scholarly journals A New Class of Multi-Armed Antibiotics with Low Risk of Resistance

Author(s):  
Yuexiao Jia ◽  
Wenwen Chen ◽  
Rongbing Tang ◽  
Ruihua Dong ◽  
Xiaoyan Liu ◽  
...  

Abstract Antibiotic resistance of pathogenic bacteria is a serious threat to public health. New antibacterial agents with novel structures or targets are urgently needed. Here we discover a new class of multi-armed antibiotics (MAAs) structurally distinct from known antibiotics. MAAs possess a multi-armed structure composed of a nucleus like ethylene, carbon, benzene, nitrogen or triazine, and three or four symmetrical arms like phenylbenzoic acid or 4-methynylbenzoic acid. The independence from a fixed functional moiety greatly increases their molecular diversity and avoids the rapid emergence of resistance. MAAs have excellent antibacterial activities against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The action mechanism involves selective internalization into Gram-positive bacteria, inhibition of cell wall assembly and influence on cell membrane. Our study not only identifies seven potential antibiotics but also provides a completely new chemical library for future antibiotic designs. Their unique structure and multiple action mechanism alow us to develop a large family of antibiotics with low risk of resistance.

2018 ◽  
Vol 29 ◽  
pp. 70-77 ◽  
Author(s):  
Anjana Devkota ◽  
Ritu Kumari Das

Antibacterial activities of Xanthium strumarium L. (Asteraceae) was carried out in laboratory. Distilled water and methanol extracts of the leaves of plant was prepared. The antibacterial activity was studied against six pathogenic bacteria, three gram negative: Klebsiella pneumoniae (ATCC 15380), Proteus mirabilis (ATCC 49132), Escherichia coli (ATCC 25922) and three gram positive: Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25932) at different concentrations (50 mg/ml, 100 mg/ml, 150 mg/ml, 200 mg/ ml, 250 mg/ml) of leaf extracts of X. strumurium. The phytochemical screening depicted the presence of terpenoids, saponins, flavonoids, tannins and alkaloids. The antibacterial activity of extracts was determined by disc diffusion method and zone of inhibition (ZOI) was measured. Gram negative bacteria was found more resistant than gram positive bacteria. The most susceptible bacterium was S. aureus while the most resistant bacterium was E. coli. Methanolic extract was found more effective than distilled water. These findings suggest that extracts obtained from leaves of X. strumurium possess biobactericidal potential, which can suitably be exploited for making antibacterial drugs.J. Nat. Hist. Mus. Vol. 29, 2015, Page: 70-77


2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.


2014 ◽  
Vol 8 (3) ◽  
pp. 40-45
Author(s):  
Zina Hashem Shehab ◽  
Huda Suhail Abid ◽  
Sumaya Fadhil Hamad ◽  
Sara Haitham

The study was conducted to evaluate the inhibitory activity of methanol extract of Gardenia jasminoides leaves compared with leaf crude extracts for some organic solvents namely Methanol, Ethanol, Petroleum ether, Asetone and Chloroform on growth of some pathogenic bacteria and yeast, which included four gram positive isolates Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Bacillus cereus and gram negative isolates Escherichia coli, Salmonella typhi, Proteus vulgaris and Pseudomonas aeruginosa and some yeasts Candida albicans and Saccharomyces boulardii, by using well diffusion method. The inhibitory activity of extracts in the tested bacterial strains and yeasts was varied according to the type of extracting solvents and are tested microorganisms. The methanol callus extract which grown on Murashige and Skoog (MS) media by using (Naphthalen acitic acid) NAA and (Benzyle adenine) BA as growth regulator highly effective as compared to the other extracts as for inhibition of three gram positive bacteria and three gram negative bacteria,which include Staphylococcus aureus and, Proteus vulgaris, followed by acetone and ethanolic extracts which include two gram positive bacteria and two gram negative bacteria. All extracts had highly effect in growth of Candida albicans while all crude extracts didn’t show any sensitivity against Saccharomyces boulardii, and when we’d done (High Performance Liquid Chromatography) HPLC test for detection of some active compound we found Quinic acid, Iridiods glycosides and Crocin which its rate in fresh callus was higher than fresh leaves.


2020 ◽  
Vol 16 (2) ◽  
Author(s):  
P. M. Ridzuan ◽  
Hairul Aini Hamzah ◽  
Anis Shah ◽  
Norazian Mohd Hassan ◽  
Baharudin Roesnita

Antibacterial activity of different types of P. odorata leaf extracts was evaluated in combination with standard antibiotics. Persicaria. odorata leaves were extracted with n-hexane (n-hex), dichloromethane (DCM) and methanol (MeOH).  Each extract was applied on vancomycin (30µg), erythromycin (15µg) and gentamicin (10µg) discs, respectively. Disk diffusion method was used to evaluate the synergistic activity of each combination on Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, and Escherichia coli. Minimum inhibitory concentration (MIC) and gas chromatography mass spectrometry (GCMS) analysis was performed on the active extract. Synergistic effects seen were mainly from the n-hex+antibiotics combinations, mainly on the Gram-positive bacteria (7 additive, 5 antagonistic), with MIC range from 50 µg/ml to 100 µg/ml, as well as Gram-negative bacteria (2 additive, 2 indifferent, 5 antagonistic). In particular, synergism showed by the combination of n-hex+van were all additive against the susceptible bacteria. DCM extract combination showed synergistic effects on three Gram-positive species (S. aureus, S. epidermidis, S. pyogenes). Meanwhile, MeOH+antibiotics combination showed significant additive synergistic effects (p<0.05) on S. aureus and S. epidermidis.  The major compounds of leaves extract were decanal and β-citral. n-Hex extract superiorly inhibited Gram-positive bacteria growth as compared to DCM and MeOH extracts. The additive synergistic property of the n-hex P. odorata extract could be further studied for possible use as an antibacterial agent.


2016 ◽  
Vol 113 (9) ◽  
pp. 2490-2495 ◽  
Author(s):  
Daniel J. Echelman ◽  
Jorge Alegre-Cebollada ◽  
Carmen L. Badilla ◽  
Chungyu Chang ◽  
Hung Ton-That ◽  
...  

Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force. Here, we demonstrate a mechanism by which Gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops present in Ig-type CnaA domains. Using single-molecule force spectroscopy, we find that these loops of the pilus subunit SpaA of the SpaA-type pilus from Corynebacterium diphtheriae and FimA of the type 2 pilus from Actinomyces oris unfold and extend at forces that are the highest yet reported for globular proteins. Loop refolding is limited by the hydrophobic collapse of the polypeptide and occurs in milliseconds. Remarkably, both SpaA and FimA initially refold to mechanically weaker intermediates that recover strength with time or ligand binding. Based on the high force extensibility, CnaA-containing pili can dissipate ∼28-fold as much energy compared with their inextensible counterparts before reaching forces sufficient to cleave covalent bonds. We propose that efficient mechanical energy dissipation is key for sustained bacterial attachment against mechanical perturbations.


2011 ◽  
Vol 60 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Svetlana A. Ermolaeva ◽  
Alexander F. Varfolomeev ◽  
Marina Yu. Chernukha ◽  
Dmitry S. Yurov ◽  
Mikhail M. Vasiliev ◽  
...  

Non-thermal (low-temperature) physical plasma is under intensive study as an alternative approach to control superficial wound and skin infections when the effectiveness of chemical agents is weak due to natural pathogen or biofilm resistance. The purpose of this study was to test the individual susceptibility of pathogenic bacteria to non-thermal argon plasma and to measure the effectiveness of plasma treatments against bacteria in biofilms and on wound surfaces. Overall, Gram-negative bacteria were more susceptible to plasma treatment than Gram-positive bacteria. For the Gram-negative bacteria Pseudomonas aeruginosa, Burkholderia cenocepacia and Escherichia coli, there were no survivors among the initial 105 c.f.u. after a 5 min plasma treatment. The susceptibility of Gram-positive bacteria was species- and strain-specific. Streptococcus pyogenes was the most resistant with 17 % survival of the initial 105 c.f.u. after a 5 min plasma treatment. Staphylococcus aureus had a strain-dependent resistance with 0 and 10 % survival from 105 c.f.u. of the Sa 78 and ATCC 6538 strains, respectively. Staphylococcus epidermidis and Enterococcus faecium had medium resistance. Non-ionized argon gas was not bactericidal. Biofilms partly protected bacteria, with the efficiency of protection dependent on biofilm thickness. Bacteria in deeper biofilm layers survived better after the plasma treatment. A rat model of a superficial slash wound infected with P. aeruginosa and the plasma-sensitive Staphylococcus aureus strain Sa 78 was used to assess the efficiency of argon plasma treatment. A 10 min treatment significantly reduced bacterial loads on the wound surface. A 5-day course of daily plasma treatments eliminated P. aeruginosa from the plasma-treated animals 2 days earlier than from the control ones. A statistically significant increase in the rate of wound closure was observed in plasma-treated animals after the third day of the course. Wound healing in plasma-treated animals slowed down after the course had been completed. Overall, the results show considerable potential for non-thermal argon plasma in eliminating pathogenic bacteria from biofilms and wound surfaces.


2004 ◽  
Vol 59 (9-10) ◽  
pp. 657-662 ◽  
Author(s):  
Juliana B. Pretto ◽  
Valdir Cechinel-Filho ◽  
Vânia F. Noldin ◽  
Mara R. K. Sartori ◽  
Daniela E. B Isaias ◽  
...  

Abstract Calophyllum brasiliense (Clusiaceae/Guttiferae) is a native Brazilian medicinal plant traditionally used against several diseases, including infectious pathologies. Crude methanolic extracts (CME) and two fractions, denoted non-polar (soluble in chloroform) and polar (nonsoluble in chloroform), were prepared from different parts of the plant (roots, stems, leaves, flowers and fruits) and studied. The following compounds were isolated and tested against pathogenic bacteria and yeasts by determination of the minimal inhibitory concentration (MIC): brasiliensic acid (1), gallic acid (2), epicatechin (3), protocatechuic acid (4), friedelin (5) and 1,5-dihydroxyxanthone (6). The results indicated that all the parts of the plant exhibited antimicrobial activity against Gram-positive bacteria, which are selectively inhibited by components of C. brasiliense. No activity was observed against Gram-negative bacteria and yeasts tested. Regarding the isolated compounds, substance 4 showed antimicrobial activity against all the tested microorganisms, whereas compound 6 exhibited antimicrobial activity only against Gram-positive bacteria. The results from the current study confirm and justify the popular use of this plant to treat infectious processes.


1914 ◽  
Vol 19 (5) ◽  
pp. 501-512 ◽  
Author(s):  
Charles Krumwiede ◽  
Josephine S. Pratt

Several green dyes show a marked selective action for members of the typhoid-paratyphoid-colon group. This can be used for the enrichment of typhoid and paratyphoid bacilli present in feces. Forty dyes were tested with thirty strains covering all types of pathogenic bacteria. In general the dyes restrained the growth of the Gram-positive bacteria but had no effect on the growth of the Gram-negative group.


2021 ◽  
Vol 12 (2) ◽  
pp. 1824-1834

Secondary metabolites from the shoots and roots of three Rumex species collected from three different habitats were investigated (Rumex dentatus collected from cultivated land, R. pictus collected from the coastal desert and R. vesicarius collected from the inland desert) and tested for antioxidant activity as well as for anti-microbial activity against some human pathogenic bacteria. The present study indicated that the quantitative analysis of shoot and root extracts of three Rumex spp. were found to be rich in tannins and phenolics composition. The aerial parts of the three plants exhibited the highest significant values compared to the root parts. The MeOH extracts of Rumex species showed adequate antioxidant activity, wherein the IC50 values of the MeOH from the cultivated sample was 41.61 and 31.31 mg mL-1, coastal samples were 34.99 and 23.99 mg mL-1, while the sample of inland showed IC50 value of 41.59 and 31.67 mg mL-1, for root and shoot, respectively. Furthermore, using a filter paper disc assay, the MeOH extracts of the three Rumex species showed a substantial anti-microbial inhibitory effect on the growth of 10 pathogenic bacteria. According to sensitivity, the tested organisms could be sequenced as following: E. coli < K. pneumoniae ˂ S. typhi < P. aeruginosa for Gram-negative bacteria and B. subtilis < S. pneumoniae ˂ L. monocytoyenes < S. epidermis < S. aureus < B. cereus for Gram-positive bacteria. In addition, the antibacterial performance of R. dentatus root and R. vesicarius shoot MeOH extract is 100% broad spectrum against Gram-negative bacteria. A shoot of R. dentatus and R. pictus MeOH extract against Gram-positive bacteria is 83.3% broad spectrum. A further study is recommended for more characterization of the major compounds and assesses their efficiency and biosafety.


2019 ◽  
Vol 13 (11) ◽  
pp. 1013-1020
Author(s):  
Khaldoun J Al-Hadid ◽  
Nehaya Al-Karablieh ◽  
Ahmad Sharab ◽  
Ihsan Mutlak

Introduction: Resistance against commonly used antibacterial agents has become a globally recognized threat to human health. Therefore, the development of new and effective antibacterial agents is necessary to treat infections caused by resistant bacterial strains; plants are a promising source of new agents to be tested. Methodology: The minimum inhibitory concentrations (MIC) of ethanolic extracts of Erodium gruinum, Euphorbia hierosolymitana, Logoecia cuminoides, and Tamarix tetragyna against 10 Gram-negative and 5 Gram-positive bacteria were determined using agar well diffusion and microtiter plate dilution methods, respectively. The phytochemical composition of the crude extracts of the plants was determined using HPLC. Results: Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae, Proteus mirabilis, and Acinetobacter baumannii were sensitive to E. gruinum and E. hierosolymitana extracts. P. aeruginosa ATCC 27853 and M. catarrhalis were sensitive to L. cuminoides extract. P. aeruginosa ATCC 27853, P. mirabilis, and K. pneumoniae were sensitive to T. tetragyna extracts. For Gram-positive bacteria, Staphylococcus aureus ATCC 33591 and ATCC 43300 were sensitive to E. gruinum and E. hierosolymitana extracts. S. aureus ATCC 43300 and ATCC 33591 and Group D Streptococcus were sensitive to T. tetragyna extract. All Gram-positive bacteria were completely resistant to the extract of L. cuminoides. The major phytochemical components of the plant extracts belonged to flavonoids, tannins, terpenes, quinones, phytosterols, phytoestrogens, carbohydrates, fatty acids, and coumarin. Conclusion: The study showed the potential of the development of antibacterial agents from these plants. Phytochemical analysis revealed compounds that are candidates for new antibacterial drugs.


Sign in / Sign up

Export Citation Format

Share Document