other indicators, by fluorescence quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) assay. The therapeutic effects on blocking vertical HEV transmission were observed, by using the methods of antibody application alone, mixed, or combined application of each of the 2 antibodies with type I interferon. The results showed that type I interferon alone or in combination with antiserum reduced the positive rate of HEV from 100 to 62.5% and 25%, respectively. However, the avian HEV-positivity rate was reduced to 75, 50, and 37.5% after type I interferon was used alone or in combination with antisera against ORF2 and ORF3, respectively. The inhibitory effect of type I interferon alone or in combination with an antiserum, on HEV replication was more significant in cells than in vivo. In this study, the inhibitory effect of type I interferon alone or in combination with an antiserum on avian HEV replication was observed in vitro and in vivo, providing the necessary technical reserve for disease prevention and control.
Topics: Chick Embryo; Animals; Hepevirus; Chickens; Immunoglobulins; Immune Sera; Interferon Type I
PubMed: 36966643
DOI: 10.1016/j.psj.2023.102591 -
Virology Journal Nov 2023Intrinsic fitness costs are likely to have guided the selection of lineage-determining mutations during emergence of variants of SARS-CoV-2. Whereas changes in receptor...
Characterization of intrinsic and effective fitness changes caused by temporarily fixed mutations in the SARS-CoV-2 spike E484 epitope and identification of an epistatic precondition for the evolution of E484A in variant Omicron.
BACKGROUND
Intrinsic fitness costs are likely to have guided the selection of lineage-determining mutations during emergence of variants of SARS-CoV-2. Whereas changes in receptor affinity and antibody neutralization have been thoroughly mapped for individual mutations in spike, their influence on intrinsic replicative fitness remains understudied.
METHODS
We analyzed mutations in immunodominant spike epitope E484 that became temporarily fixed over the pandemic. We engineered the resulting immune escape mutations E484K, -A, and -Q in recombinant SARS-CoV-2. We characterized viral replication, entry, and competitive fitness with and without immune serum from humans with defined exposure/vaccination history and hamsters monospecifically infected with the E484K variant. We additionally engineered a virus containing the Omicron signature mutations N501Y and Q498R that were predicted to epistatically enhance receptor binding.
RESULTS
Multistep growth kinetics in Vero-, Calu-3, and NCI-H1299 were identical between viruses. Synchronized entry experiments based on cold absorption and temperature shift identified only an insignificant trend toward faster entry of the E484K variant. Competitive passage experiments revealed clear replicative fitness differences. In absence of immune serum, E484A and E484Q, but not E484K, were replaced by wildtype (WT) in competition assays. In presence of immune serum, all three mutants outcompeted WT. Decreased E484A fitness levels were over-compensated for by N501Y and Q498R, identifying a putative Omicron founder background that exceeds the intrinsic and effective fitness of WT and matches that of E484K. Critically, the E484A/Q498R/N501Y mutant and E484K have equal fitness also in presence of pre-Omicron vaccinee serum, whereas the fitness gain by E484K is lost in the presence of serum raised against the E484K variant in hamsters.
CONCLUSIONS
The emergence of E484A and E484Q prior to widespread population immunity may have been limited by fitness costs. In populations already exposed to the early immune escape epitope E484K, the Omicron founder background may have provided a basis for alternative immune escape evolution via E484A. Studies of major antigenic epitope changes with and without their epistatic context help reconstruct the sequential adjustments of intrinsic fitness versus neutralization escape during the evolution of major SARS-CoV-2 variants in an increasingly immune human population.
Topics: Animals; Cricetinae; Humans; Epitopes; SARS-CoV-2; COVID-19; Mutation; Immune Sera; Immunodominant Epitopes; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing
PubMed: 37940989
DOI: 10.1186/s12985-023-02154-4 -
Blood Sep 2019
Topics: Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Humans; Unrelated Donors
PubMed: 31515227
DOI: 10.1182/blood.2019002284 -
Toxicon : Official Journal of the... Mar 2022α-conotoxin (α-CTX) MI is a small peptide toxin with 14 amino acids and two disulfide bonds. It potently inhibits muscle-type nicotinic acetylcholine receptors...
α-conotoxin (α-CTX) MI is a small peptide toxin with 14 amino acids and two disulfide bonds. It potently inhibits muscle-type nicotinic acetylcholine receptors (nAChRs), and poses a threat as a toxin to tropical fishermen. However, there are currently no effective drugs for the treatment of MI envenomation due to the toxin's low immunogenicity. In this report, we generated neutralizing antiserum and F(ab') to MI by synthesizing a new MI antigen through the coupling of alkynyl-modified MI and azide-modified bovine serum albumin (BSA), followed by immunization into mouse and horse. The new MI-BSA antigen generated high titers of mouse and horse antiserum (1:204,800 and 1:51,200, respectively), and both the antiserum as well as the horse F(ab') displayed highly potent neutralization and detoxification efficacy. 12.5 μL of mouse or horse antiserum preincubated with MI could completely neutralize a lethal dose of the MI (0.4 μg, 1.7 × LD), while 6.25 μL (mouse) or 10.41 μL (horse) of the antiserum could exert complete detoxification of mice injected with 1.7 × LD of MI. Moreover, the mouse and horse antiserum exhibited medium cross-reactivity for highly toxic α-CTX GI. These results demonstrate that the integrity of MI's antigen epitope and carrier effect of BSA can improve MI's immunogenicity, and provides an effective detoxification treatment for highly toxic α-conotoxins as well as an effective method for the preparation of antiserum of small peptide toxins.
Topics: Animals; Conotoxins; Horses; Immune Sera; Nicotinic Antagonists; Peptides; Receptors, Nicotinic
PubMed: 35104533
DOI: 10.1016/j.toxicon.2022.01.009 -
Emergency Medicine Australasia : EMA Aug 2019
Topics: Animals; Antivenins; Australia; Elapidae; Humans; Snake Bites; Victoria
PubMed: 31313488
DOI: 10.1111/1742-6723.13337 -
Nature Biotechnology Nov 2020
Topics: Animals; Antibodies; Antibodies, Monoclonal; Immune Sera; Immunity; Immunization; Social Control, Formal
PubMed: 33046876
DOI: 10.1038/s41587-020-0687-9 -
European Review For Medical and... Sep 2022Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone... (Review)
Review
OBJECTIVE
Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of pre-analytical, analytical, and post-analytical phases.
QUALITATIVE AND QUANTITATIVE METHODS
The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis performed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for increased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP.
CONCLUSIONS
The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.
Topics: Bence Jones Protein; Humans; Immune Sera; Immunoglobulin Light Chains; Neoplasms; Paraproteinemias; Proteinuria
PubMed: 36196726
DOI: 10.26355/eurrev_202209_29779