Treatment Of Bacterial Infectious Diseases Research Articles

A Chemo/photo-responsive immunomodulatory nanoplatform for treatment of multidrug-resistant bacterial sepsis

Multidrug resistant (MDR) bacterial infection has significantly disturbed human health, which may be even fatal in clinical practice. To deal with severe infection induced by MDR bacteria, we have proposed a multifunctional platform on basis of ultrasmall polyethyleneimine (PEI) etched SiC nanodots co-loading with L-arginine (L-Arg) and indocyanine green (ICG). The as-fabricated SiC@PEI-L-Arg/ICG (SPAI) can thoroughly kill MDR bacteria (>99 %) and almost eradicate biofilms through regulating related genetic pathways. This multi-strategy platform integrates potent chemotherapy and near-infrared light-driven NO enhanced auxiliary phototherapy at mild temperature to realize improved antibacterial property. SPAI shows outstanding effect in treatment of MDR bacteria caused skin trauma infection and organic infection (especially sepsis), with satisfactory bactericidal, anti-inflammatory, and immunomodulatory properties in vivo. Owing to excellent biocompatibility, this platform has opened a new avenue for effective treatment of bacterial infectious diseases.

Antimicrobial activity of prophage endolysins against critical Enterobacteriaceae antibiotic-resistant bacteria

Enterobacteriaceae species are part of the 2017 World Health Organization antibiotic-resistant priority pathogens list for development of novel medicines. Multidrug-resistant Klebsiella pneumoniae is an increasing threat to public health and has become a relevant human pathogen involved in life-threatening infections. Phage therapy involves the use of phages or their lytic endolysins as bioagents for the treatment of bacterial infectious diseases. Gram-negative bacteria have an outer membrane, making difficult the access of endolysins to the peptidoglycan. Here, three endolysins from prophages infecting three distinct Enterobacterales species, Kp2948-Lys from K. pneumoniae, Ps3418-Lys from Providencia stuartii, and Kaer26608-Lys from Klebsiella aerogenes, were purified and exhibited antibacterial activity against their specific bacterium species verified by zymogram assays. These three endolysins were successfully associated to liposomes composed of dimyristoyl phosphatidyl choline (DMPC), dioleoyl phosphatidyl ethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS) at a molar ratio (4:4:2), with an encapsulation efficiency ranging from 24 to 27%. Endolysins encapsulated in liposomes resulted in higher antibacterial activity compared to the respective endolysin in the free form, suggesting that the liposome-mediated delivery system enhances fusion with outer membrane and delivery of endolysins to the target peptidoglycan. Obtained results suggest that Kp2948-Lys appears to be specific for K. pneumoniae, while Ps3418-Lys and Kaer26608-Lys appear to have a broader antibacterial spectrum. Endolysins incorporated in liposomes constitute a promising weapon, applicable in the several dimensions (human, animals and environment) of the One Health approach, against multidrug-resistant Enterobacteriaceae.

A H2 S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-guest interactions between a cysteine-responsive cyano-tetraphenylporphyrin (TPP-CN) and a water-soluble carboxylatopillar[5]arene (CP5). TPP-CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti-inflammatory and cell protection capabilities. Under 660nm light irradiation, TPP-CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H2 S from TPP-CN. H2 S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti-inflammatory abilities of TPP-CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.

Self‐assembly multifunctional DNA tetrahedron for efficient elimination of antibiotic‐resistant bacteria

AbstractAntibiotic resistance is a major challenge in the clinical treatment of bacterial infectious diseases. Herein, we constructed a multifunctional DNA nanoplatform as a versatile carrier for bacteria‐specific delivery of clinical antibiotic ciprofloxacin (CIP) and classic nanoantibiotic silver nanoparticles (AgNP). In our rational design, CIP was efficiently loaded in the self‐assembly double‐bundle DNA tetrahedron through intercalation with DNA duplex, and single‐strand DNA‐modified AgNP was embedded in the cavity of the DNA tetrahedron through hybridization. With the site‐specific assembly of targeting aptamer in the well‐defined DNA tetrahedron, the bacteria‐specific dual‐antibiotic delivery system exhibited excellent combined bactericidal properties. With enhanced antibiotic accumulation through breaking the out membrane of bacteria, the antibiotic delivery system effectively inhibited biofilm formation and promoted the healing of infected wounds in vivo. This DNA‐based antibiotic delivery system provides a promising strategy for the treatment of antibiotic‐resistant infections.

Near-infrared II fluorescent carbon dots for differential imaging of drug-resistant bacteria and dynamic monitoring of immune system defense against bacterial infection in vivo

In vivo fluorescence imaging allows the accurate acquisition of dynamic biological information, which plays a vital role in the early diagnosis and treatment of bacterial infectious diseases. Herein, a NIR-II-emitting CD-based nanoprobe (CyCDs) is synthesized using Cy7-CH3 as the carbon source and 3-hydroxytyramine hydrochloride as the surface passivator. Notably, the π-conjugated system and rigid planar structure of the carbon source can broaden the wavelength range of absorption and emission. The presence of amino groups enables CyCDs with a positive zeta potential (+0.32 mV), which can facilitate the interactions between CyCDs and bacteria. Interestingly, CyCDs can only stain the cell wall of drug-resistant bacteria, while normal bacteria have a bright fluorescent signal over all of the cell. This phenomenon enables the identification of drug-resistant bacteria in vitro. Furthermore, CyCDs can be used to monitor the interaction between the immune system and infected bacteria in vivo and guide the timely usage of antibiotics

An Effective Model for Predicting Phage-Host Interactions Via Graph Embedding Representation Learning With Multi-Head Attention Mechanism

In the treatment of bacterial infectious diseases, overuse of antibiotics may lead to not only bacterial resistance to antibiotics but also dysbiosis of beneficial bacteria which are essential for maintaining normal human life activities. Instead, phage therapy, which invades and lyses specific pathogenic bacteria without affecting beneficial bacteria, becomes more and more popular to treat bacterial infectious diseases. For the effective phage therapy, it requires to accurately predict potential phage-host interactions from heterogeneous information network consisting of bacteria and phages. Although many models have been proposed for predicting phage-host interactions, most methods fail to consider fully the sparsity and unconnectedness of phage-host heterogeneous information network, deriving the undesirable performance on phage-host interactions prediction. To address the challenge, we propose an effective model called GERMAN-PHI for predicting Phage-Host Interactions via Graph Embedding Representation learning with Multi-head Attention mechaNism. In GERMAN-PHI, the multi-head attention mechanism is utilized to learn representations of phages and hosts from multiple perspectives of phage-host associations, addressing the sparsity and unconnectedness in phage-host heterogeneous information network. More specifically, a module of GAT with talking-heads is employed to learn representations of phages and bacteria, on which neural induction matrix completion is conducted to reconstruct the phage-host association matrix. Results of comprehensive experiments demonstrate that GERMAN-PHI performs better than the state-of-the-art methods on phage-host interactions prediction. In addition, results of case study for two high-risk human pathogens show that GERMAN-PHI can predict validated phages with high accuracy, and some potential or new associated phages are provided as well.

The High Penetrability of Nanoparticles into Bacterial Membranes: A Key of a Potential Application

Abstract Currently, nanoparticles have gained considerable attention for the treatment of bacterial infectious diseases. The possibility for using this technology as an alternative therapeutic strategy for controlling microbial biofilms, colonizations and infections has been the subject of intense investigations. Even though, the potential toxicity and disadvantage of using nanoparticles, researchers focused on their high penetrability into bacterial membranes, capabilities to disrupt biofilm formation and the role of chemotaxis in this interaction. Face to this significant debate, we discuss the link between metal resistance, bacterial chemotaxis and the promising use of nanoparticles (NP). P. aeruginosa has emerged as a model organism for biofilm studies, the aim of this review is to provide a concise and comprehensive survey of certain relevant aspects related to the research on nanoparticles and these bacteria.

Advances and perspectives for antimicrobial peptide and combinatory therapies.

Antimicrobial peptides (AMPs) have shown cell membrane-directed mechanisms of action. This specificity can be effective against infectious agents that have acquired resistance to conventional drugs. The AMPs' membrane-specificity and their great potential to combat resistant microbes has brought hope to the medical/therapeutic scene. The high death rate worldwide due to antimicrobial resistance (AMR) has pushed forward the search for new molecules and product developments, mainly antibiotics. In the current scenario, other strategies including the association of two or more drugs have contributed to the treatment of difficult-to-treat infectious diseases, above all, those caused by bacteria. In this context, the synergistic action of AMPs associated with current antibiotic therapy can bring important results for the production of new and effective drugs to overcome AMR. This review presents the advances obtained in the last 5years in medical/antibiotic therapy, with the use of products based on AMPs, as well as perspectives on the potentialized effects of current drugs combined with AMPs for the treatment of bacterial infectious diseases.

Complexation of Gold(III) with Pyridoxal 5'-Phosphate-Derived Hydrazones in Aqueous Solution.

Today, complexes of gold(I) and gold(III) are recognized as promising drugs for the treatment of bacterial infectious diseases and oncological diseases, respectively. It is of interest to broaden the area of potential use of gold(III) compounds to the pathogenic microorganism as well. The first step towards the development of new antibacterial drugs based on Au3+ complexes is the study of their stability in an aqueous solution. The present contribution reports on the investigation of gold(III) complexation with five hydrazones derived from a well-known biologically active compound, pyridoxal 5'-phosphate (one of the aldehyde forms of the B6 vitamin). The complex formation in aqueous solutions was confirmed by mass spectrometry and fluorescent spectroscopy. The stoichiometric composition of the complexes formed and their stability constants were determined using a UV-Vis titration method. The complexes are quite stable at physiological values of pH, as the speciation diagrams show. The results of the paper are helpful for further studies of gold(III) complexes interaction with biomacromolecules.

Evaluation of antimicrobial resistance among the clinically isolated S. aureus and E. coli from a hospital in Karachi, Pakistan

The surfacing and extend of antibiotic resistance in different organisms (parasites, fungi, bacteria, and virus) is among the mainly important health troubles of the world today. The battle to antimicrobial drugs has increased at society and mostly at hospital settings. Pan-resistant strains (organisms resistant to all antibiotics), multidrug-resistant (MDR), and extensively drug resistant (XDR) is antibiotic treatment decline and it has amplified morbidity, and mortality, along with important effects on the price of remedial treatment of bacterial infectious diseases. In this study antibiotic resistance of different groups of commonly used antibiotics has been studied for clinically isolated of S.aureus and E.coli grown by Blood, Urine, and Pus samples. All samples have been collected at Memon Medical Institute (MMI) Hospital, Karachi. Sixty-four clinical specimens were tested for their antibiogram pattern with broadly used antibiotics for the treatment of bacterial infections. Results indicated a range of 0 to 100% of antibiotic resistance showing a failure in antibiotic activity against E. coli and S.aureus. Piperacillin + Tazobactam (Ta), Cefoperazone + Sulbactum (Sul), Ciprofloxicin/Ofloxocin, Co-trimoxazole, and Aztreonam (Azactum) were 100% resistance by E.coli isolated from pus samples whereas, S.aureus showed resistance against Erythromycin 60% from pus, Ciprofloxicin/Ofloxocin57.14% from pus and urine, and Meropenem 57.14% from pus.

Synergy of green-synthesized silver nanoparticles and Vatica diospyroides fruit extract in inhibiting Gram-positive bacteria by inducing membrane and intracellular disruption

Silver nanoparticles (AgNPs) are used in biomedicine applications. Other drugs combined with the AgNPs can improve efficacy in the treatment of diseases, and most such studies have focused on antibiotics. We determined the synergistic effects of Phyllanthus emblica-derived AgNPs in combination with Vatica diospyroides cotyledon extracts (VCE) against bacteria using agar well diffusion, broth microdilution, and minimum inhibitory concentration (MIC). Synergy of AgNPs and VCE was confirmed with the fractional inhibitory concentration index (FICI). To evaluate patterns of bacterial death, flow cytometry and electron microscopy were used. We found that the effective incubation time of AgNPs against bacteria was highly variable. Increasing AgNPs in the combination influenced antibacterial activity against Staphylococcus aureus and Bacillus subtilis. The MIC values interpreted through FICI showed synergy against S. aureus and indifference against B. subtilis. Flow cytometric profiles confirmed that the fraction of S. aureus that respond to a combination of VCE with AgNPs increased in dose-dependent manner. The response patterns of bacteria proceeded simultaneously as the cells lost intracellular components and suffered membrane damage. Synergy of AgNPs with a plant extract has become a promising approach, as green AgNPs and plant extracts are biocompatible and cost-effective resources that can utilized for the treatment of bacterial infectious diseases.

Chemical approaches towards installation of rare functional groups in bacterial surface glycans.

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.

Promoted generation of singlet oxygen by hollow-shell CoS/g-C3N4 catalyst for sulfonamides degradation

Sulfanilamide (SM), which is a representative drug of sulfonamides, is commonly used for the prevention and treatment of bacterial infectious diseases and is extremely difficult to remove from water. Herein, an efficient catalyst (CoS/CN) for sulfanilamide degradation was constructed by CoS self-assembling on ultrathin graphitic carbon nitride (g-C3N4) nanosheets. The prepared hollow-shell CoS/CN catalyst could completely degrade SM within 10 min with a rate constant of 2.49 min−1 through the activation of peroxymonosulfate (PMS). Experiments and theoretical calculations indicated that S2− acted as an electron donor for promoting the generation of Co(II). The combination of g-C3N4 and CoS made the CoS/CN composite have higher conductivity and electron transfer ability than CoS, which promoted the decomposition of PMS to produce reactive oxygen species (ROSs). Singlet oxygen (1O2) was proved as the primary ROSs, and SO4− radicals were generated during the 1O2-dominated degradation process to improve the low mineralization rate. 1O2 and SO4− were derived from the oxidation of PMS and the electron transfer of g-C3N4. The results revealed the synergistic effect of free radicals and non-free radicals during the redox of PMS, and provided theoretical support for the efficient degradation of refractory organics in wastewater.

Limitations of Phage Therapy and Corresponding Optimization Strategies: A Review.

Bacterial infectious diseases cause serious harm to human health. At present, antibiotics are the main drugs used in the treatment of bacterial infectious diseases, but the abuse of antibiotics has led to the rapid increase in drug-resistant bacteria and to the inability to effectively control infections. Bacteriophages are a kind of virus that infects bacteria and archaea, adopting bacteria as their hosts. The use of bacteriophages as antimicrobial agents in the treatment of bacterial diseases is an alternative to antibiotics. At present, phage therapy (PT) has been used in various fields and has provided a new technology for addressing diseases caused by bacterial infections in humans, animals, and plants. PT uses bacteriophages to infect pathogenic bacteria so to stop bacterial infections and treat and prevent related diseases. However, PT has several limitations, due to a narrow host range, the lysogenic phenomenon, the lack of relevant policies, and the lack of pharmacokinetic data. The development of reasonable strategies to overcome these limitations is essential for the further development of this technology. This review article described the current applications and limitations of PT and summarizes the existing solutions for these limitations. This information will be useful for clinicians, people working in agriculture and industry, and basic researchers.

Advances in the Application of Nanomaterials as Treatments for Bacterial Infectious Diseases

Bacteria-targeting nanomaterials have been widely used in the diagnosis and treatment of bacterial infectious diseases. These nanomaterials show great potential as antimicrobial agents due to their broad-spectrum antibacterial capacity and relatively low toxicity. Recently, nanomaterials have improved the accurate detection of pathogens, provided therapeutic strategies against nosocomial infections and facilitated the delivery of antigenic protein vaccines that induce humoral and cellular immunity. Biomaterial implants, which have traditionally been hindered by bacterial colonization, benefit from their ability to prevent bacteria from forming biofilms and spreading into adjacent tissues. Wound repair is improving in terms of both the function and prevention of bacterial infection, as we tailor nanomaterials to their needs, select encapsulation methods and materials, incorporate activation systems and add immune-activating adjuvants. Recent years have produced numerous advances in their antibacterial applications, but even further expansion in the diagnosis and treatment of infectious diseases is expected in the future.

A 'time bomb' in the human intestine-the multiple emergence and spread of antibiotic-resistant bacteria.

Antibiotics have a strong killing effect on bacteria and are the first choice for the prevention and treatment of bacterial infectious diseases. Therefore, they have been widely used in the medical field, animal husbandry and planting industry. However, with the massive use of antibiotics, more and more antibiotic-resistant bacteria (ARB) have emerged. Because human intestines are rich in nutrients, have suitable temperature, and are high in bacterial abundance, they can easily become a hotbed for the spread of ARB and antibiotic-resistant genes (ARGs). When opportunistic pathogenic bacteria in the intestine acquire ARGs, the infectious diseases caused by such opportunistic pathogens will become more difficult to treat, or even impossible to cure. Therefore, ARB in the human intestine are like a 'time bomb'. In this review, we discuss the sources of intestinal ARB and the transmission routes of ARGs in the human intestine from the perspective of One Health. Further, we describe various methods to prevent the emergence of ARB and inhibit the spread of ARGs in the human intestine. Finally, we may be able to overcome ARB in the human intestine using an interdisciplinary 'One Health' approach.

Biomaterial-based delivery of antimicrobial therapies for the treatment of bacterial infections.

The development of antibiotic tolerance and resistance has demanded the search for alternative antibacterial therapies. This Review discusses antibacterial biomaterials and biomaterial-assisted delivery of non-antibiotic therapeutics for the treatment of bacterial infectious diseases, with a focus on clinical translation.

Aktivitas Antibakteri Ekstrak Etanol Daun Bandotan (Ageratum Conyzoides L.) Terhadap Bakteri Streptococcus Pyogenes

The treatment of bacterial infectious diseases using a semi synthetic antibiotic can lead to resistance, so that the search is necessary to overcome it the ingredients of natural medicine from plants, one of them namely bandotan leaf extract (Ageratum conyzoides l.). This research aims to identify the chemical compounds contained in leaf bandotan and knowing his activity as antibacterial against Pseudomonas aeruginosa and s. pyogenes. The leaves are extracted in bandotan maceration using solvent ethanol 96%. The extract was tested using the method of antibacterial activity of sumuran and clear zones are measured that is formed using a caliper and triplo. The results of the identification of a compound leaf bandotan secondary metabolite showed a group of compounds alkaloids, saponins, tannins, flavonoids, phenolic, triterpenoid glycosides, steroids,. Based on a test of antibacterial activity against s. pyogenes with the concentration of 100%, 50%, 25%, 12.5%, 6.25% showed a clear zone on the concentration in a row with an average of 14.52 mm; 13.87 mm; 13.38 mm; 12.38 mm; 11.75 mm; 15.33 mm. While testing the antibacterial activity against Pseudomonas aeruginosa with the same concentrations did not show the presence of antibacterial activity of extracts of leaves of bandotan with no clear zone formation

Colloidal silver combating pathogenic Pseudomonas aeruginosa and MRSA in chronic rhinosinusitis

The emergence of antibiotic resistant bacteria requires for the development of new antimicrobial compounds one of which colloidal silver (CS) having strong bactericidal properties and being the most promising inorganic nanoparticles for the treatment of bacterial infectious diseases. However, their production can be slow and cumbersome. Here, we used Corymbia maculata aqueous leaf extract as a reducing agent to synthesize CS in a single 15-minute process. CS was physico-chemically characterized for shape, size, zeta potential and stability. The Minimal Inhibitory Concentration (MIC) and Minimum Biofilm Eradication Concentration (MBEC) of CS against planktonic and biofilm forms of methicillin-resistant Staphylococcus aureus (MRSA, n = 5), Pseudomonas aeruginosa (n = 5), Haemophilus influenzae (n = 5) and Streptococcus pneumoniae (n = 3) chronic rhinosinusitis clinical isolates were investigated using the microdilution method and resazurin assay, respectively. The in vitro cytotoxicity on bronchial epithelial cells (Nuli-1) was analyzed by the crystal violet proliferation assay. The safety and efficacy of CS was evaluated in an in vivo infection model in Caenorhabditis elegans. CS was spherical in shape with a diameter of between 11−16 nm (TEM analysis) in dried form and 40 nm (NanoSight) in colloidal form and was stable at room temperature and 4 °C for one year. Average MIC and MBEC values varied between 11 and 44 ppm for MRSA, H. influenzae and S. pneumoniae and between 0.2 and 3 ppm for P. aeruginosa. CS was not toxic to Nuli-1 cells or C. elegans at concentrations of 44 ppm and reduced the Colony Forming Units counts by 96.9 % and 99.6 % in C. elegans for MRSA and P. aeruginosa, respectively. In conclusion, a novel, green synthesis of stable CS is demonstrated with good safety and efficacy profiles, particularly against P. aeruginosa in planktonic and biofilm forms. These CS have potential applications against clinical infections, including in the context of CRS.

Facile synthesis of tannic acid modified NbTe2 nanosheets for effective photothermal ablation of bacterial pathogens

Photothermal antibacterial methods are urgently needed in the treatment of bacterial infectious diseases and drug-resistant bacteria, which is due to the abuse of antibiotics leading to the production of drug-resistant bacteria, resulting in poor treatment of diseases. However, it is very challenging to improve the yield of nanomaterial preparation and surface modification, while also ensuring the enhancement of antibacterial properties. Herein, we report a tannic acid-assisted peeling method to prepare a single-layer tannic acid (TA) modified NbTe2 nanosheets (NbTe2/TA) with high production yield (≈ 52 ± 10%) and multiple antibacterial properties. NbTe2/TA nanosheets show uniform particle size and ultra-thin thickness. In near-infrared light, NbTe2/TA demonstrates excellent photothermal conversion performance and photothermal stability, further demonstrating the potential of NbTe2/TA for photothermal antibacterial applications. It is worth noting that TA has excellent antibacterial properties, which can further enhance the photothermal antibacterial properties of NbTe2/TA. Moreover, NbTe2/TA has been shown to have good biosecurity which does not damage epithelium and fibroblasts. To the best of our knowledge, the above NbTe2 stripping method is superior to the previously reported NbTe2 peeling method and is the first time applied to the study of photothermal antibacterial.