scholarly journals Nitroxide functionalized antibiotics are promising eradication agents against Staphylococcus aureus biofilms

2019 ◽  
Author(s):  
Anthony D. Verderosa ◽  
Rabeb Dhouib ◽  
Kathryn E. Fairfull-Smith ◽  
Makrina Totsika
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Bacterial Biofilms ◽  
Gram Positive ◽  
Gram Negative ◽  
Microscopy Analysis ◽  
Biofilm Dispersal ◽  
Biofilm Structure ◽  
Dispersal Activity

ABSTRACTTreatment of Staphylococcus aureus biofilm-related infections represents an important medical challenge worldwide, as biofilms, even of drug-susceptible S. aureus strains, are highly refectory to conventional antibiotic therapy. Nitroxides were recently shown to induce dispersal of Gram-negative biofilms in vitro, but their action against Gram-positive bacterial biofilms remains unknown. Here we demonstrate that the biofilm dispersal activity of nitroxides extends to S. aureus, a clinically important Gram-positive pathogen. Co-administration of the nitroxide CTEMPO with ciprofloxacin significantly improved the antibiotic’s biofilm-eradication activity against S. aureus. Moreover, covalently linking the nitroxide to the antibiotic moiety further reduced ciprofloxacin’s minimal biofilm eradication concentration. Microscopy analysis revealed that fluorescent nitroxide-antibiotic hybrids could penetrate S. aureus biofilms and enter into cells localising at the surface and base of the biofilm structure. No toxicity was observed for the nitroxide CTEMPO and the nitroxide-antibiotic hybrids against human cells. Taken together, our results show that nitroxides can mediate dispersal of Gram-positive biofilms and that dual-acting biofilm-eradication antibiotics could provide broad-spectrum therapies for the treatment of biofilm-related infections.

scholarly journals Nitroxide Functionalized Antibiotics Are Promising Eradication Agents against Staphylococcus aureus Biofilms

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Anthony D. Verderosa ◽  
Rabeb Dhouib ◽  
Kathryn E. Fairfull-Smith ◽  
Makrina Totsika
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Biofilms ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Microscopy Analysis ◽  
Biofilm Dispersal ◽  
Biofilm Structure ◽  
Dispersal Activity

ABSTRACT Treatment of biofilm-related Staphylococcus aureus infections represents an important medical challenge worldwide, as biofilms, even those involving drug-susceptible S. aureus strains, are highly refractory to conventional antibiotic therapy. Nitroxides were recently shown to induce the dispersal of Gram-negative biofilms in vitro, but their action against Gram-positive bacterial biofilms remains unknown. Here, we demonstrate that the biofilm dispersal activity of nitroxides extends to S. aureus, a clinically important Gram-positive pathogen. Coadministration of the nitroxide CTEMPO (4-carboxy-2,2,6,6-tetramethylpiperidin-1-yloxyl) with ciprofloxacin significantly improved the biofilm eradication activity of the antibiotic against S. aureus. Moreover, covalently linking the nitroxide to the antibiotic moiety further reduced the ciprofloxacin minimal biofilm eradication concentration. Microscopy analysis revealed that fluorescent nitroxide-antibiotic hybrids could penetrate S. aureus biofilms and enter cells localized at the surface and base of the biofilm structure. No toxicity to human cells was observed for the nitroxide CTEMPO or the nitroxide-antibiotic hybrids. Taken together, our results show that nitroxides can mediate the dispersal of Gram-positive biofilms and that dual-acting biofilm eradication antibiotics may provide broad-spectrum therapies for the treatment of biofilm-related infections.

scholarly journals Screening of Escherichia coli Species Biodiversity Reveals New Biofilm-Associated Antiadhesion Polysaccharides

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Olaya Rendueles ◽  
Laetitia Travier ◽  
Patricia Latour-Lambert ◽  
Thierry Fontaine ◽  
Julie Magnus ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacterial Adhesion ◽  
Bioactive Molecules ◽  
Bacterial Biofilms ◽  
Gram Positive ◽  
Content Type ◽  
E Coli ◽  
Species Biodiversity

ABSTRACTBacterial biofilms often form multispecies communities in which complex but ill-understood competition and cooperation interactions occur. In light of the profound physiological modifications associated with this lifestyle, we hypothesized that the biofilm environment might represent an untapped source of natural bioactive molecules interfering with bacterial adhesion or biofilm formation. We produced cell-free solutions extracted fromin vitromature biofilms formed by 122 naturalEscherichia coliisolates, and we screened these biofilm extracts for antiadhesion molecules active on a panel of Gram-positive and Gram-negative bacteria. Using this approach, we showed that 20% of the tested biofilm extracts contained molecules that antagonize bacterial growth or adhesion. We characterized a compound, produced by a commensal animalE. colistrain, for which activity is detected only in biofilm extract. Biochemical and genetic analyses showed that this compound corresponds to a new type of released high-molecular-weight polysaccharide whose biofilm-associated production is regulated by the RfaH protein. We demonstrated that the antiadhesion activity of this polysaccharide was restricted to Gram-positive bacteria and that its production reduced susceptibility to invasion and provided rapid exclusion ofStaphylococcus aureusfrom mixedE. coliandS. aureusbiofilms. Our results therefore demonstrate that biofilms contain molecules that contribute to the dynamics of mixed bacterial communities and that are not or only poorly detected in unconcentrated planktonic supernatants. Systematic identification of these compounds could lead to strategies that limit pathogen surface colonization and reduce the burden associated with the development of bacterial biofilms on medical devices.IMPORTANCEWe sought to demonstrate that bacterial biofilms are reservoirs for unknown molecules that antagonize bacterial adhesion. The use of natural strains representative ofEscherichia colispecies biodiversity showed that nonbiocidal antiadhesion polysaccharides are frequently found in mature biofilm extracts (bacterium-free suspensions which contain soluble molecules produced within the biofilm). Release of an antiadhesion polysaccharide confers a competitive advantage upon the producing strain against clinically relevant pathogens such asStaphylococcus aureus. Hence, exploring the biofilm environment provides a better understanding of bacterial interactions within complex communities and could lead to improved control of pathogen colonization.

scholarly journals Burdock (Arctium lappa) Leaf Extracts Increase the In Vitro Antimicrobial Efficacy of Common Antibiotics on Gram-positive and Gram-negative Bacteria

2017 ◽  
Vol 15 (1) ◽  
pp. 92-102 ◽  
Author(s):  
Lucia Pirvu ◽  
Isabela Nicorescu ◽  
Cristina Hlevca ◽  
Bujor Albu ◽  
Valentin Nicorescu
Keyword(s):  
Staphylococcus Aureus ◽  
Ethanol Extract ◽  
Leaf Extracts ◽  
Gram Positive ◽  
Polyphenol Compounds ◽  
Arctium Lappa ◽  
Gram Negative ◽  
E Coli ◽  
Polar Extracts

AbstractThis work aimed to study the potential effects of four Arctii folium extracts, 5 mg gallic [GAE] acid equivalents per 1 mL sample, on six antibiotics (Ampicillin/AM, Tetracycline/TE, Ciprofloxacin/CIP, Sulfamethoxazole-Trimethoprim/SXT, Chloramphenicol/C and Gentamicin/CN) tested on four Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, and Staphylococcus epidermidis ATCC 12228) and five Gram-negative (Proteus mirabilis ATCC 29245, Escherichia coli ATCC 35218, E. coli ATCC 11229, E. coli ATCC 8739, and Bacillus cereus ATCC 11778) bacteria. Arctii folium extracts were the whole ethanol extract/W and subsequent ethyl acetate/EA, aqueous/AQ, and chloroform/CHL fractions. Chemical qualitative analysis (HPTLC method) emphasized five main polyphenol compounds in Arctii folium polar extracts: chlorogenic acid (Rf≈0.52/0.55) and its isomer, 1,5-di-O-caffeoylquinic acid (Rf≈0.90/0.92), plus cynarin (Rf≈0.77), hyperoside (Rf≈0.68/0.64) and isoquercitrin (Rf≈0.69/0.71). Microbiological screening indicated Arctii folium polar extracts (AQ and W) efficacy on S. epidermidis ATCC 12228; the MIC values were in the range of common antibiotics, being 32 and 128 μg GAE per mL sample respectively. The unpredictable effects (stimulatory or inhibitory) of Arctii folium extracts in combination with typical antibiotics as well as a potential use of the whole ethanol extract/W for restoring the antimicrobial potency of susceptible antibiotics have also been evidenced.

scholarly journals Synthesis andIn VitroAntibacterial Activity of New 2-(1-Methyl-4-nitro-1H-imidazol-5-ylsulfonyl)-1,3,4-thiadiazoles

2011 ◽  
Vol 8 (3) ◽  
pp. 1120-1123 ◽  
Author(s):  
Bahram Letafat ◽  
Negar Mohammadhosseini ◽  
Ali Asadipour ◽  
Alireza Foroumadi
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Antibacterial Activities ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Agar Dilution

In the present study we report the synthesis and antibacterial activity of a new series 2-(1-methyl-4-nitro-1H-imidazol-5-ylsulfonyl)-1,3,4-thiadiazoles (6a-c). Compounds6a-cwere testedin vitroby the conventional agar dilution method against a panel of microorganisms including gram-negative and gram-positive bacteria. Compound6bwith 5-(5-nitrofuran-2-yl)-residue on 1,3,4-thiadiazole scaffold have shown promising antibacterial activities against gram-positive bacteria includingStaphylococcus aureus, Staphylococcus epidermidisandBacillus subtilis.

scholarly journals IB-367, a Protegrin Peptide with In Vitro and In Vivo Activities against the Microflora Associated with Oral Mucositis

2000 ◽  
Vol 44 (7) ◽  
pp. 1803-1808 ◽  
Author(s):  
Deborah A. Mosca ◽  
Malinda A. Hurst ◽  
Wendy So ◽  
Beverly S. C. Viajar ◽  
Craig A. Fujii ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Oral Mucositis ◽  
Human Saliva ◽  
Systemic Absorption ◽  
Gram Positive ◽  
Oral Flora ◽  
Gram Negative ◽  
Log Reduction

ABSTRACT Although the microflora associated with oral mucositis initiated by cytotoxic therapy is not well characterized, several studies suggest that reduction of the microbial load in the oral cavity has some clinical benefit. The MICs of IB-367, a synthetic protegrin analog, ranged from 0.13 to 64 μg/ml for gram-positive bacteria (Streptococcus mitis, Streptococcus sanguis,Streptococcus salivarius, and Staphylococcus aureus) and from 0.06 to 8 μg/ml for gram-negative species (Klebsiella, Escherichia, andPseudomonas). IB-367 exhibited rapid, microbicidal activity against both log- and stationary-phase cultures of methicillin-resistant Staphylococcus aureus (MRSA) andPseudomonas aeruginosa. At concentrations near the MICs for these two organisms (4 and 2 μg/ml, respectively), IB-367 reduced viability by more than 3 logs in less than 16 min. Similarly, IB-367 effected a 4-log reduction of the endogenous microflora in pooled human saliva within 2 min at 250 μg/ml, a concentration readily attained by local delivery. After nine serial transfers at 0.5× the MIC, the MIC of IB-367 for MRSA and P. aeruginosa increased only two to four times. In a phase I clinical study with healthy volunteers, IB-367 was well tolerated, with no detectable systemic absorption. One hour after treatment with 9 mg of IB-367, the prevalence of gram-negative bacteria and yeast was reduced, and the density of the predominant gram-positive oral flora was decreased 1,000 times. IB-367's properties (speed of killing, breadth of spectrum, and lack of resistance) make the compound a strong candidate for the prophylaxis of oral mucositis. Phase II clinical trials with IB-367 are under way for this indication in immunocompromised subjects.

scholarly journals Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

2011 ◽  
Vol 110 (1) ◽  
pp. 213-224 ◽  
Author(s):  
Junjie Xing ◽  
Nurgul Moldobaeva ◽  
Anna A. Birukova
Keyword(s):  
Staphylococcus Aureus ◽  
Lung Inflammation ◽  
Endothelial Barrier ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Gram Positive ◽  
Gram Negative ◽  
Endothelial Barrier Dysfunction

Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial pathogens.

scholarly journals In VitroCytotoxic, Antioxidant, and Antimicrobial Activities ofMesua beccariana(Baill.) Kosterm.,Mesua ferreaLinn., andMesua congestifloraExtracts

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Soek Sin Teh ◽  
Gwendoline Cheng Lian Ee ◽  
Siau Hui Mah ◽  
Yoke Keong Yong ◽  
Yang Mooi Lim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacillus Cereus ◽  
Antioxidant Activities ◽  
Human Cancer ◽  
Antimicrobial Activities ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Methanol Extracts

Thein vitrocytotoxicity tests on the extracts ofMesua beccariana,M. ferrea, andM. congestifloraagainst Raji, SNU-1, HeLa, LS-174T, NCI-H23, SK-MEL-28, Hep-G2, IMR-32, and K562 were achieved using MTT assay. The methanol extracts ofMesua beccarianashowed its potency towards the proliferation of B-lymphoma cell (Raji). In addition, only the nonpolar to semipolar extracts (hexane to ethyl acetate) of the threeMesuaspecies indicated cytotoxic effects on the tested panel of human cancer cell lines. Antioxidant assays were evaluated using DPPH scavenging radical assay and Folin-Ciocalteu method. The methanol extracts ofM. beccarianaandM. ferreashowed high antioxidant activities with low EC50values of 12.70 and 9.77 μg/mL, respectively, which are comparable to that of ascorbic acid (EC50 = 5.62 μg/mL). Antibacterial tests were carried out using four Gram positive and four Gram negative bacteria onMesua beccarianaextracts. All the extracts showed negative results in the inhibition of Gram negative bacteria. Nevertheless, methanol extracts showed some activities against Gram positive bacteria which areBacillus cereus, methicillin-sensitiveStaphylococcus aureus(MSSA), and methicillin-resistantStaphylococcus aureus(MRSA), while the hexane extract also contributed some activities towardsBacillus cereus.

scholarly journals Synthesis, characterization, and in vitro antimicrobial investigation of novel pyran derivatives based on 8-hydroxyquinoline

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Mohamed Rbaa ◽  
Abdelhadi Hichar ◽  
Omar Bazdi ◽  
Younes Lakhrissi ◽  
Khadija Ounine ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Magnetic Resonance ◽  
Penicillin G ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Wide Range

Abstract Background 8-Hydroxyquinoline derivatives are known for their extensive applications in the field of analytical chemistry and separation techniques; their complexes with transition metals also exhibit antibacterial and antifungal activity. Results In the present study, we synthesized a new series of pyranoquinoline derivatives and evaluated their antibacterial activities. The structures of the synthesized compounds were characterized by Fourier transform infrared (FT-IR), hydrogen-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and elemental analysis. All the prepared compounds were evaluated in vitro as antimicrobial agents against Gram-positive and Gram-negative bacterial strains (Escherichia coli (ATCC35218), Staphylococcus aureus (ATCC29213), Vibrio parahaemolyticus (ATCC17802), and Pseudomonas aeruginosa (ATCC27853)). The screening test was determined by using the standard protocol of disc diffusion method (DDM). Conclusion We have synthesized new pyranic compounds bearing an 8-hydroxyquinoline moiety on their structure. The preliminary screening results showed that all the tested compounds have a remarkable inhibitory effect on the growth of the majority of the tested bacterial strains compared to the standard antibiotic (penicillin G), and the chlorinated compound (Q1) is more active against Gram-positive bacteria than Gram-negative bacteria such as the Staphylococcus aureus strain which is the most sensitive. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study develops novel heterocyclic compound derivatives of 8-hydroxyquinoline that have demonstrated good antibacterial activity against Gram-positive bacteria. Graphical abstract

scholarly journals In vitro activity and spectrum of LY333328, a novel glycopeptide derivative.

1997 ◽  
Vol 41 (2) ◽  
pp. 488-493 ◽  
Author(s):  
R N Jones ◽  
M S Barrett ◽  
M E Erwin
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Resistance Mechanisms ◽  
Test Methods ◽  
Species Variation ◽  
Gram Positive ◽  
Gram Negative ◽  
Staphylococcus Epidermis ◽  
Agar Dilution

Reference methods were used to determine the potency of LY333328, a semisynthetic glycopeptide derivative with a key N-alkylation substitution, against 833 strains (393 gram-positive strains and representative gram-negative bacilli) with various defined resistance mechanisms. The MICs at which 90% of the isolates are inhibited (MIC90S) (in micrograms per milliliter) of LY333328 and the percentages of strains at < or = 8 micrograms/ml were as follows: for oxacillin-susceptible Staphylococcus aureus, 2 and 100%, and for oxacillin-resistant Staphylococcus aureus, 4 and 100%; for oxacillin-susceptible Staphylococcus epidermis, 4 and 100%, and for oxacillin-resistant Staphylococcus aureus, 8 and 96%; for Streptococcus serogroups A, B, C, and G, 0.25 to 1 and 100%; for Streptococcus pneumoniae < or = 0.015 to 0.06 and 100%; for Enterococcus faecalis, 2 and 100%; and for vancomycin-susceptible Enterococcus faecium, 0.25 and 100%, and for vancomycin-resistant Enterococcus faecium, 4 and 100%. LY333328 was not active (MIC50, > or = 16 micrograms/ml) against more than 400 representative strains of Enterobacteriaceae, pseudomonads, Acinetobacter spp., Stenotrophomonas maltophilia, Haemophilus influenzae, Moraxella catarrhalis, pathogenic Neisseria spp., and anaerobic gram-negative bacilli. Gram-positive anaerobes were LY333328 susceptible (MICs, < or = 2 micrograms/ml). Test methods and conditions may have affected MICs of LY333328, with most (species variation) agar dilution MICs being greater than the broth microdilution MICs.

Sign in / Sign up

Export Citation Format

Share Document