Broad Antibacterial Activity Research Articles

506 A Burn Center’s Four Year Experience with a Cerium Nitrate & Silver Sulfadiazine Burn Cream

Morbidity from burn wound infection & sepsis remains high, but can be improved by early excision & grafting. However, certain situations preclude early surgery. In these cases, topical agents allow for staged excision. The combination of cerium nitrate & silver sulfadiazine (Cerium) is an inexpensive burn cream with broad antibacterial activity. It also forms an eschar over the wound that may promote reepithelialization. Methemoglobinemia (MetHba), an oft-cited side effect, is rare, but the compound is infrequently used worldwide. This is a retrospective cohort study investigating the effects of Cerium at a regional burn center. After IRB approval, patients admitted between 7/1/2014 & 7/1/2018 were screened to determine if they received Cerium. Data including demographics, burn injury & management, laboratory values & cerium application were extracted. Primary endpoints were time to surgery of Cerium-treated burns, reepithlialization & incidence of MetHba & its treatment. Of the 142 patients meeting inclusion criteria, the mean age was 56.3 & the majority were black (46%) males (67%). The most common etiologies were flame (43%), contact (25%) & scald (18%). Smoking was prevalent (28.5%). Mean TBSA was 9.9% with mean adjusted Baux score of 67.9 & APACHE II score of 10.8. 64.3% were admitted to the ICU & 10.7% had inhalation injury. Time to Cerium application was 1.67 days with 15.5 total doses received. Total TBSA treated with Cerium was 6.1% (4.5% full thickness, 1.6% partial thickness). Time to any surgery was 2.6 days whereas the time to surgery for areas treated with Cerium was 4.8 days. 10.7% of patients had treated wounds smaller than presentation at time of surgery. The mean pre-Cerium methemoglobin (MetHb) value was 1.2, while checks 12-36 h & 48-72 h post first application were 1.2 & 1.4, respectively. 9.8% developed MetHba levels >2.5%. All patients except 1 were asymptomatic. The symptomatic patient became hypoxic with MetHb of 9.4%, required reintubation, & was treated with Methylene Blue. At our center, Cerium is a well-tolerated medication with a minimal side-effect profile. Only one patient (0.7%) developed clinically significant MetHba requiring intervention. Reintubation in this patient was multifactorial as he had been extubated the same day & required frequent suctioning for copious, thick secretions, in addition to MetHba. Previous reports have described patients tolerating MetHb levels up to 31.8% without intubation. It can successfully be used to temporize burn wound excision & grafting, with our data supporting reepithelialization. Future work will study Cerium prospectively. Cerium cream is a topical dressing with few side effects which allows delayed burn excision & may improve tissue salvage.

The Genus Adonis as an Important Cardiac Folk Medicine: A Review of the Ethnobotany, Phytochemistry and Pharmacology.

The genus Adonis L. (Ranunculaceae), native to Europe and Asia, comprises 32 annual or perennial herbaceous species. Due to their cardiac-enhancing effects, Adonis spp. have long been used in European and Chinese folk medicine. These plants have been widely investigated since the late 19th century, when the cardiovascular activity of Adonis vernalis L. was noted in Europe. The present paper provides a review of the phytochemistry, biological activities and toxicology in order to highlight the future prospects of the genus. More than 120 chemical compounds have been isolated, with the most important components being cardiac glycosides as well as flavones, carotenoids, coumarins and other structural types. Plants of the genus, especially A. vernalis L. and A. amurensis Regel & Radde, their extracts and their active constituents possess broad pharmacological properties, including cardiovascular, antiangiogenic, antibacterial, antioxidant, anti-inflammatory and acaricidal activities, and exhibit both diuretic effects and effects on the central nervous system. However, most plants within the 32 species have not been comprehensively studied, and further clinical evaluation of their cardiovascular activity and toxicity should be conducted after addressing the problem of the rapidly decreasing resources. This review provides new insight into the genus and lays a solid foundation for further development of Adonis.

Green synthesis of copper oxide nanoparticles using Juglans regia leaf extract and assessment of their physico-chemical and biological properties

AbstractCopper oxide nanoparticles (CuO NPs) were green synthesized using walnut leaf extract. Effects of three synthesis parameters namely; amount copper salt (1-4 g), amount of walnut leaf extract (10-40 mL) and furnace temperature (300-500°C), on the particle size as manifested in broad absorption peak (λmax, nm), concentration (absorbance), antioxidant activity and antibacterial activity as minimum inhibitory concentration (MIC) of the fabricated CuO NPs were studied using response surface methodology, based on Box behnken experimental design. The spherical and crystalline monodispersed fabricated CuO NPs with mean particle size of 80 nm, were achieved using optimum synthesis parameters including 1 g copper salt, 14 mL walnut leaf extract and 490°C of furnace temperature. The fabricated CuO NPs at these conditions had maximum antioxidant activity of 83.64% and minimum MIC value of 1.78% w/v againstE. coli, with λmaxand absorbance values of 226 nm, 4.44% a.u., respectively.

In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii.

ObjectivesWidespread antimicrobial resistance often limits the availability of therapeutic options to only a few last-resort drugs that are themselves challenged by emerging resistance and adverse side effects. Apramycin, an aminoglycoside antibiotic, has a unique chemical structure that evades almost all resistance mechanisms including the RNA methyltransferases frequently encountered in carbapenemase-producing clinical isolates. This study evaluates the in vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii, and provides a rationale for its superior antibacterial activity in the presence of aminoglycoside resistance determinants.MethodsA thorough antibacterial assessment of apramycin with 1232 clinical isolates from Europe, Asia, Africa and South America was performed by standard CLSI broth microdilution testing. WGS and susceptibility testing with an engineered panel of aminoglycoside resistance-conferring determinants were used to provide a mechanistic rationale for the breadth of apramycin activity.ResultsMIC distributions and MIC90 values demonstrated broad antibacterial activity of apramycin against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Morganella morganii, Citrobacter freundii, Providencia spp., Proteus mirabilis, Serratia marcescens and A. baumannii. Genotypic analysis revealed the variety of aminoglycoside-modifying enzymes and rRNA methyltransferases that rendered a remarkable proportion of clinical isolates resistant to standard-of-care aminoglycosides, but not to apramycin. Screening a panel of engineered strains each with a single well-defined resistance mechanism further demonstrated a lack of cross-resistance to gentamicin, amikacin, tobramycin and plazomicin.ConclusionsIts superior breadth of activity renders apramycin a promising drug candidate for the treatment of systemic Gram-negative infections that are resistant to treatment with other aminoglycoside antibiotics.

Probiotic properties of Lactobacillus strains with high cinnamoyl esterase activity isolated from jeot-gal, a high-salt fermented seafood

Cinnamoyl esterases (CEs) improve the bioavailability of caffeic acid, a potent antioxidant with beneficial health effects. This study aimed to characterize the probiotic properties of 14 strains of CE-producing lactic acid bacteria (LAB) isolated from jeot-gal, a high-salt fermented seafood. We evaluated properties of the probiotic LAB with high CE activity, including tolerance to low pH and bile salts, antimicrobial activity, surface hydrophobicity, adhesion, and immunomodulatory effects, in vitro. All LAB tested tolerated pH 2.0 and 3% Oxgall, i.e., conditions comparable with those in the gastrointestinal environment. Three isolates, Lactobacillus paracasei JBCC10650, Lactobacillus pentosus JBCC10659, and Lactobacillus plantarum JBCC10543, showed stronger adherence to epithelial cells (12.3, 9.6, and 9.4%) than a commercial probiotic Lactobacillus rhamnosus GG (9.1%; p < 0.05), and exhibited broad antibacterial activity against putative pathogens. Most of the 14 LAB strains were able to regulate mRNA expression of pro- and anti-inflammatory cytokines in macrophages, indicating their potential immunomodulatory effects. Our findings suggest that the newly isolated CE-producing probiotics may show beneficial health effects by supporting the host immune system.

"Basal Cell Migration" in Regeneration of the Corneal Wound-Bed.

In this issue of Stem Cell Reports, Park et al. (2019) describe real-time in vivo visual monitoring of keratin-14+, Confetti-labeled limbal epithelial stem cells and their progeny as they contribute to central corneal wound-healing. The authors show that corneal wounds initially heal by “basal epithelial cell migration” into the wound-bed.

Use of a Primary Epithelial Cell Screening Tool to Investigate Phage Therapy in Cystic Fibrosis.

Antimicrobial-resistant microbes are an increasing threat to human health. In cystic fibrosis (CF), airway infections with Pseudomonas aeruginosa remain a key driver of lung damage. With few new antibiotics on the development horizon, alternative therapeutic approaches are needed against antimicrobial-resistant pathogens. Phage therapy, or the use of viruses that infect bacteria, is one proposed novel therapy to treat bacterial infections. However, the airways are complex microenvironments with unique characteristics that may affect the success of novel therapies. Here, three phages of P. aeruginosa (E79, F116, and one novel clinically derived isolate, designated P5) were screened for activity against 21 P. aeruginosa strains isolated from children with CF. Of these, phage E79 showed broad antibacterial activity (91% of tested strains sensitive) and was selected for further assessment. E79 genomic DNA was extracted, sequenced, and confirmed to contain no bacterial pathogenicity genes. High titre phage preparations were then purified using ion-exchange column chromatography and depleted of bacterial endotoxin. Primary airway epithelial cells derived from children with CF (n = 8, age range 0.2–5.5 years, 5 males) or healthy non-CF controls (n = 8, age range 2.5–4.0 years, 4 males) were then exposed to purified phage for 48 h. Levels of inflammatory IL-1β, IL-6, and IL-8 cytokine production were measured in culture supernatant by immunoassays and the extent of cellular apoptosis was measured using a ssDNA kit. Cytokine and apoptosis levels were compared between E79-stimulated and unstimulated controls, and, encouragingly, purified preparations of E79 did not stimulate any significant inflammatory cytokine responses or induce apoptosis in primary epithelial cells derived from children with or without CF. Collectively, this study demonstrates the feasibility of utilizing pre-clinical in vitro culture models to screen therapeutic candidates, and the potential of E79 as a therapeutic phage candidate in CF.

Utilization of Grape Seed Flour for Antimicrobial Lipopeptide Production by Bacillus amyloliquefaciens C5 Strain.

An endophytic Bacillus amyloliquefaciens strain called C5, able to produce biosurfactant lipopeptides with a broad antibacterial activity spectrum, has been isolated from the roots of olive tree. Optimization of antibacterial activity was undertaken using grape seed flour (GSF) substrate at 0.02, 0.2, and 2% (w/v) in M9 medium. Strain C5 exhibited optimal growth and antimicrobial activity (MIC value of 60μg/ml) when incubated in the presence of 0.2% GSF while lipopeptide production culminated at 2% GSF. Thin layer chromatography analysis of lipopeptide extract revealed the presence of at least three active spots at Rf 0.35, 0.59, and 0.72 at 0.2% GSF. Data were similar to those obtained in LB-rich medium. MALDI-TOF/MS analysis of lipopeptide extract obtained from 0.2% GSF substrate revealed the presence of surfactin and bacillomycin D. These results show that GSF could be used as a low-cost culture medium supplement for optimizing the production of biosurfactants by strain C5.

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis.

Dual-release mechanism of ethosomal gels (ie, ethosomes and gel) makes them as versatile drug delivery systems for topical applications. Clove oil is obtained from the clove buds exhibited broad antifungal and antibacterial activity. Cutaneous candidiasis is the infection caused by Candida albicans or other Candida species. The aim of the present study was to prepare ethosomal gel of clove oil and evaluate its effectiveness in the treatment of cutaneous candidiasis. Ethosomes of clove oil was formulated by using varying concentrations of soyaphosphotidyl choline and ethanol, and later, it was incorporated into carbapol 974 base gels to form ethosomal gel. The prepared ethosomal gels were also evaluated for spreadability, drug release studies, ex vivo permeation study, and antifungal activity. The optimized formulation did not cause any irritation to the skin since the pH of formulation was in the pH range of skin. The ethosomal gel showed satisfactory antifungal activity against the fungus C.albicans compared to pure clove oil. The results showed that developed formulation could be promising one in the topical delivery of clove oil for the treatment of cutaneous candidiasis.

In vitro activity of lascufloxacin, a novel fluoroquinolone antibacterial agent, against various clinical isolates of anaerobes and Streptococcus anginosus group

The in vitro activities of lascufloxacin were evaluated by comparison with seven reference compounds using 412 clinical isolates of anaerobes and Streptococcus anginosus group. Lascufloxacin showed potent and broad antibacterial activities greater than those of existing quinolones against the clinical isolates used in this study.

Antibacterial Activity of a Lytic Enzyme Encoded by Pseudomonas aeruginosa Double Stranded RNA Bacteriophage phiYY.

Multidrug-resistant Pseudomonas aeruginosa is one of the most life-threatening pathogens for global health. In this regard, phage encoded lytic proteins, including endolysins and virion-associated peptidoglycan hydrolases (VAPGH), have been proposed as promising antimicrobial agents to treat P. aeruginosa. Most dsDNA phages use VAPGH to degrade peptidoglycan (PG) during infection, and endolysin to lyse the host cells at the end of lytic cycle. By contrast, dsRNA phage encodes only one lytic protein, which is located in the viral membrane to digest the PG during penetration, and also serves as an endolysin to release the phage. Currently, there are only seven sequenced dsRNA phages, and phiYY is the only one that infects human pathogen P. aeruginosa. In this study, dsRNA phage phiYY encoded lysin, named Ply17, was cloned and purified. Ply17 contains a PG-binding domain and a lysozyme-like-family domain. Ply17 exhibited a broad antibacterial activity against the outer membrane permeabilizer treated Gram-negative bacteria. The best lytic activity was achieved at 37°C, pH 7.5, in the presence of 0.5 mM EDTA. Moreover, it could effectively lyse Gram-positive bacteria directly, including Staphylococcus aureus. Therefore, dsRNA phage encoded Ply17 might be a promising new agent for treating multidrug-resistant pathogens.

Selective Synthesis of Divergolide I.

Divergolide I (1) is a naphthoquinone ansamycin that exhibits broad antibacterial activity. Its tetracyclic ring system is believed to be biosynthetically assembled via ring contraction of a macrocyclic precursor (proto-divergolide) that is both a macrolactone and a macrolactam. We here report a convergent and enantioselective synthesis that delivers the target molecule in less than 20 linear steps. Our work establishes the absolute configuration of divergolide I, confirms its relative configuration, and demonstrates that the biomimetic cyclization of a proto-divergolide can be surprisingly selective.

Newly identified type II crustin (SpCrus2) in Scylla paramamosain contains a distinct cysteine distribution pattern exhibiting broad antimicrobial activity

Type II crustins are the most abundant type of crustins in shrimps that exhibit remarkable sequence diversities and broad antibacterial activities. This study characterized a novel type II crustin, SpCrus2, in the mud crab Scylla paramamosain. The SpCrus2 cDNA sequence is 620-bp long with a 495-bp open reading frame encoding a 164-amino acid protein. In the deduced protein, a 17-amino acid signal peptide, a glycine-rich hydrophobic region (GRR), and a cysteine-rich region (CRR) containing a whey acidic protein domain were predicted. SpCrus2 shares high similarity with most type II crustins (types IIa and IIb crustins) in shrimps but has a novel distribution pattern of cysteine residues that is distinct from most crustins. SpCrus2 and PlCrus3 from Pacifastacus leniusculus share high similarity and the same distribution pattern of cysteine residues. Thus, we proposed them as type IIc crustins. SpCrus2 is mainly distributed in the gills and can be up-regulated through Vibrio parahemolyticus or Staphylococcus aureus challenge. To investigate the biological functions of SpCrus2 and the underlying mechanisms, SpCrus2, GRR, CRR, and the mutant of CRR (CRR-M, the cysteine distribution pattern is mutated into that in most conventional crustins) were all overexpressed and purified. SpCrus2 GRR itself, as a glycine-rich amphiphilic peptide, exhibited evident antibacterial ability against Gram-negative bacteria, whereas CRR possessed potent antibacterial activity against Gram-positive bacteria. Either GRR or CRR exhibited weaker antibacterial activity than the whole protein of SpCrus2, indicating that GRR and CRR synergized to exert their potential antibacterial functions. In addition, CRR exhibited slightly stronger antimicrobial activity than CRR-M, suggesting that SpCrus2 containing this novel cysteine distribution pattern may exhibit stronger antimicrobial activity than most type II crustins with the conventional distribution pattern of cysteine residues. The likely antimicrobial ability of SpCrus2 may result from its microbial polysaccharide-binding and agglutination activities. Overall, this study characterized the first type II crustin in crabs and provided new insights into understanding the sequence and functional diversity of crustins and their immune functions in crustaceans.

Isolation and Molecular Identification of Bacteriocin-producing Enterococci with Broad Antibacterial Activity from Traditional Dairy Products in Kerman Province of Iran.

One of the critical limitations to use of bacteriocins produced by lactic acid bacteria as a substitute for chemical antibiotics is the narrow spectrum of their antibacterial activity. The aim of present study was isolation and molecular identification of bacteriocin-producing enterococci with broad antibacterial spectrum. Bacteriocin-producing bacteria were isolated from native dairies in Kerman. Bacteriocins were purified by ammonium sulfate method and the effects of them were investigated on different strains of bacteria. Also, the effects of pH and heat on produced bacteriocins were investigated. High level bacteriocin-producing isolates were identified based on molecular tests. A total of 15 strains of bacteriocin-producing Enterococcus were isolated initially. Enterococcus faecium C-2 and Y-1 strains produced bacteriocins with the highest antibacterial effect. The bacteriocins were stable in pH ranges from 2 to 12 and their antibacterial activity was maintained after autoclave treatment. The maximum bactericidal effect was observed against Listeria monocytogenes and Pseudomonas aeruginosa. In conclusion, use of these bacteriocins as a substitute for chemical antibiotics is recommended.

Biosynthesis of Neokestose Laurate Catalyzed by Candida antarctica Lipase B and Its Antimicrobial Activity against Food Pathogenic and Spoilage Bacteria.

To increase the functionality and broaden the potential application of neokestose, neokestose laurate was biosynthesized using Candida antarctica lipase B as biocatalyst, for which a mixture of 20% DMSO in 2-methyl-2-butanol (v/v) was chosen as the reaction medium. The optimum conditions for biosynthesis were as follows: a molar ratio of vinyl laurate to neokestose of 12, a temperature of 50 °C, molecular sieves of 100 g/L, and enzyme loading of 10 g/L. Under the optimal conditions, the conversion rate was achieved over 80%. The synthesized chemical 6'-O-lauroylneokestose confirmed by nuclear magnetic resonance (NMR) exhibited good emulsification with critical micelle concentration (CMC) of 352 μM and broad antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, Listeria monocytogenes, Streptococcus mutans, Bacillus subtilis, and Bacillus cereus. Conclusively, 6'-O-lauroylneokestose was evidenced to be a dual-functional agent with emulsification and antibacterial activity, showing promising application potential in the food industry.

Risk of ceftriaxone-associated pseudolithiasis during therapy for bacterial meningitis

Background: Ceftriaxone (CTRX) is frequently administered to treat bacterial meningitis because it has broad antibacterial activity, including against penicillin-resistant pneumococcus. In Japan, the CTRX therapeutic dose for bacterial meningitis is 4 g/day—higher than for infections of other organs. CTRX-associated pseudolithiasis has been reported as a rare side effect.

Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity.

The low molecular weight antimicrobial peptide GWH1 has been engineered to oligomerize as self-assembling protein-only nanoparticles of around 50nm. In this form, the peptide exhibits potent and broad antibacterial activities against both Gram-positive and Gram-negative bacteria, without any harmful effect over mammalian cells. As a solid proof-of-concept, this finding strongly supports the design and biofabrication of nanoscale antimicrobial materials with in-built functionalities. The protein-based homogeneous composition offer advantages over alternative materials explored as antimicrobial agents, regarding biocompatibility, biodegradability and environmental suitability. Beyond the described prototype, this transversal engineering concept has wide applicability in the design of novel nanomedicines for advanced treatments of bacterial infections.

Plasma-activated water: antibacterial activity and artifacts?

Broad biological activities of "plasma-activated water" (PAW) have drawn great attentions recently. Treatment of water using gas discharge plasma led to acidic solutions with excellent and broad antibacterial activity. Because PAW caused severe membrane damages in bacteria and diffused freely in extracellular matrix, PAW also demonstrated good anti-biofilm activity. However, further studies revealed that trace amounts of metal ions (mainly copper and zinc) in PAW brought by plasma treatment played key roles in bacteria inactivation. The contribution of metal ions to the antibacterial activity varied among PAWs from different working gases. However, solution acidification caused by reactive species in plasma was essential. The experimental results demonstrated that potential artifacts in reported biological activities of PAWs should be considered.

Antimicrobial effect of selected lactic acid bacteria against microorganisms with decarboxylase activity

The main purpose of this study was to evaluate the antimicrobial activity of twenty-one bacteriocinogenic lactic acid bacteria (12 strains of Lactococcus lactis subsp. lactis, 4 strains of Lactobacillus gasseri, 3 strains of Lb. helveticus and 2 strains of Lb. acidophilus, LAB) against 28 Staphylococcus and 33 Enterococcus strains able to produce tyramine, putrescine, 2-phenylethylamine and cadaverine. The antimicrobial activity of cell-free supernatants (CFS) from tested LAB was examined by an agar-well diffusion assay. Nine out of twenty-one strains (33%) showed the inhibitory effect on tested enterococci and staphylococci, namely 9 strains of Lactococcus lactis subsp. lactis. The diameters of inhibition zones ranged between 7 mm and 14 mm. The biggest diameter of 14 mm inhibition was obtained with the CFS's from strains CCDM 670 and CCDM 731 on Enterococcus sp. E16 and E28. The cell-free supernatants from Lactococcus lactis subsp. lactis CCDM 71 and from Lactococcus lactis subsp. lactis CCDM 731 displayed the broadest antibacterial activity (52% inhibition of all tested strains). On the other hand, the cell-free supernatants from the screened Lactobacillus strains did not show any inhibitory effect on the tested Staphylococcus and Enterococcus strains. Nowadays, the great attention is given to the antibacterial substances produced by lactic acid bacteria. With the ability to produce a variety of metabolites displaying inhibitory effect, the LAB have great potential in biopreservation of food.

The Inhibition Effect of Lactobacilli Against Growth and Biofilm Formation of Pseudomonas aeruginosa.

The emergence of antibiotic-resistant and food-spoilage microorganisms has renewed efforts to identify safe and natural alternative agents of antibiotics such as probiotics. The aim of this study was the isolation of lactobacilli as potential probiotics from local dairy products with broad antibacterial and anti-biofilm activities against antibiotic-resistant strains of Pseudomonas aeruginosa and determination of their inhibition mechanism. Antibiotic susceptibility and classification of acquired resistance profiles of 80 P. aeruginosa strains were determined based on Centers for Disease Control and Prevention (CDC) new definition as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) followed by antibacterial assessment of lactobacilli against them by different methods. Among the 80 P. aeruginosa strains, 1 (1.3%), 50 (62.5%), and 78 (97.5%) were PDR, XDR, and MDR, respectively, and effective antibiotics against them were fosfomycin and polymyxins. Among 57 isolated lactobacillus strains, two strains which were identified as Lactobacillus fermentum using biochemical and 16S rDNA methods showed broad inhibition/killing and anti-biofilm effects against all P. aeruginosa strains. They formed strong biofilms and had bile salts and low pH tolerance. Although investigation of inhibition mechanism of these strains showed no bacteriocin production, results obtained by high-performance liquid chromatography (HPLC) analysis indicated that their inhibitory effect was the result of production of three main organic acids including lactic acid, acetic acid, and formic acid. Considering the broad activity of these two L. fermentum strains, they can potentially be used in bio-control of drug-resistant strains of P. aeruginosa.