Histological Alterations in Some Organs of African Catfish (Clarias gariepinus) Exposed to Sub-lethal Concentrations of Glyphosate [N-(phosphonomethyl) glycine]

This study used a static bioassay to investigate the histological effects of glyphosate on the gill, liver and muscle of African catfish (Clarias gariepinus) fingerlings. This was done with a view of further characterising the effect of glyphosate on C. gariepinus fingerlings and other aquatic life forms. Six-week old C. gariepinus fingerlings with an average weight of 10.02 ± 0.2 g were stocked into three exposure sets (control, 2.75 ppm (25% of the 96 h LC50 value) and 5.50 ppm (50% of the 96 h LC50 value)) in triplicate at 30 fish per tank for 70 days. The 96 h LC50 value was 11.00 mg/L. Histological examination of the C. gariepinus exposed to various sublethal concentrations of glyphosate showed that major histological changes in their organs were concentration dependent such as gill arch vacuolation, excessive mucosal secretions, lifting of epithelial, and epithelium thickening, hyperplasia and telangiectasis in the gills, discolouration, change in form and consistent alterations involving hyperplasia, narrowing of the central nerve, necrosis, pkynosis, blood congestion and vacuolation of the liver, mild hyperplasia and inflammatory responses in the muscle of the fish. The severity of histological alteration was more pronounced in fish organs exposed to 5.50 ppm of glyphosate concentration. This study concluded that the toxicant (glyphosate) is highly toxic to C. gariepinus particularly at a concentration of 5.50 ppm, therefore its use near farm lands or adjacent water bodies should be discouraged.

Applications of Lysozyme, an Innate Immune Defense Factor, as an Alternative Antibiotic

Lysozyme is a ~14 kDa protein present in many mucosal secretions (tears, saliva, and mucus) and tissues of animals and plants, and plays an important role in the innate immunity, providing protection against bacteria, viruses, and fungi. Three main different types of lysozymes are known: the c-type (chicken or conventional type), the g-type (goose type), and the i-type (invertebrate type). It has long been the subject of several applications due to its antimicrobial properties. The problem of antibiotic resistance has stimulated the search for new molecules or new applications of known compounds. The use of lysozyme as an alternative antibiotic is the subject of this review, which covers the results published over the past two decades. This review is focused on the applications of lysozyme in medicine, (the treatment of infectious diseases, wound healing, and anti-biofilm), veterinary, feed, food preservation, and crop protection. It is available from a wide range of sources, in addition to the well-known chicken egg white, and its synergism with other compounds, endowed with antimicrobial activity, are also summarized. An overview of the modified lysozyme applications is provided in the form of tables.

Recombinant neutralizing secretory IgA antibodies for preventing mucosal carriage and transmission of SARS-CoV-2

Passive delivery of antibodies to mucosal sites might be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. However, monoclonal IgG antibody therapies, currently used for treatment of severe infections, are unlikely to prove useful in mucosal sites where SARS-CoV-2 resides and replicates in early infection. Here, we investigated the feasibility of producing neutralising monoclonal IgA antibodies against SARS-COV-2. We identified two class-switched mAbs that express well as monomeric and secretory IgA variants with retained antigen binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralisation activities than IgG mAbs and were able to reduce SARS-CoV-2 infection in an in vivo murine model. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Effect of Synergistic Action of Bovine Lactoferrin with Antibiotics on Drug Resistant Bacterial Pathogens

Background and Objectives: The multidrug resistant (MDR) bacterial pathogenic infection is one of the chief worldwide public health threat to humanity. The development of novel antibiotics against MDR Gram negative bacteria has reduced over the last half century. Research is in progress regarding the treatment strategies that could be engaged in combination with antibiotics to extend the duration of these life-saving antibacterial agents. The current study was therefore planned to assess the synergistic effects of bovine lactoferrin (bLF) in combination with different antibiotics that are conventionally used. This synergism would provide a newer therapeutic choice against MDR pathogens. LF is present in mucosal secretions, vastly in milk. LF is considered an important constituent in host defense. In previous reports, LF has been co-administered as a combination antibiotic therapy. Materials and Methods: This study included synergistic (LF + appropriate antibiotic) exposure against 147 locally encountered bacterial pathogens, which were completely characterized strains. The anti-biofilm effects and the outcome of bLF on minimum inhibitory concentrations (MICs) of antibacterials on clinical MDR bacterial pathogens were determined by standard techniques. Results: In our study, synergism of bLF with antibacterial agents were reproducible and found to be significant. LF on its own had an important effect of inhibiting the biofilm production of some significant bacterial pathogens. Conclusion: The results of this study provides useful data on the antibacterial potential of the combination of LF with antibiotics against drug resistant pathogens.

In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS, n = 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS, n = 5); and the positive for COVID-19 (COVID-19, n = 27). Higher specific-SIgA for SARS-CoV-2, IFN-β, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.

Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells

Secretory IgA (SIgA) is the dominant antibody class in mucosal secretions. The majority of plasma cells producing IgA are located within mucosal membranes lining the intestines. SIgA protects against the adhesion of pathogens and their penetration into the intestinal barrier. Moreover, SIgA regulates gut microbiota composition and provides intestinal homeostasis. In this review, we present mechanisms of SIgA generation: T cell-dependent and -independent; in different non-organized and organized lymphoid structures in intestinal lamina propria (i.e., Peyer’s patches and isolated lymphoid follicles). We also summarize recent advances in understanding of SIgA functions in intestinal mucosal secretions with focus on its role in regulating gut microbiota composition and generation of tolerogenic responses toward its members.

Structure of the Human Secretory Immunoglobulin M Core

Immunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through highly a conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.

A prospective on multiple biological activities of lactoferrin contributing into piglet welfare

Piglets, especially for weaning piglets, due to rapid growth, physiological immaturity and gradual reduction of maternal antibodies, showed a lower immunity level and higher morbidity, which affects seriously growth performance and economic benefits. It is important that the piglets are how to adapt to nutrient digestion and absorption, and to develop the intestinal function and the colonization of gut microbiota during early stage as soon as possible. Lactoferrin is a natural glycoprotein polypeptide that is differentiated from the transferrin family. It is widely found in mucosal secretions such as saliva and tears, and most highly in milk and colostrum. As a multifunctional bioactive protein and a recommended food additive, lactoferrin is a potential candidate of alternatives to antibiotics and health promoter additive in piglet nutrition and production，it is expected that lactoferrin as green additive would play its important role for health maintaining in pig production. The following actual effects would be reviewed and evaluated: improvement on the digestion and absorption capacity in intestinal tracts, promotion on iron supplementation and reduction of the incidence of iron deficiency anemia, regulation on intestinal function and microbial flora balance, and enhancement on the disease resistance of piglets as an immunomodulatory and enhancer.

Prolonged viability of SARS-CoV-2 in fomites

SARS-CoV-2 has spread worldwide, demonstrating a great potential for direct and indirect transmission between humans. Whether coronaviruses can keep their infectivity in fomites through remaining viable on dry surfaces for periods exceeding hours, as shown for SARS-CoV and MERS-CoV, remains debated (1). Whether this is also true for SARS-CoV-2 remains uncertain; specifically there is no data about the role of proteins on virus viability in the environment. We evaluated the stability and infectivity of SARS-CoV-2 deposited on polystyrene plastic, aluminum and glass for 96 hours at 45-55% relative humidity and 19-21°C temperature range using a 106 TCID50/mL inoculum; these experiments were conducted with and without bovine serum albumine (BSA, 10g/L) for mimicking the protein content (interfering substance) within body fluids of the respiratory system such as cough droplets, sputum, and airways mucosal secretions (2). Briefly, 50μL of virus was deposited on the various surfaces and recovered sequentially by adding 150µl of cell culture medium; infectiousness was immediately quantified by end-point titration on Vero E6 cells. Each experiment was replicated three times. The limit of detection was about 100.5 TCID50/mL. Regardless the type of surface, virus viability decreased of approximately one log10 within 2 hours; afterwards, three drastically different profiles were observed depending of surface type: (i) steady viability with a <1 log10 drop over 92 hours on polystyrene plastic, (ii) a 3.5 log10 decrease along 44 hours on glass, and (iii) a sharp 6 log10 drop in less than 4 hours on aluminum (3, 4). The probable adsorption of viral particles onto polystyrene surface was associated with prolonged viability, whereas the drastic drop on aluminum suggests an intrinsic virucidal activity of this metal (3). Interestingly, SARS-CoV-2 viability was remarkably preserved in the presence of BSA regardless the type of surface. The 10g/L BSA condition used in our study is closely mimicking respiratory fluids (mucus, airways secretions, sputum) possessing protein concentrations higher than 10g/L (2). This resembles what happens when a COVID-19 patient is coughing or depositing infected airways secretions on surfaces. In conclusions we showed that even moderate protein concentrations in droplets increased drastically the viability of SARS-CoV-2 as for other viruses (5). Accordingly, it is plausible that contaminated fomites containing viable SARS-CoV-2 play a significant role in the person-to-person dissemination. This supports surface cleaning as a necessary action to be enforced and repeated since it may play a key role in halting SARS-CoV-2 transmission and mitigating the COVID-19 pandemic.