Neutralization Of Bacterial Toxins Research Articles

New Strategies for Biocontrol of Bacterial Toxins and Virulence: Focusing on Quorum-Sensing Interference and Biofilm Inhibition.

The overuse of antibiotics and the emergence of multiple-antibiotic-resistant pathogens are becoming a serious threat to health security and the economy. Reducing antimicrobial resistance requires replacing antibiotic consumption with more biocontrol strategies to improve the immunity of animals and humans. Probiotics and medicinal plants have been used as alternative treatments or preventative therapies for a variety of diseases caused by bacterial infections. Therefore, we reviewed some of the anti-virulence and bacterial toxin-inhibiting strategies that are currently being developed; this review covers strategies focused on quenching pathogen quorum sensing (QS) systems, the disruption of biofilm formation and bacterial toxin neutralization. It highlights the probable mechanism of action for probiotics and medicinal plants. Although further research is needed before a definitive statement can be made on the efficacy of any of these interventions, the current literature offers new hope and a new tool in the arsenal in the fight against bacterial virulence factors and bacterial toxins.

Non-Digestible Oligosaccharides: A Novel Treatment for Respiratory Infections?

Emerging antimicrobial resistance in respiratory infections requires novel intervention strategies. Non-digestible oligosaccharides (NDOs) are a diverse group of carbohydrates with broad protective effects. In addition to promoting the colonization of beneficial gut microbiota and maintaining the intestinal homeostasis, NDOs act as decoy receptors, effectively blocking the attachment of pathogens on host cells. NDOs also function as a bacteriostatic agent, inhibiting the growth of specific pathogenic bacteria. Based on this fact, NDOs potentiate the actions of antimicrobial drugs. Therefore, there is an increasing interest in characterizing the anti-infective properties of NDOs. This focused review provides insights into the mechanisms by which representative NDOs may suppress respiratory infections by targeting pathogens and host cells. We summarized the most interesting mechanisms of NDOs, including maintenance of gut microbiota homeostasis, interference with TLR-mediated signaling, anti-oxidative effects and bacterial toxin neutralization, bacteriostatic and bactericidal effects, and anti-adhesion or anti-invasive properties. A detailed understanding of anti-infective mechanisms of NDOs against respiratory pathogens may contribute to the development of add-on therapy or alternatives to antimicrobials.

Antivirulence Therapy- A Promising Alternative Technique for Antibiotic Resistance

Antibiotic resistance is increasing at an alarming rate. Over the years there has been a steep rise in number of antibiotic resistant bacteria. This in turn has led to a dip in overall efficacy of a wide range of antibiotics. The last new class of antibiotics was introduced in 2003, but after that there has not been any significant discovery in this area. To overcome this problem of antibiotic resistance Antivirulence therapy has been introduced, this reduces pressure to discover new classes of antibiotics and improves efficacy of existing ones. It mainly focuses on preventing bacterial pathogenesis rather than having bactericidal effect. This overall reduces selective pressure on bacteria thus, slowing its mutation, leading to lower emergence of antibiotic resistance, as opposed to the conventional antibiotics. This review paper discusses various Antivirulence strategies like Quench Pathogen Quorum Sensing (QS) systems; disassemble of bacterial functional membrane microdomains (FMMs), disruption of biofilm formation and bacterial toxin neutralization. Keywords: Antivirulence therapy, QS systems, FMMs, Biofilm formation, Toxin neutralization. Cite this Article Dr.S.P.Zine, Ms. Ankita Rai, Mr. Parth Mehta, Ms. Sayli Sawant. Antivirulence Therapy- A Promising Alternative Technique for Antibiotic Resistance. Research & Reviews: A Journal of Bioinformatics . 2020; 7(3): 1–14p.

Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition.

Antimicrobial resistance constitutes one of the major challenges facing humanity in the Twenty-First century. The spread of resistant pathogens has been such that the possibility of returning to a pre-antibiotic era is real. In this scenario, innovative therapeutic strategies must be employed to restrict resistance. Among the innovative proposed strategies, anti-virulence therapy has been envisioned as a promising alternative for effective control of the emergence and spread of resistant pathogens. This review presents some of the anti-virulence strategies that are currently being developed, it will cover strategies focused on quench pathogen quorum sensing (QS) systems, disassemble of bacterial functional membrane microdomains (FMMs), disruption of biofilm formation and bacterial toxin neutralization.

Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane-Coated Nanosponges.

Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad-spectrum of hemolytic toxins regardless of their molecular structure. When tested with model pore-forming toxins, including melittin, α-hemolysin of methicillin-resistant Staphylococcus aureus, listeriolysin O of Listeria monocytogenes, and streptolysin O of Group A Streptococcus, the hRBC nanosponges are able to completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In addition, the nanosponge-detained toxins show no cytotoxicity when tested on human umbilical vein endothelial cells and no lethality when injected into mice, which together indicate effective toxin neutralization. Overall, these results demonstrate the broad applicability and high effectiveness of the hRBC nanosponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria.

Pharmacokinetic and Pharmacodynamic Considerations for the Use of Monoclonal Antibodies in the Treatment of Bacterial Infections

Antibiotic-resistant bacterial pathogens are increasingly implicated in hospital- and community-acquired infections. Recent advances in monoclonal antibody (mAb) production and engineering have led to renewed interest in the development of antibody-based therapies for treatment of drug-resistant bacterial infections. Currently, there are three antibacterial mAb products approved by the Food and Drug Administration (FDA) and at least nine mAbs are in clinical trials. Antibacterial mAbs are typically developed to kill bacteria or to attenuate bacterial pathological activity through neutralization of bacterial toxins and virulence factors. Antibodies exhibit distinct pharmacological mechanisms from traditional antimicrobials and, hence, cross-resistance between small molecule antimicrobials and antibacterial mAbs is unlikely. Additionally, the long biological half-lives typically found for mAbs may allow convenient dosing and vaccine-like prophylaxis from infection. However, the high affinity of mAbs and the involvement of the host immune system in their pharmacological actions may lead to complex and nonlinear pharmacokinetics and pharmacodynamics. In this review, we summarize the pharmacokinetics and pharmacodynamics of the FDA-approved antibacterial mAbs and those are currently in clinical trials. Challenges in the development of antibacterial mAbs are also discussed.

Lipoproteins attenuate TLR2 and TLR4 activation by bacteria and bacterial ligands with differences in affinity and kinetics.

BackgroundThe small intestine is a specialized compartment were close interactions take place between host, microbes, food antigens and dietary fatty acids. Dietary fats get absorbed by epithelial cells and processed into a range of lipoprotein particles after which they are basolaterally secreted and collected in the lymphatics. In contrast to the colon, the small intestine is covered only by a thin mucus coat that allows for intimate interactions between host-cells and microbes. Lipoproteins have long been recognized as protective factors in infectious diseases via the neutralization of bacterial toxins like lipopolysaccharides. Much less attention has been given to the potential role of lipoproteins as factors contributing to the maintenance of small intestinal immune homeostasis via modulating bacteria-induced immune responses.ResultsLipoproteins VLDL, LDL and HDL were found to neutralize TLR responses towards specific TLR-ligands or a selection of gram-negative and gram-positive bacteria. Attenuation of TLR2 activity was acute and only slightly improved by longer pre-incubation times of ligands and lipoproteins with no differences between bacterial-lipopeptides or bacteria. In contrast, attenuation of TLR4 responses was only observed after extensive preincubation of lipoproteins and LPS. Preincubation of bacteria and lipoproteins led only to a modest attenuation of TLR4 activity. Moreover, compared to TLR2, TLR4 activity could only be attenuated by lipoproteins over a small ligand dose range.ConclusionsThese results demonstrate the ability of lipoproteins VLDL, LDL and HDL to inhibit TLR responses towards bacterial-ligands and bacteria. Presence of lipoproteins was found to modulate the MAMP-induced cytokine release by primary human monocytes measured as changes in the release of IL-6, TNFα, GM-CSF and IFNγ. Using TLR2 and TLR4-reporter cells, lipoproteins were found to inhibit TLR responses with differences in affinity and kinetics. These data establish a role for lipoproteins as immunoregulatory molecules, attenuating TLR-responses and thereby positively contributing to mucosal homeostasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0180-x) contains supplementary material, which is available to authorized users.

Defensins: More than Nature�s Anti-bug Spray?

Human defensins were originally identified as natural antimicrobial peptides that protect the host from infections. More recently, novel biological functions of these peptides have been described, expanding their role as natural antimicrobials. Here, our current understanding of this expanding role of human α-defensins is reviewed, with emphasis on antibacterial killing, bacterial toxin neutralization and immunity.

Adrenal relationship to immunity

The question of the relationship of the endocrine glands, and in particular the adrenal glands, to immunity has not yet been finally resolved: while some authors recognize only the indirect importance of the endocrine organs in the fight against infection, given the extremely extensive biological role of these organs in the life of the animal body, others are inclined to seek a more direct relationship, allowing their participation or in the production of antithelials, or in the neutralization of bacterial toxins.