Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin.

Rifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 µg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the combinations of 3c with the major anti-TB drugs are antagonistic. Consistent with RIF, compound 3c induced large amounts of reactive oxygen radicals (ROS) in the cells of Mtb. The killing kinetics of compound 3c and RIF are very similar. Furthermore, molecular docking showed that compound 3c was able to access the RIF binding pocket of the ß subunit of Mtb RNA polymerase (RNAP). Experiments in mice showed that compound 3c increased the variety of intestinal flora in mice, while RIF significantly decreased the diversity of intestinal flora in mice. In addition, compound 3c is non-toxic to animal cells with a selection index (SI) much more than 10. The evidence from this study suggests that the further development of 3c could contribute to the development of novel drug for TB treatment.

Endophytic Streptomyces sp. NEAU-DD186 from Moss with Broad-Spectrum Antimicrobial Activity: Biocontrol Potential Against Soilborne Diseases and Bioactive Components.

Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum. To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 108 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC50 of 2.46 and 2.58 µg ml-1) and B. sorokiniana (EC50 of 3.92 and 3.95 µg ml-1). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases.

Molecular Engineering of Laser-Induced Graphene for Potential-Driven Broad-Spectrum Antimicrobial and Antiviral Applications.

Worldwide, countless deaths have been caused by the coronavirus disease 2019. In addition to the virus variants, an increasing number of fatal fungal infections have been reported, which further exacerbates the scenario. Therefore, the development of porous surfaces with both antiviral and antimicrobial capacities is of urgent need. Here, a cost-effective, nontoxic, and metal-free strategy is reported for the surface engineering of laser-induced graphene (LIG). The authors covalently engineer the surface potential of the LIG from -14 to ≈+35 mV (LIG+ ), enabling both high-efficiency antimicrobial and antiviral performance under mild conditions. Specifically, several candidate microorganisms of different types, including Escherichia coli, Streptomyces tenebrarius, and Candida albicans, are almost completely inactivated after 10-min solar irradiation. LIG+ also exhibits a strong antiviral effect against human coronaviruses: 99% HCoV-OC43 and 100% HCoV-229E inactivation are achieved after 20-min treatment. Such enhancement may also be observed against other types of pathogens that are heat-sensitive and oppositely charged. Besides, the covalent modification strategy alleviates the leaching problem, and the low cytotoxicity of LIG+ makes it advantageous. This study highlights the synergy of surface potential and photothermal effect in the inactivation of pathogens and it provides a direction for designing porous materials for airborne disease removal and water disinfection.

Study on the mechanism of ROS-induced oxidative stress injury and the broad-spectrum antimicrobial performance of nickel ion-doped V6O13 powder.

In this study, pure V6O13 and nickel ion-doped V6O13 powders were synthesized by a simple hydrothermal-calcination method, and their broad-spectrum antimicrobial properties and mechanisms were investigated. The crystal structure, morphology, and chemical state of the powders were thoroughly analyzed by XRD, SEM, TEM, XPS, and UV-Vis. Their antimicrobial properties and mechanisms were evaluated by the ring of inhibition, bio-SEM, live-dead cell staining, ROS detection, and protein leakage experiments. The results showed that nickel ion doping modulated the oxygen defects of V6O13, generating more reactive oxygen species and leading to more severe oxidative stress, resulting in a broad-spectrum and highly efficient antimicrobial effect. This study also revealed the antimicrobial mechanism based on oxygen defect -induced ROS production, which caused cellular oxidative stress damage, leading to leakage of intracellular substances and cell death. This study not only demonstrates the potential of V6O13 as an efficient antimicrobial agent but also provides a strong experimental basis and theoretical support for the engineering design and optimization of novel antimicrobial materials by modulating material defects through ion doping.

Integrating rapid pathogen identification and antimicrobial susceptibility testing through multiplex TaqMan qPCR assay.

Timely bacterial identification (ID) and antimicrobial susceptibility testing (AST) are of significance for therapy of bacteria-infected patients. In the present study, we developed a multiplex TaqMan qPCR assay for rapid and accurate ID and AST of three common hospital acquired pneumonia species, namely Acinetobacter baumannii, Klebsiella pneumoniae and Staphylococcus aureus. In this assay, DNA extraction and bacterial co-incubation with antibiotics are accomplished based on a common PCR instrument. ID of three bacteria is based on specific conserved DNA sequence fragment (gltA for A. baumannii, phoE for K. pneumoniae and nuc for S. aureus) detection through multiplex TaqMan qPCR assay within 80 min. AST of three bacteria could be acquired within 200 min based on genomic DNA fold change detection after 2 h of antibiotic exposure. Testing of 23 bronchoalveolar lavage fluid samples spiked by different A. baumannii isolates, 20 bronchoalveolar lavage fluid samples spiked by different K. pneumoniae isolates, and 14 bronchoalveolar lavage fluid samples spiked by different S. aureus isolates showed that the multiplex TaqMan qPCR assay had 100% (95% CI: 85.69-100), 100% (95% CI: 83.89-100) and 100% (95% CI:78.47-100) identification agreement with the initial spiked bacteria. Subsequent AST results compared with the standard broth microdilution method showed an overall agreement of 91.30% (95% CI: 73.20 to 97.58) for A. baumannii, 90% (95% CI: 69.90 to 97.21) for K. pneumoniae and 92.86% (95% CI: 68.53 to 98.73) for S. aureus based on the current multiplex TaqMan assay. Due to the high rapidity, good agreement, simplicity, and high throughput, this multiplex TaqMan assay could be helpful for ID and broad-spectrum AST in A. baumannii, K. pneumoniae and S. aureus, as well as potentially applicable for other clinical bacteria by changing the primers and probes.

Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer.

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. STATEMENT OF SIGNIFICANCE: Healing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

Endophytic Streptomyces sp. NEAU-ZSY13 from the leaf of Perilla frutescens, as a promising broad-spectrum biocontrol agent against soil-borne diseases.

Soil-borne diseases cause significant economic losses in global agricultural production. These diseases are challenging to control due to the invasion of multiple pathogens into host plants, and traditional chemical control methods often yield unsatisfactory results. In this study, we isolated and identified an endophytic Streptomyces, designated as NEAU-ZSY13, from the leaf of Perilla frutescens. This isolate exhibited broad-spectrum antifungal activity against 17 soil-borne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. Additionally, it displayed strong antibacterial activity against the soil-borne phytopathogenic bacterium Ralstonia solanacearum. To assess its biocontrol potential, the isolate was utilized to produce a biofertilizer through solid-state fermentation. The fermentation conditions were optimized using response surface methodology to maximize the spore production. The results revealed that more abundant spores were produced with a 1:2 ratio of vermicompost to wheat bran, 60% water content, 20% inoculation amount and 28°C. Subsequent pot experiments demonstrated that the application of the biofertilizer with a spore concentration of 108 CFU/g soil effectively suppressed the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, with biocontrol efficacies of 72.2 and 78.3%, respectively. Chemical analysis of NEAU-ZSY13 extracts, using nuclear magnetic resonance spectrometry and mass analysis, identified niphimycin C and niphimycin A as the primary active constituents. These compounds exhibited high activity against R. solanacearum (EC50 of 3.6 and 2.4 µg mL-1) and B. sorokiniana (EC50 of 3.9 and 3.4 µg mL-1). In conclusion, this study demonstrates the potential of Streptomyces sp. NEAU-ZSY13 as a biofertilizer for the control of soil-borne diseases.

Impact of nasal photodisinfection on SARS-CoV-2 infection in an industrial workplace.

Objectives: We aimed to evaluate a quality improvement initiative designed to control SARS-CoV-2 (COVID) using the large-scale deployment of antimicrobial photodisinfection therapy (aPDT) for nasal decolonization in a Canadian industrial workplace (a food processing plant). Study design: Using a retrospective chart review of treatment questionnaires, linked to COVID laboratory testing results, a quality improvement assessment was analyzed to determine treatment effectiveness and safety. Methods: This voluntary aPDT intervention involved the administration of a light-sensitive liquid to the nose followed by nonthermal red-light irradiation on a weekly basis. Employees in food processing industries are at increased risk for COVID infection due to the nature of their work environments. In an effort to mitigate the transmission and consequences of the disease among such workers and the community at large, aPDT was added to a well-established bundle of pre-existing pandemic safety measures (e.g., mask-wearing, testing, contact tracing, workplace-engineered barriers, increased paid sick leave). Results: From December 2020 to May 2021, we found high interest in and compliance with aPDT treatment, along with a statistically significant lower PCR test positivity rate in the study population in comparison to the case rates for the local Canadian province. Treatment safety monitoring and outcomes of the aPDT program demonstrated no serious adverse events. Conclusions: This study suggests nasal photodisinfection provides safe and effective COVID viral suppression when deployed across the majority of workers in an industrial workplace setting.

Broad-Spectrum Antimicrobial Action of Cell-Free Culture Extracts and Volatile Organic Compounds Produced by Endophytic Fungi Curvularia Eragrostidis.

Endophytes are the mutualistic microorganisms that reside within the host plant and promote plant growth in adverse conditions. Plants and their endophytes are engaged in a symbiotic relationship that enables endophytes to access bioactive genes of the ethnomedicinal plants, and, as a result, endophytes are constantly addressed in the sector of pharmaceuticals and agriculture for their multidomain bio-utility. The gradual increase of antimicrobial resistance can be effectively countered by the endophytic metabolites. In these circumstances, in the present investigation, endophytic Curvularia eragrostidis HelS1 was isolated from an ethnomedicinally valuable plant Helecteris isora from East India's forests. The secondary volatile and non-volatile metabolites are extracted from HelS1 and are found to be effective broad-spectrum antimicrobials. A total of 26 secondary metabolites (9 volatiles and 17 non-volatiles) are extracted from the isolate, which exhibits effective antibacterial [against six Gram-positive and seven Gram-negative pathogens with a minimum inhibitory concentrations (MIC) value ranging from 12.5 to 400 µg ml-1] and antifungal (against seven fungal plant pathogens) activity. The secondary metabolite production was optimised by one variable at a time technique coupled with the response surface methodology. The results revealed that there was a 34% increase in antibacterial activity in parameters with 6.87 g L-1 of fructose (as a carbon source), 3.79 g L-1 of peptone (as a nitrogen source), pH 6.75, and an inoculation period of 191.5 h for fermentation. The volatile metabolite production was also found to be optimum when the medium was supplemented with yeast extract and urea (0.2 g L-1) along with dextrose (40 g L-1). Amongst extracted volatile metabolites, 1-H-indene 1 methanol acetate, tetroquinone, N, N-diphenyl-2-nitro-thio benzamide, Trans 1, 2-diethyl-trans-2-decalinol, naphthalene, and azulene are found to be the most effective. Our investigation opens up opportunities in the sector of sustainable agriculture as well as the discovery of novel antimicrobials against dreadful phyto and human pathogens.

Exploring Physicians' Views, Perceptions and Experiences about Broad-Spectrum Antimicrobial Prescribing in a Tertiary Care Hospital Riyadh, Saudi Arabia: A Qualitative Approach.

Antimicrobial resistance (AMR) is a global public health threat associated with increased mortality, morbidity and costs. Inappropriate antimicrobial prescribing, particularly of broad-spectrums antimicrobials (BSAs), is considered a major factor behind growing AMR. The aim of this study was to explore physician perception and views about BSAs and factors that impact upon their BSAs prescribing decisions. Qualitative semistructured telephone interviews over an eleven-week period were conducted with physicians in a single tertiary care hospital in Riyadh, Saudi Arabia. Purposeful and snowball sampling techniques were adopted as sampling strategy. All interviews were audio recorded, transcribed verbatim, uploaded to NVivo® software and analysed following thematic analysis approach. Four major themes emerged: views on BSAs, factors influencing BSA prescribing and antimicrobial stewardship: practices and barriers and recommendations to improve appropriate BSA prescribing. Recommendations for the future include improving clinical knowledge, feedback on prescribing, multidisciplinary team decision-making and local guideline implementation. Identification of views and determinants of BSA prescribing can guide the design of a multifaceted intervention to support physicians and policymakers to improve antimicrobial prescribing practices.

Antimicrobial Effects of Equine Platelet Lysate.

The development of antimicrobial resistant bacteria and the lack of novel antibiotic strategies to combat those bacteria is an ever-present problem in both veterinary and human medicine. The goal of this study is to evaluate platelet lysate (PL) as a biological alternative antimicrobial product. Platelet lysate is an acellular platelet-derived product rich in growth factors and cytokines that is manufactured via plateletpheresis and pooled from donor horses. In the current study, we sought to define the antimicrobial properties of PL on select gram-positive and gram-negative bacteria. Results from an end-point in vitro assay showed that PL did not support bacterial growth, and in fact significantly reduced bacterial content compared to normal growth media. An in vitro assay was then utilized to further determine the effects on bacterial growth dynamics and showed that all strains exhibited a slower growth rate and lower yield in the presence of PL. The specific effects of PL were unique for each bacterial strain: E. coli and P. aeruginosa growth was affected in a concentration-dependent manner, such that higher amounts of PL had a greater effect, while this was not true for S. aureus or E. faecalis. Furthermore, the onset of exponential growth was delayed for E. coli and P. aeruginosa in the presence of PL, which has significant clinical implications for developing a dosing schedule. In conclusion, our findings demonstrate the potential value of PL as a broad-spectrum antimicrobial that would offer an alternative to traditional antibiotics for the treatment of bacterial infection in equine species.

Conjugated Polymer and Triphenylamine Derivative Codoped Nanoparticles for Photothermal and Photodynamic Antimicrobial Therapy.

The photothermal conjugated polymer (DPPT-TT) and a triphenylamine derivative (DPATP-CN) codoped nanoparticles (DDNPs) were designed and prepared via self-assembly. The obtained DDNPs exhibit both efficient and stable photothermal properties and excellent ROS production capability to synergistically achieve photothermal therapy (PTT) and photodynamic therapy (PDT). DDNPs showed antimicrobial activity with more than 70%, 90%, and 99% inhibition ratio, respectively, toward Gram-(-) bacteria (E. coli), Gram-(+) bacteria (S. aureus), and fungi (C. albicans) under combined irradiation of near-infrared light and white light. Therefore, DDNPs are broad-spectrum antimicrobial materials and provide a significant perspective to select an appropriate sterilization strategy for different microorganisms.

A marine sulfate-reducing bacterium producing multiple antibiotics: biological and chemical investigation.

A marine sulfate-reducing bacterium SRB-22 was isolated by means of the agar shake dilution method and identified as Desulfovibrio desulfuricans by morphological, physiological and biochemical characteristics and 16S rDNA analysis. In the bioassay, its extract showed broad-spectrum antimicrobial activity using the paper disc agar diffusion method. This isolate showed a different antimicrobial profile than either ampicillin or nystatin and was found to produce at least eight antimicrobial components by bioautography. Suitable fermentation conditions for production of the active constituents were determined to be 28 day cultivation at 25 degrees C to 30 degrees C with a 10% inoculation ratio. Under these conditions, the SRB-22 was fermented, extracted and chemically investigated. So far an antimicrobial compound, mono-n-butyl phthalate, and an inactive compound, thymine, have been isolated and characterized.

Antimicrobial polymers as therapeutics for treatment of multidrug-resistant Klebsiella pneumoniae lung infection.

Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens in hospital-acquired infections. It is often resistant to multiple antibiotics (including carbapenems), and can cause severe pneumonia. In search of effective antimicrobials, we recently developed polyionenes that were demonstrated to be potent against a broad-spectrum of microbes in vitro. In this study, polyionenes containing rigid amide bonds were synthesized to treat multidrug-resistant (MDR) K. pneumoniae lung infection. The polyionene exhibited broad-spectrum activity against clinically-isolated MDR bacteria with low minimum inhibitory concentrations (MICs). It also demonstrated stronger antimicrobial activity against 20 clinical strains of K. pneumoniae and more rapid killing kinetics than imipenem and other commonly used antibiotics. Multiple treatments with imipenem and gentamycin led to drug resistance in K. pneumoniae, while repeated use of the polymer did not cause resistance development due to its membrane-disruption antimicrobial mechanism. Additionally, the polymer showed potent anti-biofilm activity. In a MDR K. pneumoniae lung infection mouse model, the polymer demonstrated lower effective dose than imipenem with negligible systemic toxicity. The polymer treatment significantly alleviated lung injury, markedly reduced K. pneumoniae counts in the blood and major organs, and decreased mortality. Given its potent in vivo antimicrobial activity, negligible toxicity and ability of mitigating resistance development, the polyionene may be used to treat MDR K. pneumoniae lung infection. STATEMENT OF SIGNIFICANCE: Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens in hospital-acquired infections, is often resistant to multiple antibiotics including carbapenems and can cause severe pneumonia. In this study, we report synthesis of antimicrobial polymers (polyionenes) and their use as antimicrobial agents for treatment of K. pneumoniae-caused pneumonia. The polymers have broad spectrum antibacterial activity against clinically isolated MDR bacteria, and eliminate MDR K. pneumoniae more effectively and rapidly than clinically used antibiotics. The polymer treatment also provides higher survival rate and faster bacterial removal from the major organs and the blood than the antibiotics. Repeated use of the polymer does not lead to resistance development. More importantly, at the therapeutic dose, the polymer treatment does not cause acute toxicity. Given its in vivo efficacy and negligible toxicity, the polymer is a promising candidate for the treatment of MDR K. pneumoniae-caused pneumonia.

Post-Obstructive Pneumonia in Patients with Cancer: A Review.

Published literature on post-obstructive pneumonia is difficult to find and consists mainly of case reports or small case series. This entity is encountered most often in patients with advanced lung malignancy but is also occasionally seen in patients with community-acquired pneumonia (CAP). There are substantial differences in the manifestations, treatment, and outcomes of post-obstructive pneumonia in these two settings. When obstruction is present in patients with CAP, it is almost always secondary to an underlying pulmonary malignancy. In fact, the observation of an obstructive component in patients with CAP leads to the detection of primary or metastatic lung cancer in more than 50% of such individuals. Post-obstructive pneumonia in patients with advanced lung malignancy is far more common (~ 50% of patients) and is associated with substantial morbidity and mortality. The management of these patients is very challenging and involves multiple disciplines including medical oncology, pulmonary medicine, infectious diseases, intervention radiology, surgery, and intensive care teams. The administration of broad-spectrum antibiotic regimens is generally required. Refractory or recurrent infections despite the administration of appropriate antimicrobial therapy are the norm. Frequent and prolonged antibiotic administration leads to the development of resistant microflora. Complications such as lung abscess, empyema, and local fistula formation develop often. Relief of obstruction generally produces only temporary symptomatic improvement.

Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity.

Effective antimicrobial agents are important arsenals in our perennial fight against communicable diseases, hospital-acquired and surgical site multidrug-resistant infections. In this study, we devise a strategy for the development of highly efficacious and skin compatible yet inexpensive water-soluble macromolecular antimicrobial polyionenes by employing a catalyst-free, polyaddition polymerization using commercially available monomers. A series of antimicrobial polyionenes are prepared through a simple polyaddition reaction with both polymer-forming reaction and charge installation occurring simultaneously. The compositions and structures of polymers are modulated to study their effects on antimicrobial activity against a broad spectrum of pathogenic microbes. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 1.95-7.8 µg/mL and high selectivity over mammalian cells. In particular, a killing efficiency of more than 99.9% within 2 min is obtained. Moreover, the polymers demonstrate high antimicrobial efficacy against various clinically-isolated multidrug-resistant microbes, yet exhibit vastly superior skin biocompatibility in mice as compared to other clinically used surgical scrubs (chlorhexidine and betadine). Microbicidal activity of the polymer is mediated via membrane lysis as demonstrated by confocal microscopy. Unlike small molecular antibiotics, repeated use of the polymer does not induce drug resistance. More importantly, the polymer shows excellent bactericidal activity in a P. aeruginosa-contaminated mouse skin model. Given their rapid and efficacious microbicidal activity and skin compatibility, these polymers have tremendous potential to be developed as surgical scrubs/hand sanitizers to prevent multidrug-resistant infections.

Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for Targeting Bacteria Residing inside Immune Cells.

In this study, a series of star-shaped polycarbonates are synthesized by metal-free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with heptakis-(2,3-di-O-acetyl)-ß-cyclodextrin (DA-ß-CD) as macroinitiator. The distributions and compositions of pendent benzyl chloride and protected mannose group (ipman) units are facilely modulated by varying the polymerization sequence and feed ratio of the monomers, allowing precise control over the molecular composition, and the resulting polymers have narrow molecular weight distribution. After deprotection of ipman groups and quaternization with various N,N-dimethylalkylamines, these star polymers with optimized compositions of cationic and mannose groups in block and random forms exhibit strong bactericidal activity and low hemolysis. Furthermore, the optimal mannose-functionalized polymer demonstrates mannose receptor-mediated intracellular bactericidal activity against BCG mycobacteria without inducing cytotoxicity on mammalian cells at the effective dose. Taken together, the materials designed in this study have potential use as antimicrobial agents against diseases such as tuberculosis, which is caused by intracellular bacteria.

Unusual non-fluorescent broad spectrum siderophore activity (SID EGYII) by Pseudomonas aeruginosa strain EGYII DSM 101801 and a new insight towards simple siderophore bioassay.

Present study highlights an unusual non-fluorescent hydroxamate broad spectrum siderophore (SID EGYII) activity from Pseudomonas aeruginosa strain EGYII DSM 101801, a soil bacterial isolate, along with simple low cost effective siderophore bioassay. Detection of SID EGYII activity qualitatively was proved by masking this activity against Erwinia amylovora strain EGY1 DSM 101800, an indicator strain, in well-cut diffusion assay containing 100 µM FeCl3. SID EGYII activity was expressed quantitatively as arbitrary units [Siderophore arbitrary units (SAU)] 380 SAU/mL against E. amylovora strain EGY1 DSM 101800. Maximal SID EGYII activity was achieved upon growing P. aeruginosa strain EGYII DSM 101801 in PYB broth at 180 rpm for 24 h. SID EGYII displayed a broad spectrum antimicrobial activity against some human pathogens (i.e., Gram-positive bacteria, Gram-negative bacteria and yeasts) and a fireblight plant pathogen. Interestingly, transformants of Escherichia coli JM109 (DE3)pSID/EGYII harboring P. aeruginosa strain EGYII DSM 101801 plasmid demonstrated a perceivable antimicrobial activity against E. amylovora strain EGY1 DSM 101800. The broad spectrum antimicrobial activity of the unusual non-fluorescent SID EGYII would underpin its high potential in targeting bacterial pathogens posing probable threats to human health and agricultural economy. The present simple low cost effective bioassay is a new insight towards an alternative to the expensive cumbersome siderophore Chrome Azurol S assay.

Neonatal group B streptococcus disease in developing countries: are we ready to deploy a vaccine?

Group B streptococcus (GBS) disease is the leading cause of neonatal sepsis in developed countries and has high case fatality rates. In developing countries, however, the burden of GBS is less clear; this is due to a lack of studies using optimal diagnostic, clinical and laboratory techniques and is complicated by the wide availability of non-prescription antibiotics to the general population and in peripartum patients. There is an urgent need for prospective, population-based surveillance to provide an accurate assessment of neonatal GBS disease burden in developing countries, which remains largely unrecognized, and consequently obscures the potential relevance of GBS vaccination in these populations. Preliminary data on GBS vaccines are promising as a preventive tool for neonatal GBS infection, more so than any other currently available public health initiative. However, how do we assess the true impact of a GBS vaccine without accurate surveillance data on the real burden of disease?

Novel water-based antiseptic lotion demonstrates rapid, broad-spectrum kill compared with alcohol antiseptic.

A novel alcohol-based antiseptic and a novel water-based antiseptic lotion, both with a synergistic combination of antimicrobial ingredients containing 0.2% benzethonium chloride, were evaluated using the standard time-kill method against 25 FDA-specified challenge microorganisms. The purpose of the testing was to determine whether a non-alcohol product could have equivalent rapid and broad-spectrum kill to a traditional alcohol sanitizer. Both the alcohol- and water-based products showed rapid and broad-spectrum antimicrobial activity. The average 15-s kill was 99.999% of the challenge organism for the alcohol-based antiseptic and 99.971% for the water-based antiseptic. The alcohol-based product demonstrated 100% of peak efficacy (60s) within the first 15s, whereas the water-based product showed 99.97%. The novel alcohol-based antiseptic reduced concentrations of 100% of organisms by 99.999%, whereas the water-based antiseptic lotion showed the same reduction for 96% of organisms. A novel water-based antiseptic product demonstrated equivalent rapid, broad-spectrum antimicrobial activity to an alcohol-based sanitizer and provided additional benefits of reduced irritation, persistent effect, and greater efficacy against common viruses. The combination of rapid, broad-spectrum immediate kill and persistent efficacy against pathogens may have significant clinical benefit in limiting the spread of disease.