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.
The human population’s health, economy, and way of life have been seriously threatened by the Coronavirus Disease (COVID19) pandemic. Patients with cancer are one of the special patient groups who ...faced additional difficulties during COVID-19, with additional problems in their basket. To minimise the sufferings, regular physical activity of any intensity lowers the chance of cancer progression while enhancing survival rates and Quality of Life (QoL). The lengthy indoor stay during the COVID-19 lockdown prompted inactivity among cancer patients, reducing their overall QoL. The purpose of this article is to ascertain how COVID-19- related physical inactivity affected cancer patients and their QoL.
Our oral cavity reflects the inside of our body, i.e., a healthy mouth is directly associated with healthy body. Tongue is a muscular organ present in the floor of the oral cavity; involved in ...speech, chewing, carrying taste sensations, and deglutition. Tongue also plays a major role in identifying and diagnosing underlying systemic diseases. Therefore, a complete information regarding the examination, diagnosis, and management of tongue abnormalities become important. Tongue abnormalities can be seen at any age and therefore classified as developmental and acquired (inflammatory, infective, traumatic, environmental, autoimmune, and benign and malignant tumors). However, some common abnormalities of tongue in the case of children have not been described in literature yet. Hence, the present review will focus on the abnormities of tongue and their management in children along with presentation of some of the cases reported to the department.
epsilon toxin (Etx) is categorized as the third most lethal bioterrorism agent by the Centers for Disease Control and Prevention (CDC), with no therapeutic counter measures available for humans. ...Here, we have developed a high-affinity inhibitory compound by synthesizing and evaluating the structure activity relationship (SAR) of a library of diverse glycosides (numbered 1-12). SAR of glycoside-Etx heptamers revealed exceptionally strong H-bond interactions of glycoside-4 with a druggable pocket in the oligomerization and β-hairpin region of Etx. Analysis of its structure suggested that glycoside-4 might self-aggregate to form a robust micelle-like supra-molecular complex due to its linear side-chain architecture, which was authenticated by fluorescence spectroscopy. Further, this micelle hinders the Etx monomer-monomer interaction required for oligomerization, validated by both surface plasmon resonance (SPR) and immunoblotting. This phenomenon in turn leads to blockage of pore formation. Downstream evaluation revealed that glycoside-4 effectively blocked cell death of Etx-treated cultured primary cells and maintained cellular homeostasis via disrupting oligomerization, blocking pore formation, restoring calcium homeostasis, stabilizing the mitochondrial membrane and impairing high mobility group box 1 (HMGB1) translocation from nucleus to cytoplasm. Furthermore, a single dosage of glycoside-4 protected the Etx-challenged mice and restored normal function to multiple organs. This work reports for the first time a potent, nontoxic glycoside with strong ability to occlude toxin lethality, representing it as a bio-arm therapeutic against Etx-based biological threat.
Epsilon toxin (Etx) produced by
Clostridium perfringens
types B and D, a major causative agent of enterotoxaemia causes significant economic losses to animal industry. Conventional vaccines against ...these pathogens generally employ formalin-inactivated culture supernatants. However, immunization with the culture supernatant and full length toxin subjects the animal to antigenic load and often have adverse effect due to incomplete inactivation of the toxins. In the present study, an epitope-based vaccine against
Clostridium perfringens
Etx, comprising 40–62 amino acid residues of the toxin in translational fusion with heat labile enterotoxin B subunit (LTB) of
E. coli
, was evaluated for its protective potential. The ability of the fusion protein rLTB.Etx
40–62
to form pentamers and biologically active holotoxin with LTA of
E. coli
indicated that the LTB present in the fusion protein retained its biological activity. Antigenicity of both the components in the fusion protein was retained as anti-fusion protein antisera detected both the wild type Etx and LTB in Western blot analysis. Immunization of BALB/c mice with the fusion protein resulted in a significant increase in all isotypes, predominantly IgG1, IgG2a and IgG2b. Anti-fusion protein antisera neutralized the cytotoxicity of epsilon toxin both in vitro and in vivo. Thus, the results demonstrate the potential of rLTB.Etx
40–62
as a candidate vaccine against
C. perfringens
.
Interleukin-10, an important regulator of both the innate and adaptive immune systems, is a multifunctional major cytokine. Though it is one of the major cytokines, IL-10 from the Indian major carp, ...Labeo rohita, has not yet been characterized. In the present study, we report large scale production and purification of biologically active recombinant IL-10 of L. rohita (rLrIL-10) using a heterologous expression system and its biophysical and functional characterization. High yield (~70 mg/L) of soluble rLrIL-10 was obtained at shake flask level. The rLrIL-10 was found to exist as a dimer. Far-UV CD spectroscopy showed presence of predominantly alpha helices. The tertiary structure of the purified rLrIL-10 was verified by fluorescence spectroscopy. Two-dimensional gel analysis revealed the presence of six isoforms of the rLrIL-10. The rLrIL-10 was biologically active and its administration significantly reduced serum proinflammatory cytokines, namely, interleukin 1β, TNFα, and IL-8, and augmented the NKEF transcript levels in spleen of L. rohita. Anti-inflammatory role of the rLrIL-10 was further established by inhibition of phagocytosis using NBT reduction assay in vitro. The data indicate that the dimeric alpha helical structure and function of IL-10 of L. rohita as a key regulator of anti-inflammatory response have remained conserved during evolution.
With regard to literature available about international migration and different theorizations, they are not discussed much as they are hindered by the increasing diversification of migration ...typology. This paper reviews different theories of migration and talks about the need for an interdisciplinary approach to the study of international migration and its theorization. In the paper, the author provides an overview (personalized) of different theories of migration divided into sub-headings and structure. Theories of migration like Historical-structural theory, Push-pull theory, World system theory, Neoclassical theory, Political economy models, Role of network theory and Transnationalism or the 'transnational turn' are briefly discussed. It also points out some future challenges associated with theorization of migration. The study of migration in the global settings is restricted to socioeconomic and political aspects of the process of migration. The potential migrant's life, choices and reasons for relocation should be often discussed in the migration literature. Existential dimensions of migration and relevance of emotional aspect should be included while theorizing migration. Migration is a dynamic process with different dimensions attached to it. This paper is intended as a primer to understand some of the complexities of theorizing migration.
Zeta‐toxin is a cognate toxin of epsilon antitoxin of prokaryotic Type II toxin‐antitoxin system (TA) and play an important role in cell death. An orthologue of bacterial‐zeta‐toxin (BzT) was ...identified in Leishmania donovani with similar structural and functional features. Leishmania zeta‐toxin (named Ld_ζ1) harboring similar UNAG and ATP‐binding pockets showed UNAG kinase and ATP‐binding activity. An active Ld_ζ1 was found to express in infective extracellular promastigotes stage of L. donovani and episomal overexpression of an active Ld_ζ1domain‐triggered cell death. This study demonstrates the presence of prokaryotic‐like‐zeta‐toxin in eukaryotic parasite Leishmania and its association with cell death. Conceivably, phosphorylated UNAG or analogues, the biochemical mimics of zeta‐toxin function mediating cell death can act as a novel anti‐leishmanial chemotherapeutics.
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