Pathogenic Bacterial Infections Research Articles

Phytochemical Screening and Antibacterial Activities of Dillenia indica and Ficus exasperata

It has been proven that antimicrobials of plant origin work more efficiently with fewer side effects. This study aimed to identify the phytochemicals in extracts of Dillenia indica and Ficus exasperata and also to examine their antibacterial effect on clinical bacterial isolates (Escherichia coli, Staphylococcus aureus and Streptococcus pyogenes). Dry leaves of D. indica and F. exasperata were extracted in ethanol, methanol, distilled water and hot water. The 100% extract solution was further diluted to different concentrations (75%, 50%, and 25%). The extracts were concentrated using a rotary evaporator. Using the agar well diffusion method, the isolates were subjected to the antibacterial action of various concentrations of these extracts. The diameter of the zones of inhibition were measured in millimeters. The data obtained were analyzed by Analysis of Variance (ANOVA) to determine significant (P<0.05) effects. Significant differences between means were determined using Duncan’s Multiple Range Test (DMRT). The phytochemical screening indicated the presence of alkaloids, phenols, glycosides, flavonoids, saponins, quinones, and anthrax quinones. Terpenoids were absent. The extracts of the plants inhibited the growth of the bacteria tested with varied effectiveness. The diameter of the zones of inhibition were concentration dependent in all extracts. The maximum antibacterial activities were observed in the organic solvent extracts. When the activity of the plant extract was compared with that of the standard antibiotics used in this work, it was observed that the plant extract compared favourably with those of these standard antibiotics. In conclusion, the results showed that leaf extract of D. indica and F. exasperata have antibacterial activity. Based on the antibacterial activity of D. indica and F. exasperata extracts as revealed by this research, the extracts of these plants can be used in the development of new pharmaceuticals which can be useful as strong therapeutic agent against bacterial pathogenic infections.

Thymidine starvation promotes c-di-AMP-dependent inflammation during pathogenic bacterial infection

Antimicrobials can impact bacterial physiology and host immunity with negative treatment outcomes. Extensive exposure to antifolate antibiotics promotes thymidine-dependent Staphylococcus aureus small colony variants (TD-SCVs), commonly associated with worse clinical outcomes. We show that antibiotic-mediated disruption of thymidine synthesis promotes elevated levels of the bacterial second messenger cyclic di-AMP (c-di-AMP), consequently inducing host STING activation and inflammation. An initial antibiotic screen in Firmicutes revealed that c-di-AMP production was largely driven by antifolate antibiotics targeting dihydrofolate reductase (DHFR), which promotes folate regeneration required for thymidine biosynthesis. Additionally, TD-SCVs exhibited excessive c-di-AMP production and STING activation in a thymidine-dependent manner. Murine lung infection with TD-SCVs revealed STING-dependent elevation of proinflammatory cytokines, causing higher airway neutrophil infiltration and activation compared with normal-colony S. aureus and hemin-dependent SCVs. Collectively, our results suggest that thymidine metabolism disruption in Firmicutes leads to elevated c-di-AMP-mediated STING-dependent inflammation, with potential impacts on antibiotic usage and infection outcomes.

Gastric Cancer and Viruses: A Fine Line between Friend or Foe.

Gastric cancer (GC) is a significant health concern worldwide, with a GLOBOCAN estimate of 1.08 million novel cases in 2020. It is the leading cause of disability-adjusted life years lost to cancer, with the fourth most common cancer in males and the fifth most common cancer in females. Strategies are pursued across the globe to prevent gastric cancer progression as a significant fraction of gastric cancers have been linked to various pathogenic (bacterial and viral) infections. Early diagnosis (in Asian countries), and non-invasive and surgical treatments have helped manage this disease with 5-year survival for stage IA and IB tumors ranging between 60% and 80%. However, the most prevalent aggressive stage III gastric tumors undergoing surgery have a lower 5-year survival rate between 18% and 50%. These figures point to a need for more efficient diagnostic and treatment strategies, for which the oncolytic viruses (OVs) appear to have some promise. OVs form a new therapeutic agent class that induces anti-tumor immune responses by selectively killing tumor cells and inducing systemic anti-tumor immunity. On the contrary, several oncogenic viruses have been shown to play significant roles in malignancy progression in the case of gastric cancer. Therefore, this review evaluates the current state of research and advances in understanding the dual role of viruses in gastric cancer.

Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan-indocyanine green/luteolin nanocomposites for wound healing.

Despite the success, it is highly challenging to battle against pathogenic biofilms-based chronic bacterial infections by conventional antibiotic therapy. Herein, we report a near-infrared (NIR)/acid-induced nanoplatform based on chitosan (CS)-coated indocyanine green (ICG, photosensitizer)/luteolin (LUT, a natural quorum sensing inhibitor) nanocomposites (ICG/LUT-CS) as antibacterial and antibiofilm agents for skin wound healing. Initially, the ICG/LUT nanoplatforms are prepared by the supercritical antisolvent technology and coated with the CS layer. The obtained ICG/LUT-CS with ultra-high encapsulation efficiency exhibited more favorable photothermal conversion effects and improved NIR laser/acid dual-induced drug release behavior than individual modalities, achieving exceptional bacteria-killing and biofilm elimination effects. Moreover, the ICG/LUT-CS realized the synergetic effects of chemotherapy and photothermal therapy outcomes for wound healing. Together, our findings provided an appealing strategy for the rapid preparation and future translational application of ICG/LUT-CS as an ideal agent for fighting against biofilm infections.

Paravertebral abscess and bloodstream infection caused by Burkholderia pseudomallei after acupuncture: a case report

BackgroundVarious pathogenic bacterial infections caused by acupuncture have raised widespread concern, but paravertebral abscesses and bloodstream infections of Burkholderia pseudomallei (B.pseudomallei) after acupuncture have not been reported.Case presentationA 49-year-old man was admitted to hospital with recurrent back pain and fever for 1 month, along with the finding of undiagnosed diabetes. He was considered to have tuberculosis because of unrelieved high fever and pulmonary nodules. Bilateral blood culture suggested B.pseudomallei infection, MRI of the lumbar spine suggested paravertebral abscess, and the final diagnosis was paravertebral abscess and bloodstream infection after acupuncture combined with migrating lung infection. He was discharged after abscess debridement and intensive anti-infective therapy, but no further oral antibiotics were administered because of his poor adherence. More than 5 months later, he was readmitted with the urine culture findings of B.pseudomallei. No other abscess formation was observed and he received oral antibiotics for more than 3 months without recurrence.ConclusionsAcupuncture may lead to B.pseudomallei infection in high-risk groups, and inadequate treatment can lead to recurrent infections.

SNARE SYP132 mediates divergent traffic of plasma membrane H+-ATPase AHA1 and antimicrobial PR1 during bacterial pathogenesis.

The vesicle trafficking SYNTAXIN OF PLANTS132 (SYP132) drives hormone-regulated endocytic traffic to suppress the density and function of plasma membrane (PM) H+-ATPases. In response to bacterial pathogens, it also promotes secretory traffic of antimicrobial pathogenesis-related (PR) proteins. These seemingly opposite actions of SYP132 raise questions about the mechanistic connections between the two, likely independent, membrane trafficking pathways intersecting plant growth and immunity. To study SYP132 and associated trafficking of PM H+-ATPase 1 (AHA1) and PATHOGENESIS-RELATED PROTEIN1 (PR1) during pathogenesis, we used the virulent Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) bacteria for infection of Arabidopsis (Arabidopsis thaliana) plants. SYP132 overexpression suppressed bacterial infection in plants through the stomatal route. However, bacterial infection was enhanced when bacteria were infiltrated into leaf tissue to bypass stomatal defenses. Tracking time-dependent changes in native AHA1 and SYP132 abundance, cellular distribution, and function, we discovered that bacterial pathogen infection triggers AHA1 and SYP132 internalization from the plasma membrane. AHA1 bound to SYP132 through its regulatory SNARE Habc domain, and these interactions affected PM H+-ATPase traffic. Remarkably, using the Arabidopsis aha1 mutant, we discovered that AHA1 is essential for moderating SYP132 abundance and associated secretion of PR1 at the plasma membrane for pathogen defense. Thus, we show that during pathogenesis SYP132 coordinates AHA1 with opposing effects on the traffic of AHA1 and PR1.

Clinical characteristics of Gram-negative and Gram-positive bacterial infection in acute cholangitis: a retrospective observational study

BackgroundTo investigate the difference in the severity of illness, organ dysfunction, and prognosis of acute cholangitis due to different pathogenic bacterial infection types.MethodsA retrospective observational study was performed. Patients who met the selection criteria according to blood culture and bile culture results of different pathogenic bacterial were divided into groups. The severity of illness, organ dysfunction, and prognosis of the groups were analyzed and compared comprehensively.ResultsA total of 424 patients were included, and no bacterial growth developed in 111 patients (26.2%). Among the 313 patients (73.8%) with bacterial growth, 155 patients had only Gram-negative bacteria cultured (49.5%), 48 patients had only Gram-positive bacteria cultured (15.3%), and 110 patients had both Gram-negative and Gram-positive bacteria cultured (35.1%). The proportion of Grade III patients and the APACHE II and SOFA scores of the mixed Gram-negative and positive group were the highest (p < 0.05); the intensive care unit admission day and hospital stay were longer, and the mortality rate were also higher 20/110 (18.2%) than the other two groups. Regression analysis showed that bacterial growth was an independent risk factor for organ dysfunction. The risks of an increased septic shock, neurological dysfunction, hepatic dysfunction, hematological dysfunction, and respiratory dysfunction in the mixed Gram-negative and positive group were higher than the Gram-negative group (P < 0.05). The Cox proportional hazards regression prompt showed that different culture results were independent risk factors for death. The mixed Gram-negative and positive group had increased hazard ratios and 95% CI of 7.30 (95% CI 1.55 to 34.38) compared with the Gram-negative group. There was no difference between the Gram-negative group and the Gram-positive group in the severity of illness, organ dysfunction, intensive care unit admission day, hospital stay, mortality rate, and risk of death (P > 0.05).ConclusionsIn acute cholangitis, mixed infection with Gram-negative and Gram-positive bacteria was more severe and was associated with a higher risk of death. There were no apparent differences between Gram-negative and Gram-positive bacterial infections.

Functionalized Mn3 O4 Nanosheets with Photothermal, Photodynamic, and Oxidase-Like Activities Triggered by Low-Powered Near-Infrared Light for Synergetic Combating Multidrug-Resistant Bacterial Infections.

Multidrug-resistant (MDR) pathogenic bacterial infections have become a major danger to public health. Synergetic therapy through multiple approaches is more powerful than the respective one alone, but has been rarely achieved in defeating MDR bacterial infections so far. Herein, indocyanine green-functionalized Mn3 O4 nanosheets are engineered as an efficient and safe antibacterial agent with photothermal, photodynamic, and oxidase-like activities, which display powerful ability in treating MDR bacterial infections. Therein, photothermal and photodynamic activities can be triggered by a single low-powered near-infrared laser (808nm, 0.33 W cm-2 ), resulting in the generation of localized hyperthermia (photothermal conversion efficiency, 67.5%) and singlet oxygen. Meanwhile, oxidase-like activity of this material further leads to the generation of hydroxyl radical as well as superoxide radical. Sheet-like structure with rough surfaces make them tends to adhere on bacterial surface and thus damage membrane system as well as influence bacterial metabolism. As a result, Gram-positive and Gram-negative bacteria can both be eradicated. Animal experiments further indicate that the functionalized Mn3 O4 nanosheets can effectively treat methicillin-resistant Staphylococcus aureus-infected wounds through the triple synergetic therapy. Moreover, toxicity evaluation in vitro and in vivo has proved the superior biosafety of this material, which is promising to apply in clinical anti-infective therapy.

Ti-MOF-based biosafety materials for efficient and long-life disinfection via synergistic photodynamic and photothermal effects

Pathogenic bacterial infection is severely threatening public health globally. The multi-modal antibacterial nanoplatforms could significantly improve the antibacterial efficiency. Here, we report a metal(Ti)-organic framework (MOF) derived nanocarbon (C-Ti-MOF) as a biosafety material for synergistic sterilization of pathogenic bacteria via efficient photodynamic catalysis and robust photothermal effects. The C-Ti-MOF consists of abundant TiO2 nanodots embedded in graphitic carbon frameworks. Under visible light irradiation, TiO2 nanodots can catalyze H2O2 and O2 to produce superoxide anion (•O2–) and singlet oxygen (1O2), respectively. Meanwhile, under near-infrared irradiation (NIR), C-Ti-MOF can generate massive heat to destroy bacterial membranes. Systematic antibacterial experiments reveal that the C-Ti-MOF nanoagents have a long-lasting and nearly 100% bactericidal ratio at an extremely low dose (0.16 mg/mL), which is much better than the state-of-the-art TiO2 (Commercial TiO2 (P25), 0.64 mg/mL). Furthermore, the C-Ti-MOF can be electrospun into an antibacterial nanofiber membrane via mixing with polymeric matrix for treating bacteria-contaminated wastewater, and the membranes possess integrated antibacterial activity and excellent biocompatibility. Our study demonstrates a promising Ti-MOF-based biosafety material for efficient and long-life disinfection, which may stimulate new research in MOF-related biological applications in various disciplines ranging from water decontaminations to nanotherapeutics.

Antibacterial Cascade Catalytic Glutathione-Depleting MOF Nanoreactors.

Nanozymes with peroxidase-like activity have great application potential in combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, the near-neutral pH and high glutathione (GSH) levels in the bacterial infection microenvironment severely limit their applications in antibacterial therapy. In this work, a metal-organic framework (MOF)-based cascade catalytic glutathione-depleting system named MnFe2O4@MIL/Au&GOx (MMAG) was constructed. The MMAG cascade-catalyzed glucose to provide H+ and produces a large amount of toxic reactive oxygen species. In addition, MMAG consumed GSH, which can result in bacterial death more easily. Systematic antibacterial experiments illustrated that MMAG has superior antibacterial effects on both Gram-positive bacteria and Gram-negative bacteria.

Green Synthesis of Silver-Carbon Nanocomposites with Extraordinary Stability and Robust Antibacterial Activity against Bacterial Diseases in Fish.

Pathogenic bacterial infections in freshwater-farmed fish have high morbidity and mortality. As an effective broad spectrum antibacterial agent, silver nanoparticles (AgNPs) have great application potential in the field of aquaculture. However, due to the easy aggregation and oxidation properties of AgNPs, their practical applications are rather limited. Herein, nanocomposites of AgNPs and carbon nanodots (AgNPs@C-dots) were synthesized by using carbon nanodots as a reductant and a stabilizer. Their antibacterial activity and biosafety were systematically investigated. AgNPs@C-dots exhibit superior aggregation stability, excellent biocompatibility, and enhanced antibacterial activity compared to common AgNPs (reduced by sodium citrate). In vitro antibacterial results show that AgNPs@C-dots can completely kill Aeromonas salmonicida at a concentration of 9.5 μg mL-1. The possible antibacterial mechanism of AgNPs@C-dots was thoroughly clarified by scanning electron microscopy, gel imaging, and laser scanning confocal imaging. The AgNPs@C-dots have been successfully applied to enhance the resistance of zebrafish to A. salmonicida with satisfactory results. Moreover, AgNPs@C-dots did not result in detectable residues of silver in the muscles after 30 days of exposure. It is well demonstrated that AgNPs@C-dots could be used for the development of antibacterial agents in aquaculture.

ANTIBACTERIAL EFFECTS OF EXTRACTS FROM Tanacetum parthenium L. LEAVES

In our current study, phytochemical analysis and antibacterial activity of leaf extracts of T. parthenium were assessed. Qualitative phytochemical screening was carried using standard procedures and quantitative analysis for estimation of total phenolic content (TPC) was determined by spectrophotometric method. The antibacterial activity was accomplished using disc diffusion assay, determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against two gram positives (Streptococcus pyogenes (ATCC 19615), Streptococcus anginosus) and two gram negatives (Pseudomonas aeruginosa (ATCC 27853) and Fusobacterium necrogenes) pathogenic bacteria. Preliminary phytochemical analysis of the plant extracts revealed the presence of phenolics, tannins, flavonoids, terpenoids, and cardiac glycosides. The methanol extract had highest total phenolic content (6.17 ± 0.19 mg/ml). The results also displayed that the methanol extract exhibited significant antibacterial activity against the tested pathogenic microorganisms, in particular against S. anginosus with inhibition zone of 15.33±0.33 mm. The lowest MIC (33.33 mg/ml) and MBC (41.66 g/ml) values were observed in methanol extract against S. anginosus and S. pyogenes respectively. The results indicated that crude leaf extracts of T. parthenium had a potent antibacterial activity suggesting that it could be valuable in treating pathogenic bacterial infections.

Photo-excited antibacterial poly(Ɛ-caprolactone)@MoS2/ZnS hybrid nanofibers

The rapid and timely sterilization is quite important function for textiles to prevent human being from pathogenic bacterial infections. Hence, it is necessary to develop wearable fabrics with rapid and effective antibacterial properties. In this work, using one-step hydrothermal method and electrospinning, we synthesized biocompatible antibacterial hybrid nanofibers composed of poly(Ɛ-caprolactone) (PCL) incorporated with heterojunction of MoS2/ZnS (MZ). The MZ endowed the PCL-MZ nanofibers with excellent photothermal and photocatalytic properties under visible light. After 10 min visible light irradiation, the hybrid nanofibers with optimum proportion achieved an effective antibacterial efficacy of 96.03% and 99.09% against Staphylococcus aureus and Escherichia coli, respectively. The underlying mechanism is based on the synergistic effects of reactive oxygen species (ROS) and hyperthermia. Thus, the PCL-MZ hybrid nanofibers will be promising for the fabrication of wearable antibacterial fabrics.

Antibacterial activity of endophytic fungi isolated from the stem bark of jambu mawar (Syzygium jambos)

Abstract. ‘Aini K, Elfita, Widyajanti H, Setiawan A, Kurniawati AR. 2021. Antibacterial activity of endophytic fungi isolated from the stem bark of jambu mawar (Syzygium jambos). Biodiversitas 23: 521-532. Syzygium jambos (jambu mawar) is widely used in South Sumatra as a traditional medicine to treat various diseases, including pathogenic bacterial infections. Literature studies report that parts of S. jambos have been used worldwide for treating diarrhea accompanied by fever, dysentery, sore throat, diabetes, and other infectious diseases. Endophytic fungi isolated from medicinal plants have high diversity, and the biological activity of their secondary metabolites is associated with their host. Therefore, this study aimed to determine the diversity of endophytic fungi from the stem bark of S. jambos and the antibacterial activity of secondary metabolites of endophytic fungi. Fungal isolates with high antibacterial activity were identified to obtain fungal species, and the structure of their compounds was determined. The disc diffusion method carried the antibacterial activity test against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Salmonella typhi) bacteria. Characteristics of endophytic fungi were identified microscopically and macroscopically. Active endophytic fungi were identified by molecular analysis of the internal transcribed region (ITS) of the ribosomal DNA. Isolation of antibacterial compounds using chromatographic techniques and determination of chemical structures using spectroscopy was performed. Eight endophytic fungi were obtained from the stem bark of S. jambos, namely SJ1–SJ8. The endophytic fungus SJ6 showed the highest activity and base on phylogenetic analysis, was identified as Fusarium verticillioides. Pure compounds isolated as yellowish-white solids showed good antibacterial activity against S. aureus and S. typhi with minimum inhibitory concentration values of 64 g/mL each. Based on 1D and 2D nuclear magnetic resonance spectroscopic analysis, compound 1 was identified as 3-hydroxy-4-(hydroxy(4-hydroxyphenyl)methyl)dihydrofuran-2-on.

A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection.

Multimodal synergistic bactericidal agents display great potential for fighting biofilm infections. However, the rational design of biofilm microenvironment (BME)-activatable therapeutic agents with excellent specificities, effective eradications and minimal side effects remains a great challenge. Herein, we show a BME-responsive one-for-all bactericidal nanoplatform consisting of Fe3+-doped polydopamine (Fe/PDA)-capped ZnO nanoparticles with a successive assembly of methylene blue (MB) and poly(ethylene glycol) (PEG). In an acidic BME (pH 5.5), the constructed nanoagent (ZnPMp) can realize the co-delivery of dual metal ions (Zn2+ and Fe3+) and MB, and the latter shows an activated photodynamic antibacterial activity when irradiated with 635 nm laser. Zn2+ produced from acid-sensitive dissolution of ZnO is an effective chemical antibacterial agent. Additionally, the released Fe3+ is reduced to Fe2+ by glutathione (GSH) overexpressed in the BME to generate Fe2+/Fe3+ redox couples, which exhibit Fenton catalytic activity to convert endogenous H2O2 to hydroxyl radicals (˙OH) for chemodynamic sterilization and GSH depletion ability to improve ˙OH-induced oxidative damage. Interestingly, the hyperthermia caused by the Fe/PDA layer assisted with 808 nm laser can damage directly bacterial cells, accelerate the release of Zn2+, Fe3+and MB, and promote the catalytic activity of Fe2+/Fe3+ redox couples for photothermal-augmented multimodal antibiofilm therapy. With the help of dual lasers, ZnPMp displays the broad-spectrum antibacterial effect, inhibits effectively the formation of biofilms, and more importantly eliminates bacteria deep in mature biofilms. In addition, ZnPMp can be used to treat biofilm-related infections in vivo with excellent therapeutic performance and minimal toxicity. Overall, the developed ZnPMp may serve as a potential nano-antibacterial agent for intensive anti-infective therapy.

In vitro and in vivo efficacy of green synthesized AgNPs against Gram negative and Gram positive bacterial pathogens

Global threat of mortality and morbidity increasing due to pathogenic bacterial infection and disease become a significant concern for human population. Development of multidrug resistant bacterial pathogens has increased the search of alternative to conventional antibiotics and small molecules. Metallic nanoparticles are rapidly growing in the field of biomedicine, bioremediation, and bioengineering. Metallic nanoparticles synthesized using plant extract gives an upper edge against toxicity and efficacy of the materials. Silver and silver salt is practised in health organization around the world for killing bacterial pathogens. The present study, one-pot synthesized Rubella tuberosa mediated silver nanoparticles (RT-AgNPs) for the inhibition of ESKAPE panel of bacterial pathogens especially Staphylococcus aureus and Pseudomonas aeruginosa. The Minimal Inhibitory Concentration (MIC) of RT-AgNPs was determined as 4 μg/mL against both pathogens, while the Biofilm Inhibitory concentration (BIC) was determined as 4 μg/mL and 16 μg/mL against Gram negative (P. aeruginosa) and Gram positive (S. aureus) pathogens. The synergy of RT-AgNPs with conventional antibiotics showed the better efficacy with Vancomycin and Gentamicin against S. aureus and P. aeruginosa respectively. Further haemolytic activity of RT-AgNPs against human red blood cell confirmed the non-toxicity at the higher concentration of 64 μg/mL. Thus, RT-AgNPs prove to be suitable candidate for the inhibition of biofilm and pathogenicity of Gram negative and Gram positive pathogens.

Biodiversity and antibacterial activity of endophytic fungi isolated from jambu bol (Syzygium malaccense)

Abstract. Hapida Y, Elfita, Widjajanti H, Salni. 2021. Biodiversity and antibacterial activity of endophytic fungi isolated from jambu bol (Syzygium malaccense). Biodiversitas 22: 5668-5677. Infectious diseases caused by pathogenic bacteria are still high. The existence of bacterial resistance to antibiotics makes it necessary to search for new antibacterial substances from plants and microorganisms. Syzygium malaccense (L.) Merr and Perry (Myrtaceae), known as jambu bol, has been used as a traditional medicine in Indonesia and other countries. It is used to treat pathogenic bacterial infections. Therefore, this study aims to determine the diversity of endophytic fungi and their potential as antibacterial compound sources compared to their host plants. Specifically, screening for endophytic fungi that have antibacterial activities is intended. In this study, endophytic fungi were isolated from the leaves, stem bark, and root bark of the host plants. Each isolate was identified morphologically and cultivated in potato dextrose broth (PDB) medium for four weeks. After the incubation period, the liquid culture was extracted with ethyl acetate and evaporated to obtain a concentrated extract. The Kirby-Bauer method was used to evaluate the antibacterial activity of each endophytic fungal extract and the host plant parts extract. The concentration used was 400µg/mL and the antibiotic was used as a positive control (Tetracycline) is 30µg/mL. Seven endophytic fungi were isolated from the leaves (YD1, YD2, YD3, YD4, YD6, YD7, Y2D1), seven from the stem bark (YB1, YB2, YB3, YB4, YB5, Y2B5, and Y2B6 ), and six from the root bark (YA1, YA2, YA3, YA4, YA5, Y2A2). The endophytic fungi were morphologically identified, and the isolates were shown to be dominated by genera from the Ascomycota (e.g., Poaceascoma, Cladorrhinum, Penicillium, Madurella, Phytophthora, Phialemonium, Monascus, Trichoderma, Ramophialophora, Gliocladium, Wiesneriomyces) and the Zygomycota (e.g., Mucor, Mortierella, and Gongronella) phyla. The fungi isolates Y2D1, YB1, and YA4 were shown to have the highest (strong) antibacterial activity equivalent to their hosts in the performed screening. Endophytic fungi have significant and continued antibacterial activities that have been identified molecularly.

Isolation and Characterization of Novel Phages Targeting Pathogenic Klebsiella pneumoniae.

Klebsiella pneumoniae is a dominant cause of community-acquired and nosocomial infections, specifically among immunocompromised individuals. The increasing occurrence of multidrug-resistant (MDR) isolates has significantly impacted the effectiveness of antimicrobial agents. As antibiotic resistance is becoming increasingly prevalent worldwide, the use of bacteriophages to treat pathogenic bacterial infections has recently gained attention. Elucidating the details of phage-bacteria interactions will provide insights into phage biology and the better development of phage therapy. In this study, a total of 22 K. pneumoniae isolates were assessed for their genetic and phenotypic relatedness by multi-locus sequence typing (MLST), endonuclease S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and in vitro antibiotic susceptibility testing. In addition, the beta-lactamase gene (bla KPC) was characterized to determine the spread and outbreak of K. pneumoniae carbapenemase (KPC)-producing enterobacterial pathogens. Using these ST11 carbapenem-resistant K. pneumoniae isolates, three phages (NL_ZS_1, NL_ZS_2, and NL_ZS_3) from the family of Podoviridae were isolated and characterized to evaluate the application of lytic phages against the MDR K. pneumoniae isolates. In vitro inhibition assays with three phages and K. pneumoniae strain ZS15 demonstrated the strong lytic potential of the phages, however, followed by the rapid growth of phage-resistant and phage-sensitive mutants, suggesting several anti-phage mechanisms had developed in the host populations. Together, this data adds more comprehensive knowledge to known phage biology and further emphasizes their complexity and future challenges to overcome prior to using phages for controlling this important MDR bacterium.

Pillar[5]arene-Based Acid-Triggered Supramolecular Porphyrin Photosensitizer for Combating Bacterial Infections and Biofilm Dispersion.

The treatment of pathogenic bacterial infection has long been the most serious threat to human life and attracted widespread attention. Herein, a supramolecular photosensitizer platform based on carboxylatopillar[5]arene (CP5) and tetrafluorophenyl porphyrin functionalized with a quaternary ammonium group (TFPP-QA) for combating bacteria and dispersing biofilm via photodynamic treatment is constructed. By introducing the host macrocycle CP5 and host-guest interaction, the supramolecular photosensitizer has great biocompatibility and acid responsiveness. On the one hand, the acid-triggered dissociation of TFPP-QA/CP5 could induce the porphyrin photosensitizer to target bacterial cells and disrupt the charge balance of bacterial membranes, enhance the permeability of the bacterial membrane. On the other hand, the TFPP-QA/CP5 antibacterial platform possesses superb reactive oxygen species (ROS) generation capability under light irradiation, leading to enhanced photodynamic antibacterial efficacy. The in vitro and in vivo studies show that the supramolecular photosensitizers exhibit high antibacterial efficiency and biofilm dissipation effect under 660nm light irradiation. Therefore, it is anticipated that the rational design and integration of photosensitizers and quaternary ammonium compounds through the supramolecular strategy would provide a promising prospect for clinical photodynamic antimicrobial therapy.

Negatively Charged Sulfur Quantum Dots for Treatment of Drug-Resistant Pathogenic Bacterial Infections.

Drug-resistant pathogenic bacteria as a worldwide health threat calls for valid antimicrobial agents and tactics in clinical practice. Positively charged materials usually achieve antibacteria through binding and disrupting bacterial membranes via electrostatic interaction, however, they also usually cause hemolysis and cytotoxicity. Herein, we engineered negatively charged sulfur quantum dots (SQDs) as an efficient broad-spectrum antibiotic to kill drug-resistant bacteria in vitro and in vivo. The SQDs can destroy the bacterial membrane system and affect their metabolism due to the intrinsic antibacterial activity of elemental sulfur and catalytic generation of reactive oxygen species, which exhibit effective therapeutic effect on subcutaneously implanted infection model induced by representative pathogenic Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Plus, the negatively charged surface makes the SQDs have excellent hemocompatibility and low toxicity, which all highlight the critical prospect of the SQDs as a potent biocompatible antibacterial agent in clinical infection therapy.