Broad-spectrum Antibacterial Agents Research Articles

Effects of triclosan on antioxidant- and apoptosis-related genes expression in the gill and ovary of zebrafish.

Triclosan (TCS) is a broad-spectrum antibacterial and anti-fungal agent used in a broad variety of personal care products (PCPs) throughout the world. However, the molecular mechanism of TCS’s effects on the gill and ovary of fish is not clear. In this study, the effects of TCS exposure on expression of antioxidant- and apoptosis-related genes were investigated in the gill and ovary of zebrafish (Danio rerio). Zebrafish were exposed to 0, 17, 34, or 68 µg/l TCS for 42 days. Antioxidant-related genes (SOD, GPx1a, CAT, sMT-B, and MT-2) in the gill were significantly downregulated in the 34 (except GPx1a) and 68 µg/l TCS groups, and these genes (except MT-2) in the ovary were significantly downregulated in the 68 µg/l TCS group. Apoptosis-related gene (Bax and p53) expression level in the gill were significantly downregulated in the 68 µg/l TCS group, while the ratios of BCL-2 to Bax and MDM2 gene were significantly upregulated. The Bax gene in the ovary was significantly upregulated in the 34 and 68 µg/l TCS groups, while the ratio of BCL-2 to Bax was significantly downregulated. Moreover, the p53 gene in the ovary in the 34 µg/l TCS group was significantly upregulated. In addition, the MDA contents in the gill in the 34 and 68 μg/l TCS treated groups and in the ovary in 68 μg/l group were significantly increased. The results showed that the higher dose of TCS might cause oxidative damage in the gills and ovaries and accelerate ROS-dependent ovary apoptosis in zebrafish.

Nitrate Reductase mediated synthesis of surface passivated nanogold as broad-spectrum antibacterial agent

The green synthesis of gold nanoparticles has attracted tremendous interest owing to their unique physicochemical properties and widespread applications which are primarily size-dependent. The stability, less reaction time, and use of biological resources as novel nanofactories as an alternative to conventional synthesis strategies are the main objectives of green synthesis approaches. However, to attain size-controlled synthesis from the biogenic route is still a challenge. Hence, use of nontoxic stabilizers becomes increasingly essential. Herein, we describe an emerging, simple, nonconventional approach to synthesize stable and size-controlled biogenic nanogold using cell lysate supernatant containing nitrate reductase of Bacillus licheniformis in the presence of Tween 20 and dodecanethiol respectively. The face-centered central composite design used for the optimization of gold nanoparticles (AuNPs) biosynthesis. The maximum AuNPs biosynthesis obtained using the optimized media variables, glucose (2.1 g/L), peptone (14.05 g/L), yeast extract (4.14 g/L), and potassium nitrate (3.91 g/L) was 0.769 a.u. Highly stable monodispersed nanogold of 10.4 ± 0.6 nm and 12.5 ± 0.9 nm sizes arranged in ordered self-assembly was obtained. The stability profile and kinetics of bioreduction was evaluated with respect to time, and the involvement of the nitrate reductase enzyme in bioreduction was validated by inhibitor study. The physicochemical properties of biogenic nanoparticles were characterized using multiple spectroscopy and microscopy techniques. The obtained nanogold demonstrated excellent bactericidal property against both gram-negative and gram-positive bacteria in size-dependent manner and thus could find tremendous utility in clinical, biological, and environmental applications as a broad-spectrum antibacterial agent.

Mode of nitric oxide delivery affects antibacterial action.

Nitric oxide (NO) is a broad-spectrum antibacterial agent, making it an attractive alternative to traditional antibiotics for treating infections. To date, a direct comparison of the antibacterial activity of gaseous NO (gNO) versus water-soluble NO-releasing biopolymers has not been reported. In this study, the bactericidal action of NO-releasing chitosan oligosaccharides was compared to gNO treatment against cystic fibrosis-relevant Gram-positive and Gram-negative bacteria. A NO exposure chamber was constructed to enable the dosing of bacteria with gNO at concentrations up to 800 ppm under both aerobic and anaerobic conditions. Bacteria viability, solution properties (i.e., pH, NO concentration), and toxicity to mammalian cells were monitored to ensure a thorough understanding of bactericidal action and reproducibility for each delivery method. The NO-releasing chitosan oligosaccharides required significantly lower NO doses relative to gNO therapy to elicit antibacterial action against Pseudomonas aeruginosa and Staphylococcus aureus under both aerobic and anaerobic conditions. Reduced NO doses required for bacteria eradication using water-soluble NO-releasing chitosan were attributed to the release of NO in solution, removing the need to transfer from gas to liquid phase and the associated long diffusion distances of gNO treatment.

1016. Standardized Antimicrobial Administration Ratio (SAAR) and Clostridioides difficile Infection Standardized Infection Ratio (SIR): Are they connected? An Evaluation of 28 Hospitals

Background Clostridioides difficile infections (CDIs) are the most prevalent healthcare-associated infection in the U.S. Of all CDIs, most are related to healthcare exposures and are potentially preventable by reducing unnecessary antibiotic use and interrupting patient-to-patient transmission of CDI.MethodsThe adult SAARs for 4 antimicrobial agent categories were compared with the CDI SIR at 28 facilities with greater than 100 beds across the health system for the calendar year of 2018. The 4 adult antimicrobial agent categories chosen for comparison were: antibacterial agents posing the highest risk for CDI, broad-spectrum antibacterial agents predominantly used for hospital-onset infections (BSHO), broad-spectrum antibacterial agents predominantly used for community-acquired infections (BSCA) and all antibacterial agents.ResultsThe 2018 aggregate CDI SIR for the 28 facilities was 0.609. The aggregate SAAR for the adult antimicrobial agent categories were 1.05 for the antibacterial agents posing the highest risk for CDI, 1.05 for BSHO, 0.88 for BSCA, and 1.03 for all antibacterial agents. No correlation was seen between any of the 4 adult SAAR antimicrobial agent categories and the facility CDI SIR (Figure 1–4).ConclusionWhile reducing unnecessary antibiotics is an important strategy in preventing CDIs, having a higher observed vs. predicted administration ratio in the four antimicrobial agent categories studied was not correlated with a higher CDI SIR, including the CDI SAAR category. Reduction of CDI is challenging requiring a multipronged approach to include infection control strategies, appropriate testing, and antimicrobial stewardship. Disclosures All authors: No reported disclosures.

1072. The Role of an On-site Infectious Disease Specialist in Hospital-Based Antimicrobial Stewardship Programs

BackgroundAntimicrobial stewardship programs (ASPs) are now a requirement for many hospitals, but a large proportion of US hospitals lack an on-site Infectious Disease (ID) specialist. We sought to compare the processes and outcomes of ASPs at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist.MethodsThis retrospective cohort included all acute-care patients in VHA hospitals admitted during 2016, or 2 years after a VHA mandate for hospital-based ASPs. Data from a mandatory nationwide survey were used to identify hospitals that self-reported the absence of an on-site ID specialist, including an ID physician or ID pharmacist, in 2016. Antimicrobial use was quantified at the hospital-level as days-of-therapy (DOTs) per 1,000 days present and categorized based on National Healthcare Safety Network definitions. A facility-level negative binomial regression model with risk adjustments made for aggregated case-mix and facility-level factors was used to determine the association between the presence of an on-site ID specialist and antimicrobial use.ResultsEighteen of 122 (14.8%) hospitals lacked an on-site ID specialist. Non-ID hospitals had fewer admissions per month than ID sites (mean 107.3 vs. 425.4, P < 0.01). An ASP policy and an ASP pharmacy champion were present at ≥90% of hospitals with and without an ID specialist. Core ASP strategies were frequently used in both ID and non-ID sites, including prior authorization (90.4% vs. 83.3%, P = 0.41) and prospective audit-and-feedback (76.9% vs. 66.7%, P = 0.38). Broad-spectrum antibacterial use (263.9 vs. 317.6 DOTs per 1,000 days-present, P = 0.01) but not total antimicrobial use (600.8 vs. 634.3 DOTs per 1,000 days-present, P = 0.34) was lower at ID vs. non-ID hospitals. After facility-level risk-adjustment, broad-spectrum antibacterial use (OR = 0.81, 95% CI 0.69–0.94) but not total antimicrobial use (OR = 0.92, 95% CI 0.70–1.21) was lower at ID hospitals.ConclusionAn on-site ID specialist was not associated with greater use of core ASP strategies, but the presence of an on-site ID specialist was associated with less frequent prescribing of broad-spectrum antibacterial agents. An on-site ID specialist may be an important part of an effective hospital-based ASP.Disclosures All authors: No reported disclosures.

Cucurbit[7]uril-Anchored Porphyrin-Based Multifunctional Molecular Platform for Photodynamic Antimicrobial and Cancer Therapy

Here we report a photoactive supramolecular assembly that is multifunctional and constructed by covalently linking four receptor molecules (cucurbit[7]uril) to a porphyrin derivative with suitable linkers. While this molecular platform serves very efficiently as a light-triggered broad-spectrum antibacterial agent, owing to its negligible dark cytotoxicity and the presence of host molecules (CB7), it can also be utilized as a vehicle to carry drug molecules for a combined chemo and photodynamic cancer therapy.

Physico-chemical and antibacterial properties of gold nanoparticles synthesized using Avicennia marina seeds extract

This study investigated the synthesis and antibacterial activity of gold nanoparticles (AuNPs), produced using aqueous Avicennia marina seed extract. Reaction of the extract with chloroauric acid led to the reduction of auric chloride and the formation of AuNPs within 10 min at 28 °C. The size, shape and elemental composition of the nanoparticles (NPs) was studied using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and UV-visible spectroscopy. Furthermore, the biological capping agents of the NPs were identified via Fourier-transform infrared spectroscopy (FT-IR). The seed extract served as an effective bio-reductant for the synthesis of AuNPs. High-resolution TEM images revealed the NPs to be predominantly spherical in shape, with some hexagonal and rod-shaped particles observed. The AuNPs displayed inhibitory activity against a range of human pathogenic bacterial species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. Complete inhibition was observed at 200 µg/mL. However, E. faecalis was resistant to the NPs. The results suggest that AuNPs synthesised using aqueous seed extracts of mangrove species such as A. marina may serve as broad-spectrum antibacterial agents, particularly for antibiotic resistant strains.

Spotting sporotrichosis skin infection: The first Australian paediatric case series.

Sporotrichosis is a dermatomycosis caused by the dimorphic fungus, Sporothrix schenckii, with various outbreaks across Australia attributed to mouldy hay. Our objective was to investigate the clinical presentation and management of cutaneous sporotrichosis in a paediatric population of Western Australia. A retrospective case review was performed for S. schenckii infections in children below 18 years, between January 2000 and November 2017. Cases were identified from the state-wide laboratory database and additional clinical data obtained from medical records. Thirty-two cases of microbiologically proven S. schenckii infection were identified, mostly from rural areas (n = 20, 63%). Complete clinical data were available for 11 cases (34%). The most common risk factors were exposure to farm animals and hay, arthropod bites and outdoor activities. The median duration from symptom onset to correct diagnosis was 6 weeks (interquartile range: 4-7 weeks). Most cases were initially treated with multiple, broad-spectrum antibacterial agents (n = 7, 64%). Targeted therapy (itraconazole) was used in all cases once the diagnosis was made, with a median treatment duration of 5 months (interquartile range: 4-6 months). Morbidity included scarring (n = 4, 31%), itraconazole associated diarrhoea (n = 1, 8%) and mild hepatotoxicity (n = 1, 8%). Summarising the clinical experience of these cases is a useful guide for clinical recognition and may serve to shorten the interval between onset and diagnosis, and avoid the need for antibacterial therapy. These data highlight the importance of recognising Sporotrichosis in children outside an outbreak setting, leading to timely diagnosis and appropriate treatment with antifungal agents.

Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework-Based Drug Delivery Systems.

Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology-related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH-responsive zeolitic imidazolate framework-8-polyacrylic acid (ZIF-8-PAA) material is constructed for bacterial infection-targeted delivery of ammonium methylbenzene blue (MB), a broad-spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB-loaded ZIF-8-PAA nanoparticles are modified with AgNO3 /dopamine for in situ reduction of AgNO3 to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH2 -polyethylene glycol (Van/NH2 -PEG), leading to the formation of a composite nanomaterial, ZIF-8-PAA-MB@AgNPs@Van-PEG. Dynamic light scattering, transmission electron microscopy, and UV-vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.

Effects of sulfanilamide on boar sperm quality, bacterial composition, and fertility during liquid storage at 17°C.

Sulfanilamide (SA) is an effective broad-spectrum antibacterial agent in human and veterinary medicine. The purpose of this study was to evaluate the effects of SA on boar sperm quality during liquid storage at 17°C and determine the optimal concentration of SA and its effects on bacterial growth, microbial composition, and maternal fertility. Boar ejaculates were diluted with a basic extender, containing different concentrations of SA, and stored in a 17°C incubator for 6days. The sperm motility, plasma membrane integrity, and acrosome integrity were measured daily. The results showed that when the concentration of SA was 0.02g/L, the sperm quality parameters were significantly higher than those of all other treatment groups (p<.05). We also monitored the bacterial growth and compared the differences in the microbial species between the 0.02g/L SA group and the control by 16S rDNA sequencing. The results revealed that some bacteria, such as Staphylococcus and Pseudomonas, were considerably lower in the 0.02g/L SA group than in the control group (p<.05). In addition, preserved semen was used for artificial insemination, and results showed that 0.02g/L SA group had a higher litter size, and its pregnancy rate was 92.5%.

MoS2-Modified Curcumin Nanostructures: The Novel Theranostic Hybrid Having Potent Antibacterial and Antibiofilm Activities against Multidrug-Resistant Hypervirulent Klebsiella pneumoniae.

The recent emergence of hypervirulent clinical variants of Klebsiella pneumoniae (hvKP) causing community-acquired, invasive, metastatic, life-threatening infections of lungs, pleura, prostate, bones, joints, kidneys, spleen, muscles, soft-tissues, skin, eyes, central nervous system (CNS) including extrahepatic abscesses, and primary bacteremia even in healthy individuals has posed stern challenges before the existing treatment modalities. There is therefore an urgent need to look for specific and effective therapeutic alternatives against the said bacterial infection or recurrence. A new type of MoS2-modified curcumin nanostructure has been developed and evaluated as a potential alternative for the treatment of multidrug-resistant isolates. The curcumin quantum particles have been fabricated with MoS2 via a seed-mediated hydrothermal method, and the resulting MoS2-modified curcumin nanostructures (MQCs) have been subsequently tested for their antibacterial and antibiofilm properties against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. In the present study, we found MQCs inhibiting the bacterial growth at a minimal concentration of 0.0156 μg/mL, while complete inhibition of bacterial growth was evinced at concentration 0.125 μg/mL. Besides, we also investigated their biocompatibility both in vitro and in vivo. MQCs were found to be nontoxic to the SiHa cells at a dose as high as 1024 μg/mL on the basis of the tested adhesion, spreading of the cells, and also on the various serological, biochemical, and histological investigations of the vital organs and blood of the Charles Foster Rat. These results suggest that MQCs have potent antimicrobial activities against hvKP and other drug resistant isolates and therefore may be used as broad spectrum antibacterial and antibiofilm agents.

Abstract 3857: Discovery and structure-activity relationship studies of TP-2846: a novel tetracycline antileukemia agent

Abstract Tetracyclines are broad-spectrum antibacterial agents. They inhibit bacterial protein synthesis by binding to the 30S subunit of the bacterial ribosome. Besides tetracyclines’ potent antibacterial activity, there is accumulating in vitro and in vivo evidence that tetracycline derivatives, including COL-3, doxycycline, minocycline, and tigecycline (Škrtić, Cancer Cell (2011) 20(5): 10.015), also possess anticancer properties against both liquid and solid tumors. Several tetracyclines have been investigated in various cancer clinical trials. However, most of these human trials, including the recent phase 1 study of tigecycline in patients with acute myeloid leukemia (AML) (Reed, Cancer Med (2016) 5(11): cam4.845), have yielded disappointing results. We believe that the failure of tigecycline in the AML trial is due to its inadequate in vitro potency (single-to-double digits µM range). To identify more potent anticancer tetracyclines, we explored the anticancer, particularly antileukemia activities of novel tetracycline analogs created by the proprietary tetracycline total synthesis platform during our antibacterial drug discovery efforts. A collection of 2368 novel, structurally diverse tetracycline analogs was screened against the leukemia cell line THP-1 in an HTS format (386-well). From the 68 hits (2.9% hit rate) with sub-µM antiproliferation activity, five lead compounds derived from two sub-series were selected for further profiling, including TP-2846, which displayed one of the lowest GI50 values at 0.75 µM. As a comparison, tigecycline had a GI50 of 29 µM in the same assay. The five lead compounds were subsequently evaluated for antiproliferation activity in other liquid and solid tumor lines, including MV4-11 (0.020 µM), MOLT-4 (0.09 µM), K-562 (0.43 µM), HL-60 (0.37 µM), CCRF-CEM (0.067 µM), KG-1 (0.27 µM), Kasumi-1 (0.16 µM), U-87 (0.09 µM), HepG2 (1.6 µM), CCL-247 (0.26 µM), CCL-222 (0.48 µM), HTB-77 (0.26 µM), and CRL-1923 (6.2 µM) (values in parentheses are GI50 of TP-2846). TP-2846 and another lead compound were also screened against the NCI60 panels. TP-2846 demonstrated the highest overall antiproliferation potency against most cell lines tested and is 10-50 folds more potent than tigecycline. Using MV4-11 as the primary screening cell line, we subsequently evaluated and studied the structure-activity relationships of more than 170 analogs of TP-2846 with systematic variations at the C4, C7, and C8 positions of the tetracycline core. Although a number of new analogs displayed comparable antiproliferation activity in MV4-11, TP-2846 remains the most potent analog overall in vitro and was selected to be further profiled in vitro and in vivo (see accompanying abstracts “In vitro characterization of TP-2846: a novel tetracycline antileukemia agent” and “In vivo activities of TP-2846: a novel tetracycline antileukemia agent”). Citation Format: Cuixiang Sun, Peng Zhao, Diana Hunt, Kathryn Kerstein, Joseph Newman, Sara McKellip, Robert Bostwick, Jacques Dumas, Xiao-Yi Xiao. Discovery and structure-activity relationship studies of TP-2846: a novel tetracycline antileukemia agent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3857.

Phytochemicals and Antibacterial Activity of Leaf and Stem Extracts of Ageratum conyzoides (Linn) on Some Clinical Isolates

Phytochemicals and antibacterial activity of leaf and stem extracts of Ageratum conyzoides on four clinical isolates, Staphylococcus aureus, Salmonella typhi, Escherichia coli and Pseudomonas areuginosa were investigated. Filtrates from ethanol extract of each of the powdered samples of the leaves and stem of A. conyzoides were evaporated to thick residues. 1 g each of these residues was dissolved in 5 ml of distilled water followed by double dilution to obtain concentrations of 200, 100, 50, 25, 12.5 and 6.25 mg/ml. Ciprofloxacin and distilled water were used as positive and negative controls, respectively. Antibacterial activity was assayed using Agar-well diffusion technique while the MIC was determined from the curve of square of radius diameter of inhibition against log concentration of the extract. Results showed that the leaf and stem of A. conyzoides contain comparable amounts of the phytochemicals with higher contents of flavonoid (0.97-0.98 %), saponin (0.97-0.98 %), and alkaloids (0.90 %) than tannin (0.187-0.188 %) and phenol (0.022 %). The extracts of A. conyzoides showed concentration-dependent activity against all the test bacterial isolates. The test organisms were found to be susceptible to the extracts at concentration of ? 50 mg/ml except S. typhi and P. aeruginosa that were susceptible to the stem extract at ?25 and ?100 mg/ml, respectively, whereas, for ciprofloxacin, some were susceptible even at very low concentration of 6.25 mg/ml. The MIC values were in the range of 69.18-75.86 mg/ml, 36.3-144.54 mg/ml and 7.59-38.0 mg/ml for the leaves and stem extracts and ciprofloxacin, respectively. The extracts could therefore be used as a broad spectrum antibacterial agent.

In vitro bactericidal activity of levonadifloxacin (WCK 771) against methicillin- and quinolone-resistant Staphylococcus aureus biofilms.

Staphylococcus aureus causes a wide range of infections, such as endocarditis, pneumonia, osteomyelitis, skin and soft tissue infections, and implant/in-dwelling device-related infections. S. aureus poses a significant challenge to clinicians because of its ability to rapidly acquire multi-drug resistance and quickly progress into a recurrent, chronic infection by biofilm formation. Levonadifloxacin (WCK 771) is a novel broad-spectrum antibacterial agent (it recently completed a phase 3 trial in India) with a differentiated mechanism of action involving high affinity to staphylococcal DNA gyrase, and is active against multi-drug-resistant (MDR) S. aureus, including those that are resistant to quinolones. The present study investigated the bactericidal activity of levonadifloxacin against biofilm-embedded S. aureus clinical isolates in comparison with other anti-S. aureus drugs. The bactericidal activity of levonadifloxacin and comparator drugs such as vancomycin, linezolid and daptomycin was evaluated against planktonic and biofilm-encapsulated recent methicillin- and quinolone-resistant S. aureus clinical isolates using time-kill, biofilm eradication and scanning electron microscopy analysis. Levonadifloxacin displayed a consistent ≥90 % bacterial kill rate against biofilm-embedded organisms, while vancomycin and linezolid displayed variable activity and daptomycin did not show any activity. Scanning electron microscopy images further confirmed the efficacy of levonadifloxacin against biofilm, showing the disruption of biofilm structure and a corresponding reduction in the viable bacterial count. These results show that levonadifloxacin has an improved bactericidal effect on biofilm-embedded quinolone-resistant S. aureus and meticillin-resistant S. aureus, and that it can be a promising treatment option for such infections.

A Case Report on Disseminated Candida Lusitaniae Infection and Tuberculous Lymphadenitis in Patient with Compound Heterozygous Pair of Mutations of CYBA Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is an unusual hereditary chief immune- deficiency disease, which is characterized by nicotinamide adenine dinucleotide phosphate oxidase (NADPH) system malfunction. In this type of disease the phagocytic cells could not be able to destroy the pathogens at the time of development of an infection. This will result in patient's susceptibility to recurrent and intractable microbial infections. The disease is considered to be a genetically heterogeneous having equal susceptibility among all the ethnic groups. Patients with (CGD) suffer from persistent, fatal fungal and bacterial infections of the skin, the lymph nodes, airways, brain, liver, and bones. Whenever there is an infection with any odd microorganisms the susceptibility for CGD rises. In our article we aim to report a case study of a 4 months old female with disseminated candidiasis Tuberculosis lymphadenitis in details. The infant was treated successfully with antifungal voriconazole and broad spectrum antibacterial agents as well as anti-mycobacterial medications. When the patient was followed up later, it showed regression of the abnormal reports. But later developed CNS Candida and disseminated tuberculous with sequalae. Diagnosis was confirmed as heterozygous CYBA for p22phox, defect by genetic analysis. P22phox is an omnipresent protein which is coded by the gene CYBA located on the long arm of chromosome16. P22phox it is crucial factor of the enzyme superoxide-generating (NADPH) oxidase. Infection with bacteria, Candida lusitaniae is maximum among the patients who are suffering with haematological malignancies. The chance of the infection rises when the patient is receiving chemotherapy. This type of infection usually occurs among the patients who are presenting fungal infection that has already spread throughout the blood and among them only 7.3% of the patients are showing the symptomatic manifestations of peritonitis. However, the most difficult point is that the laboratory culture is not the answer for the growth of the particular microorganisms as these organisms are extremely difficult to culture or separate.

Polyethyleneimine and quaternized ammonium polyethyleneimine: the versatile materials for combating bacteria and biofilms

Bacterial infection has become a serious clinical concern due to the emergence of drug-resistance and biofilm formation. Therefore, it is in great demand to develop efficient antimicrobial agents to treat bacterial infection without using antibiotics. Herein, we successfully prepared four quaternized ammonium PEI (QPEI: PEI1200-C2, PEI1200-C4, PEI1200-C6 and PEI1200-C8) using the commercial available PEI1200. Both PEI and four QPEI presented broad-spectrum antimicrobial activity against Gram-negative bacteria (E. coli, and P. aeruginosa) and Gram-positive bacteria (B. amyloliquefaciens and S. aureus), especially PEI1200-C6 showed the strongest antimicrobial activity with good biocompatibility at the MIC concentrations. Besides, PEI1200-C6 showed 4-16-fold better antibacterial effect than PEI1200, and fluorescent microscope imaging demonstrated that both of them could efficiently eradicate biofilms formed by four bacterial strains in vitro. As the accessible broad-spectrum antibacterial agents, PEI1200 and PEI1200-C6 are significant candidates to treat bacterial infections or eradicate biofilms on indwelling medical devices.

Ligands and Receptors with Broad Binding Capabilities Have Common Structural Characteristics: An Antibiotic Design Perspective.

The spread of antibiotic resistance is one of the most serious global public-health problems. Here we show that a particular class of homomers with binding sites spanning multiple protein chains is particularly suitable for targeting by broad-spectrum antibacterial agents because due to the slow evolutionary change of such binding pockets, ligands of such homomers are much more likely to bind their homologs than ligands of monomers, or homomers with a single-chain binding site. Additionally, using de novo ligand design and deep learning, we show that the chemical compounds that can bind several different receptors have common structural characteristics and that halogens and fragments similar to the building blocks existing antimicrobials are overrepresented in them. Finally, we show that binding multiple receptors selects for flexible compounds, which are less likely to accumulate in Gram-negative bacteria; thus there is trade-off between reducing the emergence of resistance by multitargeting and broad-spectrum antibacterial activity.

Isolation and Detection of Bacteriocin-Like Inhibitory Substances-Producing Bacteria from Fermented Mare’s Milk Sumbawa

Bacteriocin-like inhibitory substances (BLIS) produced by bacteria is a promising future food preservative agent. This study aimed to obtain bacterial strains that can produce broad-spectrum antibacterial agents and identify the best BLIS producer species based on 16S rDNA sequences. The bacterial strains were isolated from fer-mented mare’s milk using MRS and M17 agar medium. The isolates then were initially screened based on its antibacterial activity of crude cells against Staphylococcus aureus ATCC 6538. The selected strains were cultured and harvested for its cell-free supernatant (CFS). The pH of CFS was adjusted to 6.5 then used for antibacterial activity as-says against ten pathogenic bacteria. Also, the proteinaceous nature of BLIS compound was confirmed by testing with proteinase K. The gDNA of selected isolates was extracted and the 16S rDNA was am-plified using the polymerase chain reaction method then sequenced. The 16S rDNA sequences of the selected strains were used to identify the species using BLAST nucleotides from NCBI then the phylogenetic trees were constructed. 32 isolates was obtained, but only three iso-lates (BC9, SB7, and DC12) were selected as a result of antibacterial screening for further assays. The neutralized-CFS (N-CFS) of these isolates exhibited broad-spectrum antibacterial activity. The N-CFS could be assumed as BLIS. The isolate of BC9 was identified as Ba-cillus amyloliquefaciens strain BC9 that has 99.99 % similarity with B. amyloliquefaciens KC-1, SB7 was Lactobacillus plantarum strain SB7 that has 99.99 % similarity with Lb. plantarum JMC 1149T, and DC12 was Lactobacillus rhamnosus strain DC12 that has 100 % sim-ilarity with Lb. rhamnosus DSM 20021T. Thus, the BLIS produced by those strains is potential for future food and beverages preservations.

Precise management of chronic wound by nisin with antibacterial selectivity

Traditional broad-spectrum antibacterial agents are limited by high toxicity and the destruction to the bacterial flora balance in the wound site. Herein, we propose an opinion that one or several especial antibacterial peptides are adopted to kill the target bacteria in order to precisely manage the bacteria infected chronic wound under the premise of biobalance, and specially employ nisin to treat S. aureus infected chronic wound as model with positive effects. The results showed that without cytotoxicity to the normal cells, only 25 ppm nisin could contrapuntally kill S. aureus and have little inhibitory to other bacteria. Mechanism of antibacterial selectivity indicated the superior biomolecular interaction between nisin and S. aureus compared with E. coli and normal cells. Furthermore, nisin significantly accelerated the healing process of S. aureus-infected rabbit full thickness burn wound, but had no effect on the E. coli-infected wound as a comparison. Therefore, it has been demonstrated that special peptides with antibacterial selectivity can be adopted to precise management for bacteria infected chronic wound under good biobalance.

Synthesis and evaluation of Quinoline-3-carbonitrile derivatives as potential antibacterial agents

New quinoline-3-carbonitrile derivatives were synthesized and evaluated for their potential antibacterial behavior. Compounds were obtained by a one-pot multicomponent reaction of appropriate aldehyde, ethyl cyanoacetate, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one and ammonium acetate. Structures were established by different physical and spectroscopic techniques. The molecular geometry, vibration frequencies, HOMO–LUMO energy gap, molecular hardness (g), ionization energy (IE), electron affinity (EA), and total energy of these compounds was assessed by DFT studies, employing DFT/RB3LYP method. Preliminary antibacterial studies using both Gram-positive and Gram-negative bacterial strains and cytotoxicity studies on mammalian cells revealed their promising antibacterial activity, without causing any severe host toxicity. All the compounds (QD1-QD5) in this study obeyed the ‘Lipinski’s Rule of Five’ with logP values <5 and HBA <10, hydrogen bond donor’s <5. The most active compound QD4 showed good interaction with the target DNA gyrase; target enzyme for quinoline class of antibiotics, which reveals its probable mechanism of action. Results of all these studies establish these compounds as important scaffolds with broad-spectrum antibacterial activity with no off-target toxicity. Having lower band gap energy of 3.40 eV and a low lying LUMO for compound QD4, this compound may be a valuable starting point for the development of quinoline-3-carbonitrile based broad-spectrum antibacterial agents.