[Show abstract][Hide abstract] ABSTRACT: Staphylococcal enterotoxin B (SEB) of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific V regions of T-cell receptors (TCR) and major histocompatibility complex (MHC) class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes / macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. Because of superantigen-induced T cells skewed towards TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR / MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFκB and the phosphoinositide 3-kinase / mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an “SEB-only” model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA / RNA sensors, apoptosis / DNA damage-related molecules, immunoproteasome components, as well as anti-viral and IFN-stimulated genes. The host-wide induction of these, and other, anti-microbial defense genes provide evidence that SEB elicits danger signals resulting in multi-organ damage and toxic shock. Ultimately, these discoveries might lead to novel therapeutics for various superantigen-based diseases.
Preview · Article · Feb 2016 · Frontiers in Immunology
[Show abstract][Hide abstract] ABSTRACT: Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism
threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model
were investigated using whole-genome microarrays. Gene expression profiles were compared between infected
THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential up regulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the toll like receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.
Full-text · Article · Nov 2015 · Current Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become a rising threat to public health. There is an urgent need for development of promising new therapeutic agents against drug resistant bacteria like S. aureus. This report discusses purification and characterization of proteins from Indian Russell’s viper snake venom. Novel 15-kDa proteins called “Viperatoxin” (VipTx-I and VipTx-II) were extracted from the whole venom and evaluated using in vitro antimicrobial experiments. The N-terminal amino acid sequence of “Viperatoxin” showed high sequence homology to daboiatoxin isolated from the same venom and also matched to phospholipase A2 (PLA2) enzymes isolated from other snake venoms. In an in vitro plate assay, VipTx-II but not VipTx-I showed strong antimicrobial effects against S. aureus and Burkholderia pseudomallei (KHW & TES), Proteus vulgaris and P. mirabilis. The VipTx-II was further tested by a broth-dilution assay at 100–3.1μg/ml concentrations. The most potent bactericidal effect was found at the lowest dilutions (MICs of 6.25μg/ml) against B. pseudomallei, S. aureus and P. vulgaris (MICs of 12.25μg/ml). Electron microscopic investigation revealed that the protein-induced bactericidal potency was closely associated with pore formation and membrane damage, even at the lowest concentrations (<20μg/ml). The toxin caused a low level of cytotoxic effects as observed in human (THP-1) cells at higher concentrations. Molecular weight determinations of VipTx-II by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one major, along with few minor bands. The results indicate that VipTx-II plays a significant role in bactericidal and membrane damaging effects in vitro. Non-cytotoxic properties on human cells highlight it as a promising candidate for further evaluation for its antimicrobial potential in vivo.
[Show abstract][Hide abstract] ABSTRACT: Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin.
[Show abstract][Hide abstract] ABSTRACT: Background
Translational exploration of bacterial toxins has come to the forefront of research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds to CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently demonstrated that LSR expression correlates with estrogen receptor positive breast cancers and that LSR signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify the mechanisms of iota toxin cytotoxicity in a tissue-specific, breast cancer model with the ultimate goal of laying the foundation for using iota toxin as a targeted breast cancer therapy.
In vitro model systems were used to determine the cytotoxic effect of iota toxin on breast cancer intrinsic subtypes. The use of overexpression and knockdown technologies confirmed the roles of LSR and CD44 in regulating iota toxin endocytosis and induction of cell death. Lastly, cytotoxicity assays were used to demonstrate the effect of iota toxin on a validated set of tamoxifen resistant breast cancer cell lines.
Treatment of 14 breast cancer cell lines revealed that LSR+/CD44- lines were highly sensitive, LSR+/CD44+ lines were slightly sensitive, and LSR-/CD44+ lines were resistant to iota cytotoxicity. Reduction in LSR expression resulted in a significant decrease in toxin sensitivity; however, overexpression of CD44 conveyed toxin resistance. CD44 overexpression was correlated with decreased toxin-stimulated lysosome formation and decreased cytosolic levels of iota toxin. These findings indicated that expression of CD44 drives iota toxin resistance through inhibition of endocytosis in breast cancer cells, a role not previously defined for CD44. Moreover, tamoxifen-resistant breast cancer cells exhibited robust expression of LSR and were highly sensitive to iota-induced cytotoxicity.
Collectively, these data are the first to show that iota toxin has the potential to be an effective, targeted therapy for breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Infectious diseases are a significant cause of morbidity and mortality worldwide, accounting for approximately 50% of all deaths in tropical countries and as much as 20% of deaths in the USA. The emergence of multi-drug resistant (MDR) strains makes the risk of these infections even more threatening and an important public health problem thereby increasing need of new agents for fighting pathogens. In this review, the remarkable antibacterial properties possessed by various snake venoms (Crotalide, Elapidae, and Viperidae families) were discussed and in particular phospholipase A2s (PLA2s) that have emerged from various studies as potential in the last few years. Group IIA PLA2s are the most potent among the snake venom (sv)PLA2s against various types of bacteria. Further, antibacterial derivatives from PLA2s, e.g. peptides derived from the C-terminal sequence of Lys49-PLA2s (amino acids 115-129), kill bacteria and cause severe membrane-damaging effects. Mechanisms of binding to the bacterial surface and subsequent killing by peptides are based on positive charge, hydrophobicity, and length. These peptide candidates are easy to design and synthesize in pure form (~95% purity). Such peptides may be potentially useful in the clinic as new antimicrobials for combating infections due to antibiotic-resistant bacteria that include methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus in the near future.
Full-text · Article · May 2014 · Mini-Reviews in Organic Chemistry
[Show abstract][Hide abstract] ABSTRACT: Basic phospholipase A2 was identified from the venom of the eastern diamondback rattlesnake. The Crotalus adamanteus toxin-II (CaTx-II) induced bactericidal effects (7.8 µg/ml) on Staphylococcus aureus, while on Burkholderia pseudomallei (KHW), and Enterobacter aerogenes were killed at 15.6 µg/ml. CaTx-II caused pore formation and membrane damaging effects on the bacterial cell wall. CaTx-II was not cytotoxic on lung (MRC-5), skin fibroblast (HEPK) cells and in mice. CaTx-II-treated mice showed significant wound closure and complete healing by 16 days as compared to untreated controls (**P<0.01). Histological examination revealed enhanced collagen synthesis and neovascularization after treatment with CaTx-II versus 2% Fusidic Acid ointment (FAO) treated controls. Measurement of tissue cytokines revealed that interleukin-1 beta (IL-1β) expression in CaTx-II treated mice was significantly suppressed versus untreated controls. In contrast, cytokines involved in wound healing and cell migration i.e., monocyte chemotactic protein-1 (MCP-1), fibroblast growth factor-basic (FGF-b), chemokine (KC), granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly enhanced in CaTx-II treated mice, but not in the controls. CaTx-II also modulated nuclear factor-kappa B (NF-κB) activation during skin wound healing. The CaTx-II protein highlights distinct snake proteins as a potential source of novel antimicrobial agents with significant therapeutic application for bacterial skin infections.
[Show abstract][Hide abstract] ABSTRACT: Clostridium perfringens is a prolific, toxin-producing anaerobe causing multiple diseases in humans and animals. One of these toxins is epsilon, a 33 kDa protein produced by Clostridium perfringens (types B and D) that induces fatal enteric disease of goats, sheep and cattle. Epsilon toxin (Etx) belongs to the aerolysin-like toxin family. It contains three distinct domains, is proteolytically-activated and forms oligomeric pores on cell surfaces via a lipid raft-associated protein(s). Vaccination controls Etx-induced disease in the field. However, therapeutic measures are currently lacking. This review initially introduces C. perfringens toxins, subsequently focusing upon the Etx and its biochemistry, disease characteristics in various animals that include laboratory models (in vitro and in vivo), and finally control mechanisms (vaccines and therapeutics).
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial and anti-inflammatory activities of hydrocarbon esters obtained from Tragia involucrata were evaluated by disk-diffusion (250 μg/ml), and broth-dilution (500-7.8 μg/ml), methods against bacteria. Among the compounds, shellsol showed the most potent activity against Burkholderia pseudomallei (KHW), Aeromonas hydrophila, Staphylococcus aureus, Bacillus subtilis, Streptococcus pyogenes, Klebsiella pneumoniae, Proteus mirabilis, and Streptococcus pneumoniae. Interestingly, vinyl hexylether was active against food-spoilage bacteria (Bacillus cereus and Proteus vulgaris), 2, 4-methyl hexane also exerted antimicrobial activity against K. pneumoniae, S. pyogenes, B. pseudomallei, Alcaligens viscolactis, and Pseudomonas aeruginosa. 2-methylnonane and 2, 6-dimethyl heptane showed only weak activity. For example, shellsol showed bacteriostatic effect (MIC of 7.8 μg/ml) against A. hydrophila, vinyl hexylether (MIC of 15.6 μg/ml) against P. mirabilis, and 2, 4-methyl hexane (MIC of 31.25 μg/ml) on B. pseudomallei. Cytotoxic effects of compounds were assayed in human skin and monkey kidney cells (62.5-2000 g/ml) by an XTT assay. The vinyl hexylether, 2, 4-dimethyl hexane and shellsol did not show any toxicity up to 1000 μg/ml concentrations. The 2-methylnonane and 2, 6-dimethyl heptane induced morphological changes (e.g. cell disintegration and lysis) of both cell types at a 2000 μg/ml. The vinyl hexylether, 2, 4-dimethyl hexane and shellsol were devoid of toxic effects; however, 2-methylnonane induced weight loss and severe necrosis as evidenced by histopathological and serum biochemical analysis in rats. Interestingly, shellsol showed the maximum inhibition of carrageenan-induced, paw oedema in rats. In conclusion, findings of this study clearly indicate that biologically active hydrocarbon esters, such as shellsol, vinyl hexylether, and 2, 4-dimethyl hexane isolated from T. involucrata, may effectively control the growth of certain food-borne and food-spoilage pathogens.
[Show abstract][Hide abstract] ABSTRACT: Animals produce a large variety of antimicrobial peptides that play an important role in natural innate immunity and controlling microbial infections. Snakes are classified into the phylum Chordata and class Reptilia, within the animal kingdom. Snake venoms are extensive mixtures that contain a large number of biologically active proteins/peptides that represent a promising source of potential therapeutics for both humans and animals. These components are extensively studied for a wide range of pharmacological properties; however, it is quite exceptional that very little is relatively known about antimicrobial activity associated with venoms to date. In this review, we emphasize the available literature linked to antimicrobial activity of venom proteins such as L-amino acid oxidase (LAAO), phospholipase A2 (PLA2), peptides and snake cathelicidin. We propose a model for antimicrobial action in comparison with existing mechanisms. Structure and function of snake venom proteins/peptides in relation to antimicrobial activity and its involvement in molecular pharmacology thoroughly discussed. Nevertheless, snake venom enzymes and various classes of peptides have unique pharmacological properties, enhanced properties of antimicrobial effects against various bacterial infections, as well as varying levels of toxicity on eukaryotic and prokaryotic cells. In conclusions, these peptide-based molecules may ultimately be used as alternative drugs to replace chemical antibiotics that increasingly become less useful due to highly-evolved resistance mechanisms employed by various microbial pathogens.
No preview · Article · Jun 2013 · Current Proteomics
[Show abstract][Hide abstract] ABSTRACT: Staphylococcus aureus plays an important role in numerous human cases of food poisoning, soft tissue and bone infections, as well as potentially lethal toxic shock. This common bacterium synthesizes various virulence factors that include staphylococcal enterotoxins (SEs). These protein toxins bind directly to major histocompatibility complex class II on antigen-presenting cells and specific Vβ regions of T-cell receptors, resulting in potentially life-threatening stimulation of the immune system. Picomolar concentrations of SEs ultimately elicit proinflammatory cytokines that can induce fever, hypotension, multi-organ failure, and lethal shock. Various in vitro and in vivo models have provided important tools for studying the biological effects of, as well as potential vaccines/therapeutics against, the SEs. This review succinctly presents known physical and biological properties of the SEs, including various intervention strategies. In particular, SEB will often be portrayed as per biodefense concerns dating back to the 1960s.
[Show abstract][Hide abstract] ABSTRACT: Snake venom contains a number of different, pharmacologically-active proteins and peptides. Most of the haemorrhagic proteins of snake venoms are metalloproteinases. Agkistrodon halys metalloproteinase (AHM) was isolated from the snake venom of Pallas (Mol wt. 23145). In vitro toxicological effects of AHM (0.1-2 mM) on human macrophages (THP-1 and U-937), lung fibroblasts (MRC-5) and murine lung epithelial (LA4) cells were evaluated by (2,3-bis- (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-hydroxide) assay and light microscopy. AHM strongly inhibited cell proliferation and adhesion to extracellular matrix, as well as induced morphological changes in a dose-dependent manner. Apoptosis was evaluated using propidium iodide (PI) staining and a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay for DNA fragmentation. PI staining indicated an accumulation of cells at the sub-G1-phase following AHM treatment, and there was also DNA fragmentation as shown by TUNEL staining. Besides cell-based assays, an in vivo assessment of AHM (1.56-300 mg/kg, body weight) in mice was also done. Histopathology of muscle fibers revealed massive necrotic aggregations after AHM exposure. There were translucent vacuoles in the purkinje cells, which may cause substantial damage to kidney tubular epithelium. There were also clear areas in the cerebellum due to cell death, deposition of fibrinogen or fibrin on the intestinal epithelium, and skin necrosis following an AHM dose of 300 mg/kg. We also observed marked erythrocyte accumulation in lung alveolar walls that resulted in infarction, along with a consequent reduction of the alveolar space and necrosis linked to neutrophil infiltration. These results cumulatively suggest that AHM induces lethality at high doses, inhibits cell proliferation, and induces morphological changes in various cell types.
No preview · Article · Jan 2013 · Current Chemical Biology
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is the most common cancer among women. To date, improvements in hormonal and cytotoxic therapies have not yet led to a sustained remission or cure. In the present study, we investigated the in vitro and in vivo antitumor activities of a novel Calotropis procera protein (CP-P) isolated from root bark. CP-P protein inhibited the proliferation and induced apoptosis of breast cancer cells through the suppression of nuclear factor kappaB (NF-kB) activation. CP-P, when administered individually or in combination with cyclophosphamide (CYC, 0.2 mg/kg) to rats with 7, 12-dimethyl benz(a)anthracene (DMBA)-induced breast cancer decreased tumor volume significantly without affecting the body weight. To elucidate the anticancer mechanism of CP-P, antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and non-enzymatic antioxidant - reduced glutathione (GSH), vitamin E and C generation in the breast were analyzed by various assays. SOD, CAT, GST, GSH, vitamin E and C levels were high in combination-treated groups (CP-P+CYC) versus the CYC alone-treated groups. Also, the combination was more effective in down-regulating the expression of NF-kB-regulated gene products (cyclin D1 and Bcl-2) in breast tumor tissues. Our findings indicate that CP-P possesses significant antitumor activity comparable to a commonly used anticancer drug, cyclophosphamide, and may form the basis of a novel therapy for breast cancer.
[Show abstract][Hide abstract] ABSTRACT: Various pathogenic clostridia produce binary protein toxins associated with enteric diseases of humans and animals. Separate binding/translocation (B) components bind to a protein receptor on the cell surface, assemble with enzymatic (A) component(s), and mediate endocytosis of the toxin complex. Ultimately there is translocation of A component(s) from acidified endosomes into the cytosol, leading to destruction of the actin cytoskeleton. Our results revealed that CD44, a multifunctional surface protein of mammalian cells, facilitates intoxication by the iota family of clostridial binary toxins. Specific antibody against CD44 inhibited cytotoxicity of the prototypical Clostridium perfringens iota toxin. Versus CD44(+) melanoma cells, those lacking CD44 bound less toxin and were dose-dependently resistant to C. perfringens iota, as well as Clostridium difficile and Clostridium spiroforme iota-like, toxins. Purified CD44 specifically interacted in vitro with iota and iota-like, but not related Clostridium botulinum C2, toxins. Furthermore, CD44 knockout mice were resistant to iota toxin lethality. Collective data reveal an important role for CD44 during intoxication by a family of clostridial binary toxins.
[Show abstract][Hide abstract] ABSTRACT: The majority of snake venom phospholipases A2 (svPLA2s) are toxic and induce a wide spectrum of biological effects. They are cysteine-rich proteins that contain 119-134 amino acids and share similar structures and functions. About 50% of the residues are incorporated into α-helices, whereas only 10% are in β -sheets. Fourteen conserved cysteines form a network of seven disulfide bridges that stabilize the tertiary structure. They show a high degree of sequence and structural similarity, and are believed to have a common calcium-dependent catalytic mechanism. Additionally, svPLA2s display an array of biological actions that are either dependent or independent of catalysis. The PLA2s of mammalian origin also exert potent bactericidal activity by binding to anionic surfaces and enzymatic degradation of phospholipids in the target membranes, preferentially of Gram-positive species. The bactericidal activity against Gram-negatives by svPLA2 requires a synergistic action with bactericidal/permeability-increasing protein (BPI), but is equally dependent on enzymatic-based membrane degradation. Several hypotheses account for the bactericidal properties of svPLA2s, which include fatal depolarization of the bacterial membrane, creation of physical holes in the membrane, scrambling of normal distribution of lipids between the bilayer leaflets, and damage of critical intracellular targets after internalization of the peptide. The present review discusses several svPLA2s and derived peptides that exhibit strong bactericidal activity. The reports demonstrate that svPLA2 -derived peptides have the potential to counteract microbial infections. In fact, the C-terminal cationic/hydrophobic segment (residues 115-129) of svPLA2s is bactericidal. Thus identification of the bactericidal sites in svPLA2s has potential for developing novel antimicrobials.
No preview · Article · Sep 2012 · Current Medicinal Chemistry
[Show abstract][Hide abstract] ABSTRACT: Mycoplasma genitalium is a globally important sexually transmitted pathogen. Men infected with M. genitalium frequently present with dysuria, while women may present with or without urogenital symptoms. In some populations, M. genitalium is significantly associated with HIV-1 infection, and is also an etiological agent in pelvic inflammatory disease. However, there is insufficient evidence to establish a causative role of the organism in obstetric complications, including tubal factor infertility. Although several nucleic acid amplification tests offer rapid, sensitive methods for detecting M. genitalium, there is no standardized assay. Available evidence supports treatment of M. genitalium infections with an extended regimen of azithromycin and resistant strains respond to moxifloxacin. Accumulating evidence indicates growing fluoroquinolone resistance, including against moxifloxacin, emphasizing the need for new therapeutic strategies to treat M. genitalium infections.
[Show abstract][Hide abstract] ABSTRACT: There are many pathogenic Clostridium species with diverse virulence factors that include protein toxins. Some of these bacteria, such as C. botulinum, C. difficile, C. perfringens, and C. spiroforme, cause enteric problems in animals as well as humans. These often fatal diseases can partly be attributed to binary protein toxins that follow a classic AB paradigm. Within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-ADP-ribosylation of globular actin by the A component. However, much less is known about B component binding to cell-surface receptors. These toxins share sequence homology amongst themselves and with those produced by another Gram-positive, spore-forming bacterium also commonly associated with soil and disease: Bacillus anthracis. This review focuses upon the iota and C2 families of clostridial binary toxins and includes: (1) basics of the bacterial source; (2) toxin biochemistry; (3) sophisticated cellular uptake machinery; and (4) host-cell responses following toxin-mediated disruption of the cytoskeleton. In summary, these protein toxins aid diverse enteric species within the genus Clostridium.
Preview · Article · Dec 2011 · Frontiers in Cellular and Infection Microbiology
[Show abstract][Hide abstract] ABSTRACT: Potential bioweapons are biological agents (bacteria, viruses, and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons, or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus, and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases.