Antibiotic-resistant Superbugs Research Articles

Soft nanotechnology: Used as a functional coating on a nanostructured germicidal surface

Bacterial contamination has emerged as a significant threat to human health over the past century. Initially, antibiotics were seen as the solution to this problem, but their overuse has led to the development of drug resistance and the rise of superbugs. These superbugs are resistant to most, if not all, conventional antibiotics, making them particularly difficult to treat. Interestingly, research has shown that the wings of dragonflies and cicadas possess natural nanopillar structures that are capable of inhibiting bacterial growth. These nanopillars puncture bacterial cell membranes, leading to bacterial death. This discovery has opened up new avenues for combating bacterial contamination. Recent advancements in soft nanotechnology have introduced innovative antibacterial coatings that are crucial for combating these antibiotic-resistant superbugs. These coatings work by mimicking the nanopillar structures found on the wings of dragonflies and cicadas. Understanding the interaction between bacteria and these nanoantibacterial coatings is essential for achieving effective bactericidal outcomes. Different bacteria require varying optimum aspect ratios, which can be achieved through various formation methods. Therefore, this paper elucidates the principles of soft nanocoating, with a focus on comparing aspect ratios obtained through different preparation techniques and, according to the different aspect ratio, determining the corresponding applicable sterilization scene. It also explores the practical application of nanostructure bactericidal surface coatings to address the growing threat of antibiotic resistance and enhance public health. Moreover, as an emerging field, this paper examines the challenges in soft nanocoating applications and the directions that can be improved in the future. The versatility and potential of soft nanotechnological coatings seems to apply to various industries, promising enhanced performance and safety standards. This is a crucial step towards creating a safer and healthier future for all.

A newly isolated strain of Bacillus subtilis W2Z exhibited probiotic effects on juvenile red claw crayfish, Cherax quadricarinatus

Aquaculture traditionally used antibiotics, leading to environmental contamination, food residue, and antibiotic-resistant superbugs. Probiotics offer a promising antibiotic alternative. In this study, a strain of Bacillus subtilis W2Z was isolated from aquaculture environments and can inhibit pathogens in aquaculture food production through chemical compounds. Eight-weeks C. quadricarinatus cultivation experiments revealed that B. subtilis W2Z, as a probiotic, contributes to increasing the yield of red claw crayfish. The supplementation of strain W2Z in the feed enhanced the crayfish's resistance to Aeromonas hydrophila by increasing immune-related enzyme activity and improving intestinal microbiota. B. subtilis W2Z has significant potential as a bioresource for exploring probiotics in crustacean aquaculture. Adding B. subtilis W2Z to C. quadricarinatus feed at a concentration of 1 × 108 to 1 × 109 colony forming unit (CFU)/g is recommended.

Bio-manufacturing: The future of food production

Bio-manufacturing: The future of food production The future of food production is bio-manufacturing. Here, we discover Multus is helping it scale. Without humans, just 3% of land-based mammals are wild animals by weight. Global meat production eclipsed 347,000,000,000 kg in 2022 (OECD/FAO, 2023), contributing to more greenhouse gas emissions than cars, trucks, ships and planes combined and using 73% of global antibiotics (K. Tiseo et al., 2020). By 2050, the World Health Organization estimates up to 10 million deaths – the same as cancer – could be caused by antibiotic-resistant superbugs. Our consumption of meat from intensive farming is literally consuming the planet. Yet, global demand for meat continues to rise. Over the next ten years, meat demand is set to increase by an additional 41,000,000,000 kg per year (OECD/FAO, 2023).

Superbugs: An invicible threat in post antibiotic era

BackgroundSuperbug resistance is a very rare, invincible global problem arising as a threat in hospitals as well as in the community. Methicillin-Resistant Staphylococcus aureus(MRSA), Vancomycin-Resistant Enterococci (VRE) and Multidrug-resistant Gram-negative bacilli (MDR-GNB) etc are the most deadly contagious strains. This study discloses the prevalence and risk factors associated with superbugs there by aiding the adoption of preventive measures to reduce resistance patterns in hospital settings. AimIdentification of the superbug that predominantly shows antibiotic resistance in hospitals and analyzing the risk factors for the occurrence of antibiotic resistance. Materials and methodsA prospective observational study was conducted for one year, from 1st September 2019 to 31st July 2020 to evaluate the prevalence and risk factors of antibiotic-resistant superbugs among the 80 patients selected from the various departments (General Medicine, General Surgery, Nephrology, Pulmonology,Orthopedics, orthopaedicsurgery,Neurology, Urology,and Neurosurgery) of a tertiary care referral hospital. ResultsMethicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were antibiotic-resistant superbugs that predominantly showed resistance in hospital settings. ConclusionPseudomonas aeruginosa and Methicillin-resistant superbugs were the predominantly found superbugs in hospital settings. Major risk factors for antibiotic-resistant superbugs were found to be Prolonged hospitalization, previous antibiotic therapy, failure to take the antibiotic as prescribed by physicians, patient co-morbid conditions, prophylactic use of antibiotics, patient diet etc.

Impact of environment on transmission of antibiotic-resistant superbugs in humans and strategies to lower dissemination of antibiotic resistance.

Antibiotics are the most efficient type of therapy developed in the twentieth century. From the early 1960s to the present, the rate of discovery of new and therapeutically useful classes of antibiotics has significantly decreased. As a result of antibiotic use, novel strains emerge that limit the efficiency of therapies in patients, resulting in serious consequences such as morbidity or mortality, as well as clinical difficulties. Antibiotic resistance has created major concern and has a greater impact on global health. Horizontal and vertical gene transfers are two mechanisms involved in the spread of antibiotic resistance genes (ARGs) through environmental sources such as wastewater treatment plants, agriculture, soil, manure, and hospital-associated area discharges. Mobile genetic elements have an important part in microbe selection pressure and in spreading their genes into new microbial communities; additionally, it establishes a loop between the environment, animals, and humans. This review contains antibiotics and their resistance mechanisms, diffusion of ARGs, prevention of ARG transmission, tactics involved in microbiome identification, and therapies that aid to minimize infection, which are explored further below. The emergence of ARGs and antibiotic-resistant bacteria (ARB) is an unavoidable threat to global health. The discovery of novel antimicrobial agents derived from natural products shifts the focus from chemical modification of existing antibiotic chemical composition. In the future, metagenomic research could aid in the identification of antimicrobial resistance genes in the environment. Novel therapeutics may reduce infection and the transmission of ARGs.

Eradication of bacterial persister cells by leveraging their low metabolic activity using adenosine triphosphate coated gold nanoclusters

Bacteria first develop tolerance after antibiotic exposure; later genetic resistance emerges through the population of tolerant bacteria. Bacterial persister cells are the multidrug-tolerant subpopulation within an isogenic bacteria culture that maintains genetic susceptibility to antibiotics. Because of this link between antibiotic tolerance and resistance and the rise of antibiotic resistance, there is a pressing need to develop treatments to eradicate persister cells. Current anti persister cell strategies are based on the paradigm of "awakening" them from their low metabolic state before attempting eradication with traditional antibiotics. Herein, we demonstrate that the low metabolic activity of persister cells can be exploited for eradication over their metabolically active counterparts. We engineered gold nanoclusters coated with adenosine triphosphate (AuNC@ATP) as a benchmark nanocluster that kills persister cells over exponential growth bacterial cells and prove the feasibility of this new concept. Finally, using AuNC@ATP as a new research tool, we demonstrated that it is possible to prevent the emergence of antibiotic-resistant superbugs with an anti-persister compound. Eradicating persister cells with AuNC@ATP in an isogenic culture of bacteria stops the emergence of superbug bacteria mediated by the sub-lethal dose of conventional antibiotics. Our findings lay the groundwork for developing novel nano-antibiotics targeting persister cells, which promise to prevent the emergence of superbugs and prolong the lifespan of currently available antibiotics.

Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency.

The rise in nosocomial infections caused by multidrug-resistant pathogens is a major public health concern. Patients taking immunosuppressants or chemotherapeutics are naturally more susceptible to infections. Thus, strategies for protecting immunodeficient individuals from infections are of great importance. Here, we investigate the effectiveness of a biomimetic nanotoxoid vaccine in defending animals with immunodeficiency against Pseudomonas aeruginosa. The nanotoxoids use a macrophage membrane coating to sequester and safely present bacterial virulence factors that would otherwise be too toxic to administer. Vaccination with the nanoformulation results in rapid and long-lasting immunity, protecting against lethal infections despite severe immunodeficiency. The nanovaccine can be administered through multiple routes and is effective in both pneumonia and septicemia models of infection. Mechanistically, protection is mediated by neutrophils and pathogen-specific antibodies. Overall, nanotoxoid vaccination is an attractive strategy to protect vulnerable patients and could help to mitigate the threat posed by antibiotic-resistant superbugs.

Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection

SummaryNovel treatment strategies are in urgent need to deal with the rapid development of antibiotic-resistant superbugs. Combination therapies and targeted drug delivery have been exploited to promote treatment efficacies. In this study, we loaded neutrophils with azithromycin and colistin to combine the advantages of antibiotic combinations, targeted delivery, and immunomodulatory effect of azithromycin to treat infections caused by Gram-negative pathogens. Delivery of colistin into neutrophils was mediated by fusogenic liposome, while azithromycin was directly taken up by neutrophils. Neutrophils loaded with the drugs maintained the abilitity to generate reactive oxygen species and migrate. In vitro assays demonstrated enhanced bactericidal activity against multidrug-resistant pathogens and reduced inflammatory cytokine production by the drug-loaded neutrophils. A single intravenous administration of the drug-loaded neutrophils effectively protected mice from Pseudomonas aeruginosa infection in an acute pneumonia model. This study provides a potential effective therapeutic approach for the treatment of bacterial infections.

Anti-bacterial monoclonal antibodies: next generation therapy against superbugs.

Prior to the nineteenth century, infectious disease was one of the leading causes of death. Human life expectancy has roughly doubled over the past century as a result of the development of antibiotics and vaccines. However, the emergence of antibiotic-resistant superbugs brings new challenges. The side effects of broad-spectrum antibiotics, such as causing antimicrobial resistance and destroying the normal flora, often limit their applications. Furthermore, the development of new antibiotics has lagged far behind the emergence and spread of antibiotic resistance. On the other hand, the genome complexity of bacteria makes it difficult to create effective vaccines. Therefore, novel therapeutic agents in supplement to antibiotics and vaccines are urgently needed to improve the treatment of infections. In recent years, monoclonal antibodies (mAbs) have achieved remarkable clinical success in a variety of fields. In the treatment of infectious diseases, mAbs can play functions through multiple mechanisms, including toxins neutralization, virulence factors inhibition, complement-mediated killing activity, and opsonic phagocytosis. Toxins and bacterial surface components are good targets to generate antibodies against. The U.S. FDA has approved three monoclonal antibody drugs, and there are numerous candidates in the preclinical or clinical trial stages. This article reviews recent advances in the research and development of anti-bacterial monoclonal antibody drugs in order to provide a valuable reference for future studies in this area. KEY POINTS: • Novel drugs against antibiotic-resistant superbugs are urgently required • Monoclonal antibodies can treat bacterial infections through multiple mechanisms • There are many anti-bacterial monoclonal antibodies developed in recent years and some candidates have entered the preclinical or clinical stages of development.

A Microbe-Derived Efflux Pump Inhibitor of the Resistance-Nodulation-Cell Division Protein Restores Antibiotic Susceptibility in Escherichia coli and Pseudomonas aeruginosa

The use of efflux pump inhibitors (EPIs) as potentiators along with the traditional antibiotics assists in the warfare against antibiotic-resistant superbugs. Efflux pumps of the resistance-nodulation-cell division (RND) family play crucial roles in multidrug resistance in Escherichia coli and Pseudomonas aeruginosa. Despite several efforts, clinically useful inhibitors are not available at present. This study describes ethyl 4-bromopyrrole-2-carboxylate (RP1) isolation, an inhibitor of RND transporters from the library of 4000 microbial exudates. RP1 acts synergistically with antibiotics by reducing their minimum inhibitory concentration in strains overexpressing archetype RND transporters (AcrAB-TolC and MexAB-OprM). It also improves the accumulation of Hoechst 33342 and inhibits its efflux (a hallmark of EPI functionality). The antibiotic-RP1 combinations prolong the postantibiotic effects and reduce the mutation prevention concentration of antibiotics. Additionally, from Biolayer Interferometry spectra, it appears that RP1 is bound to AcrB. RP1 displays low mammalian cytotoxicity, no Ca2+ channel inhibitory effects, and reduces the intracellular invasion of E.coli and P.aeruginosa in macrophages. Furthermore, the RP1-levofloxacin combination is nontoxic, well-tolerated, and notably effective in a murine lung infection model. In sum, RP1 is a potent EPI and worthy of further consideration as a potentiator to improve the effectiveness of existing antibiotics.

Platinum ions mediate the interactions between DNA and carbon quantum dots: diagnosis of MRSA infections.

In this study, we have developed a rapid and cost-effective method employing platinum ion (Pt4+)-capped fluorescent carbon quantum dots (CQDs) coupled with loop-mediated isothermal amplification (LAMP) to detect dual MRSA genes. We synthesized nitrogen- and chlorine-co-doped fluorescent CQDs (CQDSPDs) from spermidine trihydrochloride via a simple one-step pyrolysis. The CQDSPDs capped with Pt4+ ions through the cooperative coordination of the amine and chlorine groups on the surface of CQDs facilitated the double-stranded DNA (dsDNA)-induced fluorescence quenching of CQDs, and enabled the construction of the CQDSPDs/Pt4+ probe for the detection of as few as 10 copies of the MRSA gene (mecA and femA). The sensitivity and specificity of the CQDSPDs/Pt4+ probe for MRSA detection in clinical specimens (n = 24) were 94% and 86%, respectively. Our results reveal that the CQDSPDs/Pt4+ probe has great potential for the diagnosis of antibiotic-resistant superbugs with high sensitivity, specificity, and agreement.

Pro-caspase-3 protects cells from polymyxin B-induced cytotoxicity by preventing ROS accumulation

Polymyxin B (PMB), a last-line antibiotic used against antibiotic-resistant superbugs, causes undesirable cytotoxic side effects. However, its mechanisms remain unknown. In this study, we unexpectedly found that caspase-3, a main executor of apoptosis, plays a protective role in PMB-induced cytotoxicity. Caspase-3 knockout (KO) cells exhibited higher susceptibility to PMB-induced cytotoxicity compared with wild-type (WT) cells, accompanied by increased levels of reactive oxygen species (ROS). Interestingly, co-treatment with the antioxidant N-acetylcysteine (NAC) rescued cell viability to a similar extent as WT cells. Furthermore, PMB failed to facilitate the processing of inactive caspase-3 (pro-caspase-3) into active forms, suggesting that pro-caspase-3 nonenzymatically suppresses PMB-driven ROS accumulation and its cytotoxicity. Thus, our findings that demonstrate the potential ability of PMB to stimulate ROS generation, but which is normally masked by pro-caspase-3-dependent mechanisms, may provide novel insights into the mechanisms of PMB-induced side effects.

NIR-Light-Active ZnO-Based Nanohybrids for Bacterial Biofilm Treatment.

Nanomaterials with antimicrobial properties triggered by external stimuli appear to be a promising and innovative substitute for the destruction of antibiotic-resistant superbugs as they can induce multiple disruptions in the cellular mechanism. This study demonstrates the use of squaraine (SQ) dye as the photosensitive material, activated in the near-infrared tissue-transparent therapeutic window. The dye has been covalently attached to the ZnO nanoparticle surface, forming ZnO-SQ nanohybrids. The formation of the nanohybrids is confirmed using Fourier transform infrared and other optical spectroscopic methods. The photoinduced interfacial electron transfer process (as confirmed using the time-resolved fluorescence technique) from the excited state of SQ to the conduction band of ZnO is responsible for the greater reactive oxygen species (ROS) generation ability of the nanohybrid. The production of photoactivated ROS (especially singlet oxygen species) by ZnO-SQ provides remarkable antimicrobial action against clinically significant Staphylococcus aureus. Detailed investigations suggest synergistic involvement of cell membrane disruption and nanoparticle internalization followed by photoinduced intracellular ROS generation, which result in an unprecedented 95% bacterial killing activity by the nanohybrid. Moreover, the efficacy of the nanohybrid for disruption of bacterial biofilms has been examined. The electron microscopic images suggest significant bacterial cell death following structural alteration and reduced adherence property of the biofilms. Nanodimension-driven greater internalization of ZnO-SQ followed by an improved dissolution of ZnO in an acidic environment of the biofilm as well as red-light-driven interfacial charge separation and ROS generation improves the efficacy of the material for biofilm destruction. An artificial medical implant mimicking titanium sheets coated with ZnO-SQ depicts light-triggered disruption in the adherence property of matured biofilms. The cytotoxicity and hemolysis assays show inherent biocompatibility of the photoactive nanohybrid. This study is notably promising for the treatment of life-threatening drug-resistant infections and eradication of biofilms formed within artificial implants.

Emergence and characterization of nosocomial multidrug-resistant and extensively drug-resistant Acinetobacter baumannii isolates in Tehran, Iran.

Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings. The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A.baumannii as a result of dissemination of resistant strains. Clinical and environmental isolates of A.baumannii were obtained from patients, staff, and environment of an educational hospital in Tehran. Antimicrobial susceptibility testing was carried out using the disk diffusion and E-test methods. Multiplex PCR was performed for detection of OXA-type genes (blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, and blaOXA-51-like). Genotypic relatedness of the isolates was achieved using repetitive extragenic palindromic element PCR (Rep-PCR) technique. All the isolates were found to be susceptible to colistin and most of them (77%) were non-susceptible to tigecycline. A majority of the clinical and environmental isolates (97%) were considered as MDR strains and 41% as XDR. In multiplex detection, blaOXA-23-like was found in 54% of the isolates, which was the most frequent OXA-type gene. In addition, the frequency of the carbapenem-resistant A.baumannii (CRAB) was observed to be high (96%). In addition, molecular typing showed different Rep patterns of clinical isolates and clonal spread of environmental isolates. The present study highlights the circulation of drug-resistant A.baumannii strains in different wards of hospitals principally in intensive care unit (ICU) as a nosocomial pathogen due to unwise managements.

Corrosion and Critical Solute Content of Corrosion-Resistant Binary Solid Solution Cu-Al Alloys in Artificial Perspiration Solution: Implications Towards Tunable Cu-Based Alloys for Antimicrobial Surfaces

Copper and its alloys as high-touch surfaces can be antimicrobial, capable of killing even antibiotic-resistant superbugs including Methicillin-resistant Staphylococcus aureus (MRSA)1–5 through controlled release of Cu(I)/Cu(II) cations as a result of corrosion. Therefore, there is interest in designing tunable Cu alloys with regulated dissolution and passivation properties. The inability to predict electrochemical behavior as a function of alloying content remains a critical challenge in both corrosion and electrochemical materials science. Yet, a lack of scientific understanding persists concerning how alloying controls soluble Cu cation release (antimicrobial function) of Cu-based alloys.6–10 A tunable alloy system is needed to balance antimicrobial efficacy, i.e. soluble Cu cation release, with tarnish-resistance which can both be regulated using alloy content optimization. Aluminum bronzes are of interest to study in this context for their relatively improved corrosion resistance due in part to formation of a tarnish-resistant oxide film.11–14The focus of this work is to investigate critical governing mechanisms associated with alloyed Al on protective oxide layer formation in FCC α-Cu, as a function of Al content. This investigation specifically addresses behavior in a realistic environment for high-touch surfaces where these pathogenic bacteria proliferate: human perspiration. To quantitatively interrogate the effect of alloying FCC α-Cu with Al on corrosion and cation release, commercially pure Cu (Cu), and high-purity arc-melted solid solution alloys consisting of Cu-0.1Al, Cu-1Al and Cu-5Al (wt%) were evaluated in modified artificial human perspiration solution.15 Open circuit corrosion exposures were conducted for up to 130 hours to determine corrosion rate and the fate of Cu and Al. Released aqueous ion concentrations were monitored via inductively-coupled plasma – optical emission spectroscopy (ICP-OES). Al was not observed as a soluble ionic species within ICP-OES limits of detection (LOD). Corrosion products were characterized using grazing incidence X-ray diffraction (GIXRD), Raman spectroscopy, and quantified with coulometric reduction (CR). Corrosion rates were assessed with mass loss and electrochemical impedance spectroscopy (EIS). Quantitative results of total anodic charge, from both mass loss and calculated from EIS-determined corrosion rates were converted to charge and directly compared to corrosion product charge (CR) and dissolution charge (ICP-OES) to determine the fate of the elements: Cu and Al, through charge balance as a function of Al alloying content. Diagnostic chemical environments were employed where only selected corrosion products are stable e.g., Al2O3 in citric/citrate buffer. For instance, HCl and deaerated citric/citrate buffer solution (CBS) were employed to determine the individual roles of Al in the metal as a metal solute and as an oxidized surface film, respectively. Primary corrosion products were revealed to be Cu2O and an inner layer of Al2O3 for Al-containing alloys. Cu was dissolved as cuprous (Cu+) ions. Minor Al alloying in solid solution catalyzed Cu dissolution which was counteracted at higher Al contents by a partially passivating layer of Al2O3, achieving complete passivity at ~6 wt% Al according to graph theory.16,17 In contrast, Cu-Al alloys corroded more readily with increasing Al content in the absence of a protective oxide film. The effect of alloyed Al as a dissolution promoter for electrochemical Cu ion release, critical Al contents for stable passivity, and subsequent implications for functional antimicrobial alloys are discussed. These results point to the possibility of making tunable Cu-based alloys for antimicrobial function.

Titanium surfaces immobilized with the major antimicrobial fragment FK-16 of human cathelicidin LL-37 are potent against multiple antibiotic-resistant bacteria

Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors’ laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17–32) of LL-37. FK-16 is superior to the longer peptide LL-37 in terms of synthesis cost and the shorter peptide KR-12 in terms of activity spectrum. Indeed, the FK16-coated titanium surface showed a broad-spectrum activity against the ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It also demonstrated anti-adhesion and biofilm inhibition capabilities against both S. aureus and E. coli.

Tiny Answers to Big Questions

Tiny Answers to Big Questions

Antibiotic Resistant Superbugs: Assessment of the Interrelationship of Occurrence in Clinical Settings and Environmental Niches.

The increasing threat to global health posed by antibiotic resistance remains of serious concern. Human health remains at higher risk due to several reported therapeutic failures to many life threatening drug resistant microbial infections. The resultant effects have been prolonged hospital stay, higher cost of alternative therapy, increased mortality, etc. This opinionated review considers the two main concerns in integrated human health risk assessment (i.e., residual antibiotics and antibiotic resistant genes) in various compartments of human environment, as well as clinical dynamics associated with the development and transfer of antibiotic resistance (AR). Contributions of quorum sensing, biofilms, enzyme production, and small colony variants in bacteria, among other factors in soil, water, animal farm and clinical settings were also considered. Every potential factor in environmental and clinical settings that brings about AR needs to be identified for the summative effects in overall resistance. There is a need to embrace coordinated multi-locational approaches and interrelationships to track the emergence of resistance in different niches in soil and water versus the hospital environment. The further integration with advocacy, legislation, enforcement, technological innovations and further research input and recourse to WHO guidelines on antibiotic policy would be advantageous towards addressing the emergence of antibiotic resistant superbugs.

ICU nurses' scrubs 'harbour superbugs'.

Scrubs worn by intensive care nurses can harbour antibiotic-resistant superbugs, according to a US study.

HDFx: A Recently Discovered Biologic and its Potential Use in Prevention and Treatment of Hemorrhagic Fever Viruses and Antibiotic-Resistant Superbugs

Recently, we have reported on the discovery of a new, conserved protein (35-40 kDa) that protects rats, mice, guinea-pigs, and rabbits against lethal hemorrhage, endotoxins, live lethal bacterial and fungal microorganisms, and traumatic injuries when given prophylactally and therapeutically. HDFx was found to stimulate several arms of the innate immune system (e.g. macrophages, NK cells). HDFx was also found to stabilize the microcirculation, prevent rupture and leakage of postcapillary venules, prevent adhesion of platelets to endothelium and loss of platelets, stabilize falls in arterial blood pressure, and prevent stasis and pooling of blood in the postcapillary vessels, as observed by intra-vital high-resolution TV microscopy. HDFx also stimulates phagocytic uptake of foreign particulate matter and bacteria by liver Kupffer cells, splenic macrophages, and circulating macrophages. It also prevents explosive release of cytokines and chemokines from macrophages and lymphocytes in animals subjected to live bacteria, endotoxins, trauma and combined injuries. Surprisingly, HDFx was found to accelerate wound healing and aid the regeneration of tissues. Repeated administration of HDFx, over many months, does not result in either diminished protective activity or detectable organ or tissue pathologies. One of the major consequences of infections and wars/conflicts is loss of the ability to regenerate normal physiologic functions of numerous organs and tissues. A major characteristic of invasion of the body by septic-endotoxic microorganisms and hemorrhagic fever viruses (HFVs) is that these entities eventuate in rupture of the microvessels in the capillary circulation of numerous organs and tissues leading to massive blood and fluid loss, making the body susceptible to superimposed infections and loss of immuno-competence. About 100 million people are infected worldwide, annually, with about 60,000 to 75,000 deaths per year from HFVs. Added to these numbers are the numerous hospital-borne and food-borne infections along with infections resulting from major disasters (hurricanes, tornados, earthquakes, etc.) that cause 75,000 to 100,000 deaths per year in the U.S.A. alone. The ability and uniqueness of HDFx to minimize infections, accelerate wound healing, and promote tissue regeneration should greatly aid treatment and recovery of these victims and be of great value in infections from HFVs and on battlefields.