Antibiotic Properties Research Articles

A facile and selective derivatization approach on kynurenine-NH2 in daptomycin, leading to the discovery of hexakynomycin to combat multidrug-resistant Gram-positive pathogens especially daptomycin-resistant bacteria

Wide-spread use of daptomycin unavoidably resulted in the emergence of daptomycin-resistant pathogens. In the hunt for more active daptomycin derivatives through medicinal chemistry studies, we established a concise semisynthetic approach to modify the L-Kyn13 on daptomycin specifically and effectively. Here, 19 novel derivatives with certain diversity were designed and synthesized to perform a comprehensive SAR study on this underestimated position. The optimal compound, termed “hexakynomycin”, as the new generation of daptomycin-based antibiotic candidate exhibited 4->125-fold higher activity against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE), including daptomycin-resistant strains, compared with that of daptomycin. Greater membrane binding capacity rendered hexakynomycin better activity and special antibiotic property. Hexakynomycin also demonstrated a better pharmacokinetic profile, good safety features and good pharmacodynamics properties. This work provided an effective modification strategy aiming at daptomycin which provided significant insights and showed great promise for the next generation of daptomycin derivatives.

Antibiotic Resistance/Susceptibility Profiles of Staphylococcus equorum Strains from Cheese, and Genome Analysis for Antibiotic Resistance Genes.

In food, bacteria carrying antibiotic resistance genes could play a prominent role in the spread of resistance. Staphylococcus equorum populations can become large in a number of fermented foods, yet the antibiotic resistance properties of this species have been little studied. In this work, the resistance/susceptibility (R/S) profile of S. equorum strains (n = 30) from cheese to 16 antibiotics was determined by broth microdilution. The minimum inhibitory concentration (MIC) for all antibiotics was low in most strains, although higher MICs compatible with acquired genes were also noted. Genome analysis of 13 strains showed the S. equorum resistome to be composed of intrinsic mechanisms, acquired mutations, and acquired genes. As such, a plasmidic cat gene providing resistance to chloramphenicol was found in one strain; this was able to provide resistance to Staphylococcus aureus after electroporation. An msr(A) polymorphic gene was identified in five strains. The Mrs(A) variants were associated with variable resistance to erythromycin. However, the genetic data did not always correlate with the phenotype. As such, all strains harbored a polymorphic fosB/fosD gene, although only one acquired copy was associated with strong resistance to fosfomycin. Similarly, a plasmid-associated blaR1-blaZI operon encoding a penicillinase system was identified in five ampicillin- and penicillin G-susceptible strains. Identified genes not associated with phenotypic resistance further included mph(C) in two strains and norA in all strains. The antibiotic R/S status and gene content of S. equorum strains intended to be employed in food systems should be carefully determined.

Cyanocobalamin-Modified Colistin-Hyaluronan Conjugates: Synthesis and Bioactivity.

Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 μg/mg vitamin B12 and the CT content was 335 μg/mg; they consisted of particles of two sizes, 98 and 702 nm, with a ζ-potential of approximately -25 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 μg/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30-40% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA-CT-B12 conjugates was 3.5 × 10-6 cm/s, corresponding to an in vivo intestinal absorption of 50-100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties.

Effect of Fe doped and capping agent – Structural, optical, luminescence, and antibacterial activity of ZnO nanoparticles

Zinc oxide nanoparticles (ZnO NPs) are indispensable materials for spectral and optical phenomena, prepared by a chemical precipitation method. We studied their properties resulting from different dopants in the nanoscale. The samples' structure, texture, energy band, and photoluminescence were examined using XRD, TEM, FTIR, PL, and UV–VIS spectroscopy. XRD shows the single hexagonal Wurtzite with crystallite sizes from 10.1 to 17.8 nm and the spherical shape particles. The octahedral sites at 470–489 cm−1 and the tetrahedral sites at 616 cm−1 were observed in the FTIR studies. PL showed a wider bandgap, better UV emission, and decreased defect density of the Fe doped than that of the pristine one. Fe-doped ZnO NPs are more active than pristine ZnO NPs for their quenching or absorbing properties, indicating their antibiotic properties.

Potential of Sunda Porcupine (Hystrix javanica) Quills Extract as a Wound Healing Medicine: A Review of the Bioactive Components and Mechanisms

Sunda porcupine (Hystrix javanica), a native species of Indonesia, is renowned for its distinctive sharp quills enveloping its body. Despite its reputation as a spiky creature, the use of porcupine quills in traditional medicine in Indonesian society, especially for toothache and stomach ulcers, shows that there are benefits as an alternative to herbal medicine that has yet to be fully explored. Even outside Indonesia, North American porcupine quills are reported to have antibiotic properties related to the free fatty acids that coat the spines. Extracts of Sunda porcupine quills have also shown interesting antibacterial activity. Several bioactive compounds have been found in Sunda porcupine quills extract, including alkaloids, flavonoids, saponins, steroids, triterpenoids, and peptides. These compounds have various health benefits, such as analgesic, anti-inflammatory, and antimicrobial. In addition, the antibacterial activity test on the extract showed strong potential against the growth of gram-positive bacteria. The activities of secondary metabolites that play a role in helping wound healing are anti-inflammatory, antioxidant, and antibacterial/antimicrobial activities. Wound healing mechanisms involve several complex interactions of various cellular and molecular processes. Recent research has revealed the great potential of extracts from Sunda porcupine quills as a wound healing medicine. Although the potential of Sunda porcupine quills extract as a wound healing medicine has attracted attention, this research still has limitations. Critical measures, such as in vivo and in vitro testing, still need to be improved, leaving gaps in information that require further research. The challenge of an in-depth understanding of the activity and mechanisms of bioactive compounds is the focus on optimizing the utilization of Indonesia's natural potential. This article reviews the bioactive components of Sunda porcupine quills extract and their mechanism as a wound healing agent.

Manilkara zapota "chicozapote" as a fruit source of health-beneficial bioactive compounds and its effects on chronic degenerative and infectious diseases, a review.

Manilkara zapota "chicozapote" is an autochthonous evergreen tree from the Southern regions of Mexico, Belize, and Guatemala. Currently, it is widely distributed and extensively grown in Mexico and Southeast Asia. Traditionally, different structures of the plant have been used for medical purposes; seeds have diuretic and purgative properties, aiding in digestive complications and eliminating bladder and kidney stones. Tree bark has antidiarrheal, antipyretic, antibiotic, and astringent properties. Fruits and leaves have been used to treat cold, cough, diarrhea, indigestion, fever, hemorrhages, wounds, and ulcers. Chicozapote fruit is yellow and brown, with an oval shape and rough peel, it is an excellent source of nutrients, such as sugars, proteins, amino acids, and minerals, and is rich in phytochemical components, such as flavonoids, phenolic acids, and tannins. These bioactive compounds exert several biological activities, i.e., as an antioxidant, antidiabetic, antimicrobial, anti-inflammatory, cytotoxic, and anti-arthritic agents, to name a few. These beneficial properties assist in preventing chronic and degenerative diseases, such as cancer, diabetes, neurological, infectious, and cardiovascular diseases. The use of chicozapote is still limited to its fresh form, and its non-edible structures produce a lot of waste. Therefore, an alternative valorizing and preserving strategy is to use the fruit as a raw source to design functional foods and pharmacological products. Here, the nutritional and phytochemical profiles and the current view regarding methodologies and conditions, for the extraction and characterization of its bioactive compounds, are described, and focus is placed on their multiple biological effects and specific functional mechanisms.

Macrophage infectivity potentiator protein, a peptidyl prolyl cis-trans isomerase, essential for Coxiella burnetii growth and pathogenesis.

Coxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available human vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyse the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria. To date the role of the Mip protein in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. The pipecolic acid derived compounds, SF235 and AN296, which have shown utility in targeting other Mip proteins from pathogenic bacteria, demonstrate inhibitory activities against CbMip. These compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain in axenic culture. Comparative proteomics, in the presence of AN296, revealed alterations in stress responses with H2O2 sensitivity assays validating that Mip inhibition increases the sensitivity of C. burnetii to oxidative stress. In addition, SF235 and AN296 were effective in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for replication and that the development of more potent inhibitors against CbMip is warranted and offer potential as novel therapeutics against this pathogen.

Characterization of Staphylococcus aureus and methicillin‐resistant S. aureus from yak

AbstractStaphylococcus aureus, particularly methicillin‐resistant S. aureus (MRSA), is an important zoonotic pathogen which not only causes significant economic loss in livestock production but also emerges as a potential threat to public health. Compared with bovines, the information on the colonization of S. aureus and MRSA in yaks, the only bovine species providing meat and other necessities for Tibetans living at high altitude, is very limited. Therefore, in the current study, S. aureus and MRSA prevalence, virulence genes, and antibiotic and antiseptic resistance properties in yaks from 18 counties of Ganzi Prefecture, Sichuan province, China were investigated. The results revealed that the overall prevalence of S. aureus during yak breeding was 7.10% among 1281 samples (91/1281), containing 9.44% from nasal (62/657) and 4.65% from anus (29/624). Nearly all of the S. aureus isolates carried at least one staphylococcal enterotoxin (SE) gene and the predominant enterotoxin gene was selx (51.65%). In addition, virulence genes (hlα, hlβ, pvl, and tsst‐1), antiseptic resistance genes (qacA/B, qacC, and qacG), and heavy metal resistance genes (copA, arsB, cadD, and arsA) were also found. Furthermore, 24 MRSA strains were identified. SCCmec, spa, and multilocus sequence typing typing revealed that the predominant types of MRSA were ST59‐IVa‐t437 and ST59‐III‐t437. It was noteworthy that all these methicillin‐resistant strains were resistant to two or more antibiotics and possessed virulence genes. The minimal inhibitory concentration (MIC) values of antiseptic peroxyacetic acid, sodium hypochlorite, and benzalkonium bromide against these MRSA strains were measured and the MIC values of benzalkonium bromide (1.22–9.77 μg/mL) were relatively low. Furthermore, the challenge with 1/4 MIC of oxacillin sodium or ofloxacin or benzalkonium bromide for 216 h increased the resistance of the MRSA strain YB786 to these antibiotics but decreased the MIC value of benzalkonium bromide. The results provide an indication of the health risks associated with these S. aureus strains, especially methicillin‐resistant strains from yaks and new approaches are needed to treat these strains.

Antibacterial Activity of CdTe/ZnS Quantum Dot-β Lactum Antibiotic Conjugates.

β-Lactum antibiotics are broad class of antibiotics which kills bacteria by inhibiting the formation of peptidoglycan that constitutes the bacterial cell wall. The resistance that develops in bacteria for antibiotics led the scientific world to think about the future aspects for modifying the way through which antibiotics are acted on the bacteria and become lethal for them. In this consequence, the potential of latest marketed antibiotics e.g. Amoxiciline (I), ceftazidim (II) have been evaluated after being conjugated with quantum dots. The surface of quantum dots has been conjugated with antibiotics by carbodiimide coupling with the help of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as conjugating agent between antibiotic and functionalized quantum dots. The antibacterial properties of QD-conjugated antibiotics have been determined by disc diffusion assay. The potency of QD-conjugated antibiotics has been estimated by determining their MIC50 for the selected strain of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Minimum inhibitory concentration study, minimum bactericidal concentration and growth pattern analysis revealed that QD-antibiotic conjugates showed slightly more prospective than pure native antibiotics against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria.

Antibacterial and antibiotic potentiating capabilities of extracts isolated from Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus against human pathogenic bacteria.

Antibiotics which once a boon in medicine and saved millions of lives are now facing an ever-growing menace of antibacterial resistance, which desperately needs new antibacterial drugs which are innovative in chemistry and mode of action. For many years, the world has turned to natural plants with antibacterial properties to combat antibiotic resistance. On that basis, we aimed to identify plants with antibacterial and antibiotic potentiating properties. Seventeen different extracts of 3 plants namely Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus were tested against multi-drug resistant Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillinresistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). Antibacterial activity of hexane, methanol and chloroform extracts of bark, seed, fruit, flesh and leaves from these plants were tested using, disk diffusion assay, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Antibiotic potentiating capabilities were tested using time-kill assay. B. malaccensis fruit chloroform extract showed the biggest zone of inhibition against MRSA (13.00±0.0 mm) but C. bracteosus bark methanol extract showed the biggest inhibition zone against MSSA (15.33±0.6 mm). Interestingly, bark methanol extract of C. bracteosus was active against MRSA (8.7±0.6 mm), MSSA (7.7±0.6 mm) (Gram-positive) and A. baumannii (7.7±0.6 mm) (Gram-negative). Overall, the leaf methanol and bark methanol extract of C. bracteosus warrants further investigation such as compound isolation and mechanism of action for validating its therapeutic use as antibiotic potentiator importantly against MRSA and A. baumannii.

Sustainable Use of Waste Banana Peel (Musa × sapientum L.) Powder for Enhancement of Nutritional Properties of Dark Chocolate

Dark chocolate is a very popular confectionary product among children, made by combining cocoa (55%) with cocoa butter (7.5%) and sugar (42%) has high antioxidant, anti-inflammatory, and free-radical scavenging properties. Chocolates also have a high concentration of cocoa and flavanols contents which is very beneficial for human health. The nutritional value of the dark chocolate samples prepared was further enhanced by using unripe banana peel powder. The peel of banana fruit is a waste material, but it also has antioxidant, antibacterial, and antibiotic properties which encourages its use in industries like pharmaceuticals. So, after considering the nutritional value of unripe banana fruit peel, the powder of unripe banana peel was added to the dark chocolate in the concentration of 1, 3, 5, 7, and 9% to increase the nutritional value of dark chocolate. The premix powder containing iron, folic acid, and vitamin B12 was also added to the dark chocolate samples in the concentration of 2% in all the variants. The nutritional value of chocolate samples made by using unripe banana peel powder and premix increased significantly but the color of the product decreased significantly as the concentration of banana powder increased.

Bioefficacy of Lecanoric Acid Produced by Parmotrema austrosinense (Zahlbr.) Hale against Tea Fungal Pathogens

Lichens are symbiotic organisms that are composed of fungal partners and photosynthetic algal partners. During the symbiotic process in lichen thallus, the fungus synthesizes certain secondary metabolites in which lecanoric acid is very important in terms of antibiotic properties. Considering the vital importance of lecanoric acid, the present study aimed to produce lecanoric acid from the thallus of Parmotrema austrosinense lichen using Modified Bold’s basal salt medium and evaluate the bio-efficacy against tea fungal pathogens. Lecanoric acid was purified and confirmed by micro-crystallization method and subsequently bioassayed against tea fungal pathogens. The results revealed that lecanoric acid registered a significant antifungal activity in terms of the growth inhibition of test pathogens. Companion systemic and botanical fungicides were found to be inferior to lecanoric acid in the percentage of growth inhibition. The inhibition rate varied among tea pathogens. Of the tea pathogens tested, tea leaf disease-causing pathogens including Cercospora theae (C. theae), Glomerella cingulata (G. cingulate), and Phomopsis theae (P. theae) showed the highest percentage of growth inhibition followed by stem and root rot diseases. The present study suggests that lecanoric acid showed an inhibitory effect against tea pathogens, which might be due to antibiotic properties and fungicidal action of lecanoric acid.

Mechanistic Insights into Roseoflavin Synthesis by N,N-8-Demethyl-8-aminoriboflavin Dimethyltransferase (RosA): Molecular Dynamics Simulations and Residue Conservation Analysis.

8-Demethyl-8-dimethylaminoriboflavin (Roseoflavin or RoF) is a natural riboflavin analogue found in Streptomyces davaonensis and Streptomyces cinnabarinus. RoF displays potent antibiotic properties because it affects FMN riboswitches and flavoproteins of cellular targets. N,N-8-Demethyl-8-aminoriboflavin dimethyltransferase (RosA) is an enzyme that catalyzes the last step of RoF biosynthesis, a consecutive dimethylation of 8-demethyl-8-aminoriboflavin (AF) to generate RoF. Thus, understanding mechanistic insights into RosA structures and mechanisms could lead to the improvement of the RoF product yield. Herein, mechanistic insights into roseoflavin synthesis by RosA were evaluated using molecular dynamics simulations. The obtained results revealed that RosA possibly catalyzes the reaction by positioning the substrate binding to have proper distance and orientation to the methyl group donor, S-adenosylmethionine. No direct participation of catalytic residues in the reaction was identified. The enzyme's active site structures change drastically to accommodate the ligand binding. On the basis of the MM/GBSA calculations and conservation analysis, the amino acid residues involved in substrate binding were identified. The structural information obtained from this study could be beneficial in designing RosA to efficiently produce roseoflavin.

Antibacterial activities of water extract of Vernonia amygdalina Delile leaves

Staphylococci are common bacterial colonizers of the skin and mucous membranes of humans and other mammals. Staphylococcus epidermidis in particular is the most frequently isolated species from human epithelia. It colonizes predominantly the axillae, head, and nares. One type of medicinal plant that is nutritious for health is African leaves (Vernonia amygdalina Delile). Vernonia amygdalina extract showed the presence of some compounds which are rich in those constituents. The phytochemical screening of the extracts showed variation in their phytochemical constituents with the presence and or absence of some components. The presence of glycosides, alkaloids, and flavonoids was believed to exhibit the antibiotic properties of V. amygdalina leaves and confirmed their antimicrobial efficacy against selected pathogens. The concentration of 50 mg/mL up to a concentration of 1.56 mg/mL can inhibit the growth of S. epidermidis, the Minimum Inhibitory Concentration (MIC) itself is at the smallest concentration that has been able to inhibit bacterial growth and the number of bacteria is < 10 colonies. Staphylococcus epidermidis at a concentration of 25 mg/mL, absorbance values at wavelengths of 260 nm and 280 nm were higher than the absorbance values of S. epidermidis at a concentration of 12.5 mg/mL. The absorbance value at wavelengths of 260 nm and 280 nm will increase with the higher concentration of the extract, this indicates the presence of cell leakage observed in the presence of protein and nucleic acid leakage. S. epidermidis biofilm inhibition test shows that the results of the absorbance or OD (Optical Density) measurement in the biofilm inhibition test using the ethanol extract of V. amygdalina Delile, the OD value at a concentration of 25 mg/mL ie 0.149±0.004 showed a biofilm inhibition result of 62.37% greater than the concentration of 12.5 mg/mL which is 0.318±0.003 with a biofilm inhibition result of 19.52%, this indicates that the higher the concentration of the extract, the smaller the biofilm formation of S. epidermidis bacteria.

Co-interaction of nitrofuran antibiotics and the saponin-rich extract on gram-negative bacteria and colon epithelial cells

Large-scale use of nitrofurans is associated with a number of risks related to a growing resistance to these compounds and the toxic effects following from their increasing presence in wastewater and the environment. The aim of the study was to investigate an impact of natural surfactant, saponins from Sapindus mukorossi, on antimicrobial properties of nitrofuran antibiotics. Measurements of bacterial metabolic activity indicated a synergistic bactericidal effect in samples with nitrofurantoin or furazolidone, to which saponins were added. Their addition led to more than 50% greater reduction in viable cells than in the samples without saponins. On the other hand, no toxic effect against human colon epithelial cell was observed. It was found that exposure to antibiotics and surfactants caused the cell membranes to be dominated by branched fatty acids. Moreover, the presence of saponins reduced the hydrophobicity of the cell surface making them almost completely hydrophilic. The results have confirmed a high affinity of saponins to the cells of Pseudomonas strains. Their beneficial synergistic effect on the action of antibiotics from the nitrofuran group was also demonstrated. This result opens promising prospects for the use of saponins from S. mukorossi as an adjuvant to reduce the emission of antibiotics into the environment.

Pharmacokinetic Analysis of Zonarol, a Marine Algal Hydroquinone, in Mice Using HPLC with Fluorescence Detection

Zonarol, which was discovered in the brown algae Dictyopteris undulata, has antibiotic, antioxidative, anti-inflammatory, and neuroprotective hydroquinone properties. Additionally, a daily treatment of zonarol taken orally has been proven to prevent ulcerative colitis and nonalcoholic fatty liver disease in experimentally induced mice models. In this study, to elucidate the physiological behavior of zonarol in vivo, the establishment of quantitative methods for the determination of zonarol in biological samples and basic pharmacokinetics parameters after oral or intravenous administration with purified zonarol to mice were investigated. The zonarol (20–600 ng/mL) in this study was dose-dependently detected using an HPLC-FI system as a single peak on the ODS column with 80% aqueous methanol at 332 nm with an excitation of 293 nm. The pharmacokinetic parameters were derived from a non-compartment analysis of the plasma concentration of zonarol following oral or intravenous treatment in mice. The absolute bioavailability of zonarol was calculated as 25.0%. Interestingly, the maximal distribution of zonarol in the brain (2.525 ± 1.334 µg/g tissue) at 30 min was observed to be higher and slower than that in the liver and kidney at 15 min after bolus intravenous administrations to the mice (10 mg/kg BW). Based on these results, zonarol might be a candidate for a potential drug, an effective tool for drug delivery, or enhancing the treatment of cerebral disease.

Benzo[j]fluoranthene-Derived Natural Products.

In this overview the literature on benzo[j]fluoranthene-derived toxins produced by fungi is discussed with a view on isolation, structure, biological activities, biosynthesis, and total syntheses of the natural products. This class of compounds consists until now of 33 naturally occurring compounds, where 25 are chiral and eight contain no stereogenic centers. The relative configuration of xylarenol was clarified by comparison of experimental and calculated ECD spectra, and absolute configurations of four toxins were corrected. The compounds show various biological activities including antibiotic and cytotoxic properties.

Structure-Activity Relationship Studies of Indolglyoxyl-Polyamine Conjugates as Antimicrobials and Antibiotic Potentiators.

Antibiotic resistance is a growing global health threat, requiring urgent attention. One approach to overcome antibiotic resistance is to discover and develop new antibiotic enhancers, molecules that work with legacy antibiotics to enhance their efficacy against resistant bacteria. Our previous screening of a library of purified marine natural products and their synthetic analogues led to the discovery of an indolglyoxyl-spermine derivative that exhibited intrinsic antimicrobial properties and was also able to potentiate the action of doxycycline towards the difficult to treat, Gram-negative bacterium Pseudomonas aeruginosa. A set of analogues have now been prepared, exploring the influence of indole substitution at the 5- and 7- positions and length of the polyamine chain on biological activity. While limiting cytotoxicity and/or hemolytic activities were observed for many analogues, two 7-methyl substituted analogues (23b and 23c) were found to exhibit strong activity towards Gram-positive bacteria with no detectable cytotoxicity or hemolytic properties. Different molecular attributes were required for antibiotic enhancing properties, with one example identified, a 5-methoxy-substitiuted analogue (19a), as being a non-toxic, non-hemolytic enhancer of the action of two tetracycline antibiotics, doxycycline and minocycline, towards P. aeruginosa. These results provide further stimulation for the search for novel antimicrobials and antibiotic enhancers amongst marine natural products and related synthetic analogues.

Etiology of bacterial community-acquired pneumonia among hospitalized children in Hai Phong Children’s Hospital

The objectives of this study were to determine the etiology of bacterial community-acquired pneumonia (CAP) in children hospitalized at Hai Phong Children’s Hospital (HCH) in 2019 and these bacteria’s antibiotic resistance properties. The subjects were the qualified medical records of all inpatients at the Respiratory Department of Hai Phong Children’s Hospital aging from 1 month to 15 years old diagnosed with CAP according to the diagnostic criteria of the World Health Organization with positive nasopharyngeal swab culture results from January 1st, 2019, to December 31st, 2019. The sample size included all medical records of patients who met the inclusion criteria of this research during the study period. The success rate of nasopharyngeal swab culture test of CAP patients was 638/1605 (39.7%). The most common pathogens of CAP in children at HCH were S. aureus, S. pneumoniae, H. influenzae and M. catarrhalis. Antibiogram revealed that each of them showed high resistance to a various type of antibiotics. Our study also provided valuable data on the antibiotic sensitivity and raised alarm over presence of multidrug-resistant bacteria inducing CAP in children.

Identification of prevalence and antibiotic resistance property as a basis for establishing an efficient treatment of bacteria causing mastitis in beef cows

The purpose of the study was to examine the occurrence of metritis on reproduction of beef cows. A total of 2,962 cows were examined, and samples were collected from those displaying clinical symptoms of bovine metritis for bacterial analysis. Bacterial species identification was performed using culture and PCR techniques. The findings revealed that bovine metritis affected 5.5% of the reproductive cow population with the presence of Streptococcus spp., Staphylococcus aureus, Escherichia coli, and Salmonella spp. at the rates of 87.7%, 61.1%, 59.9% and 17.3%, respectively. The results also demonstrated that Streptococcus spp. was the most prevalent group, while Salmonella spp. had the lowest prevalence across different breeds and litters. However, in the Limousin crossbred cows, the infection rate of E. coli surpassed that of the other bacteria and a significantly higher infection rate for E. coli was observed in litter 4 and litter ≥6 compared to the others. The disk diffusion method was utilized to assess antibiotic resistance patterns of the isolated bacteria. Among the bacteria, marbofloxacin exhibited the lowest prevalence of antibiotic resistance (16.9%), while doxycycline had the highest prevalence (82.2%). All cows recovered from the disease within 3-5 days of treatment, and all of them resumed estrus in the subsequent reproductive cycle. The pregnancy rate ranged from 66.7% to 80.0% for the first insemination in the next reproductive cycle.