Multifunctionality and intrinsic disorder of royal jelly proteome.

Royal Jelly (RJ) is a gelatinous white-yellowish fluid, possessing a sour taste and a slight phenolic smell that is secreted by the hypopharyngeal and mandibular salivary glands of the nurse honeybees, and is used in nutrition of larvae and adult queens. Similar to other substances associated with the activities of honeybees, RJ not only contains nutritive components, such as carbohydrates, proteins, peptides, lipids, vitamins, and mineral salts, but also represents a natural ingredient with cosmetic and health-promoting properties. RJ is characterized by remarkable multifunctionality, possessing numerous biological activities. Although this multifunctionality of RJ can be considered as a consequence of its complex nature, many proteins and peptides in RJ are polyfunctional entities themselves. In this article, we show that RJ proteins contain different levels of intrinsic disorder, have sites of post-translational modifications, can be found in multiple isoforms, and many of them possess disorder-based binding sites, suggesting that the conformational ensembles of the RJ proteins might undergo change as a result of their interaction with specific binding partners. All these observations suggest that the multifunctionality of proteins and peptides from RJ is determined by their structural heterogeneity and polymorphism, and serve as an illustration of the protein structure-function continuum concept.

Human Salmonellosis: A Continuous Global Threat in the Farm-to-Fork Food Safety Continuum.

Salmonella is one of the most common zoonotic foodborne pathogens and a worldwide public health threat. Salmonella enterica is the most pathogenic among Salmonella species, comprising over 2500 serovars. It causes typhoid fever and gastroenteritis, and the serovars responsible for the later disease are known as non-typhoidal Salmonella (NTS). Salmonella transmission to humans happens along the farm-to-fork continuum via contaminated animal- and plant-derived foods, including poultry, eggs, fish, pork, beef, vegetables, fruits, nuts, and flour. Several virulence factors have been recognized to play a vital role in attaching, invading, and evading the host defense system. These factors include capsule, adhesion proteins, flagella, plasmids, and type III secretion systems that are encoded on the Salmonella pathogenicity islands. The increased global prevalence of NTS serovars in recent years indicates that the control approaches centered on alleviating the food animals' contamination along the food chain have been unsuccessful. Moreover, the emergence of antibiotic-resistant Salmonella variants suggests a potential food safety crisis. This review summarizes the current state of the knowledge on the nomenclature, microbiological features, virulence factors, and the mechanism of antimicrobial resistance of Salmonella. Furthermore, it provides insights into the pathogenesis and epidemiology of Salmonella infections. The recent outbreaks of salmonellosis reported in different clinical settings and geographical regions, including Africa, the Middle East and North Africa, Latin America, Europe, and the USA in the farm-to-fork continuum, are also highlighted.

In Vitro Exploration of the Anti-HCV Potential of the Synthetic Spacer Peptides Derived from Human, Bovine, and Camel Lactoferrins.

BACKGROUND: Chronic liver disease is often associated with the infection by hepatitis C virus (HCV), which is an enveloped RNA virus belonging to the Flaviviridae family. Many studies found that milk proteins, such as lactoferrin, might have profound antiviral activity against HCV. Various secretory fluids ranging from milk, to tears, saliva, and nasal secretion, and to bile and pancreatic juice, as well as neutrophils, mucosal surfaces, and blood contain a widely spread multifunctional glycoprotein, lactoferrin (Lf), structure of which can be depicted as two homologous domains connected by the short spacer peptide. OBJECTIVE: This study aimed to understand the effectiveness of the synthetic peptides cLfsp, bLfsp, hLfsp1, and hLfsp2 corresponding to the spacer peptides of camel, bovine, and human Lfs, respectively, against HCV in in vitro settings. METHOD: We used RT-nested PCR to evaluate the antiviral activity of the synthesized spacer peptides against HCV infectivity in PBMC and HepG2 cells looking at their neutralization, protection, and intracellular treatment potentials. RESULTS AND CONCLUSION: We show that direct interaction of hLfsp1, hLfsp2, and bLfsp with viral particles is able to neutralize the HCV entry into HepG2 cells (with hLfsp2 being more potent neutralizer than hLfsp1 and bLfsp), whereas cLfsp does not show any neutralizing potential. Therefore, our analysis revealed that different spacer peptides are characterized by different antiviral potentials and use different mechanisms for antiviral protection.

Structural heterogeneity and multifunctionality of lactoferrin.

Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities. This multifunctionality is determined by the fact that lactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions. Structurally, lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes. These lobes are unevenly glycosylated (with the C-lobe typically containing more N-linked glycosylation sites). Each lobe can bind a single ferric ion concomitantly with one bicarbonate anion. Lactoferrin and its lobes have a wide spectrum of antimicrobial and antiviral activities, with the antimicrobial and antiviral potentials dependent on the type of microbes and viruses. Often, the N-lobe possesses the majority of antimicrobial activities. In addition, lactoferrin and its lobes possess clear anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities.