scholarly journals Thiocillin and Micrococcin Exploit the Ferrioxamine Receptor of Pseudomonas aeruginosa for Uptake

2020 ◽  
Author(s):  
Derek C. K. Chan ◽  
Lori L. Burrows

ABSTRACTThiopeptides are a class of Gram-positive antibiotics that inhibit protein synthesis. They have been underutilized as therapeutics due to solubility issues, poor bioavailability, and lack of activity against Gram-negative pathogens. We discovered recently that a member of this family, thiostrepton, has activity against Pseudomonas aeruginosa and Acinetobacter baumannii under iron-limiting conditions. Thiostrepton uses pyoverdine siderophore receptors to cross the outer membrane, and combining thiostrepton with an iron chelator yielded remarkable synergy, significantly reducing the minimal inhibitory concentration. These results led to the hypothesis that other thiopeptides could also inhibit growth by using siderophore receptors to gain access to the cell. Here, we screened six thiopeptides for synergy with the iron chelator deferasirox against P. aeruginosa and a mutant lacking the pyoverdine receptors FpvA and FpvB. Our findings suggest that thiopeptides such as thiocillin cross the outer membrane using FoxA, the ferrioxamine siderophore receptor. Other structurally related thiopeptides did not inhibit growth of P. aeruginosa, but had greater potency against methicillin-resistant Staphylococcus aureus than thiostrepton and related thiopeptides. These results suggest that thiopeptide structures have evolved with considerations for target affinity and entry into cells.

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Amal Ramzi ◽  
Bouchra Oumokhtar ◽  
Yassine Ez zoubi ◽  
Touria Filali Mouatassem ◽  
Moussa Benboubker ◽  
...  

Background. The microbiological risk of the hospital environment, including inert surfaces, medical devices, and equipment, represents a real problem. Objective. This study is aimed at demonstrating and assessing the antibacterial activity of three synthetic disinfectants classified as quaternary ammoniums on different bacterial strains (Gram-negative and Gram-positive like Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus) isolated from the hospital environment. The reference strains included Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Pseudomonas aeruginosa ATCC 27853 used as negative control strains. Method. Three quaternary ammonium disinfectants were tested: DDN9® (0.5%) which contains didecylmethylpolyoxyethylammonium propionate as an active substance, spray (0.4%) containing quaternary ammonium compounds, and Phagosurf ND® (0.4%) with didecyldimethylammonium chloride. Their effect was evaluated using the disk diffusion technique and the broth dilution methods, allowing the Minimum Inhibitory Concentration (MIC) and then the Minimum Bactericidal Concentration (MBC). Result. Only the growth of Gram-positive bacteria and some strains of Gram-negative bacteria were inhibited by the three synthetic disinfectants. NDD9® demonstrated an antibacterial effect only against the Gram-positive strains (S. aureus and S. aureus ATCC 29213) with a MIC of 0.25 mg/ml. The disinfectant spray showed effect against all four strains including E. coli (9), S. aureus, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 with an inhibitory concentration of 4 mg/ml, while the growth of S. aureus ATCC 29213 was inhibited at 2 mg/ml. The third disinfectant, Phagosurf ND®, inhibited only the growth of S. aureus ATCC 29213 at a MIC of 4 mg/ml. Conclusion. This study is the first here in Morocco to evaluate the bacterial activity of products intended for the control of the healthcare environment. The results obtained on the three disinfectants tested reveal an ineffectiveness against some isolated strains from the hospital environment.


Author(s):  
Derek C K Chan ◽  
Lori L Burrows

Abstract Background Thiopeptides are a class of antibiotics that are active against Gram-positive bacteria and inhibit translation. They were considered inactive against Gram-negative bacteria due to their inability to cross the outer membrane. However, we discovered previously that a member of this class, thiostrepton (TS), has activity against Pseudomonas aeruginosa and Acinetobacter baumannii under iron-limiting conditions. TS hijacks the pyoverdine siderophore receptors of P. aeruginosa to cross the outer membrane and synergizes with iron chelators. Objectives To test other thiopeptides for antimicrobial activity against P. aeruginosa and determine their mechanism of uptake, action and spectrum of activity. Methods Eight thiopeptides were screened in chequerboard assays against a mutant of P. aeruginosa PA14 lacking both pyoverdine receptors. Thiopeptides that retain activity against a pyoverdine receptor-null mutant may use alternative siderophore receptors for entry. Susceptibility testing against siderophore receptor mutants was used to determine thiopeptide mechanism of uptake. Results The thiopeptides thiocillin (TC) and micrococcin (MC) use the ferrioxamine siderophore receptor (FoxA) for uptake and inhibit the growth of P. aeruginosa at low micromolar concentrations. The activity of TC required the TonB-ExbBD system used to energize siderophore uptake. TC acted through its canonical mechanism of action of translation inhibition. Conclusions Multiple thiopeptides have antimicrobial activity against P. aeruginosa, countering the historical assumption that they cannot cross the outer membrane. These results demonstrate the potential for thiopeptides to act as antipseudomonal antibiotics.


2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Anju Goyal ◽  
Sandeep Jain

A series of 1-phenyl-3-(4-(2-ethanoloxy) phenyl)-5-aryl-1H-pyrazoles were synthesized from chalcones, that is, 3-aryl-1-(4-hydroxyphenyl) prop-2-en-1-ones and studied for theirin vitroantibacterial activity. Chalcones1on reaction with phenyl hydrazine in the presence of acetic acid and few drops of hydrochloric acid yielded the corresponding 1-phenyl-3-(4-hydroxyphenyl)-5-aryl-1H-pyrazoles2which on further reaction with 2-chloroethanol furnished the title compounds3. These compounds were characterized by CHN analyses, IR, mass and1H NMR spectral data. All the compounds were evaluated for theirin vitroantibacterial activity against two Gram positive strains (Bacillus subtilisandStaphylococcus aureus) and two Gram negative strains (Escherichia coliandPseudomonas aeruginosa), and their minimum inhibitory concentration (MIC) was determined.


2009 ◽  
Vol 4 (11) ◽  
pp. 1934578X0900401 ◽  
Author(s):  
Shirley Baldovino ◽  
Janne Rojas ◽  
Luis B. Rojas ◽  
María Lucena ◽  
Alexis Buitrago ◽  
...  

The essential oil from the leaves of Monticalia andicola Turcz., collected in November 2008, was analyzed by GC/MS. A yield of 0.15% oil was obtained by hydrodistillation. Thirty-six components were identified by comparison of their mass spectra with those in the Wiley GC-MS Library data base. The major components were α-pinene (19.6%), β-pinene (10.5%), α-longipinene (6.5%), δ-3-carene (6.2%), cyperene (5.4%) and β-phellandrene (5.2%). The antibacterial activity of the essential oil was evaluated against Gram- positive (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212) and Gram-negative (Escherichia coli ATCC 25992, Klebsiella pneumoniae ATCC 23357, Pseudomonas aeruginosa ATCC 27853) bacteria, using the disc diffusion agar method. The results showed a broad spectrum of activity with minimal inhibitory concentration (MIC) values ranging from 10 to150 μg/mL.


Author(s):  
Rubal C Das ◽  
Rajib Banik ◽  
Robiul Hasan Bhuiyan ◽  
Md Golam Kabir

Macrophomina phaseolina is one of the pathogenic organisms of gummosis disease of orange tree (Citrus reticulata). The pathogen was identified from the observation of their colony size, shape, colour, mycelium, conidiophore, conidia, hyaline, spore, and appressoria in the PDA culture. The crude chloroform extracts from the organism showed antibacterial activity against a number of Gram positive and Gram-negative bacteria. The crude chloroform extract also showed promising antifungal activity against three species of the genus Aspergillus. The minimum inhibitory concentration (MIC) of the crude chloroform extract from M. phaseolina against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Shigella sonnie were 128 ?gm, 256 ?gm, 128 ?gm and 64 ?gm/ml respectively. The LD50 (lethal dose) values of the cytotoxicity assay over brine shrimp of the crude chloroform extract from M. phaseolina was found to be 51.79 ?gm/ml. DOI: http://dx.doi.org/10.3329/cujbs.v5i1.13378 The Chittagong Univ. J. B. Sci.,Vol. 5(1 &2):125-133, 2010


2021 ◽  
Vol 22 (10) ◽  
pp. 5328
Author(s):  
Miao Ma ◽  
Margaux Lustig ◽  
Michèle Salem ◽  
Dominique Mengin-Lecreulx ◽  
Gilles Phan ◽  
...  

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.


2020 ◽  
Vol 10 (2) ◽  
pp. 82
Author(s):  
Fatemeh Samieerad ◽  
Nematollah Gheibi

Background: Propolis is one of the useful bee colony products that have been used in traditional medicine for centuries. In this study, the physicochemical characters and their antibacterial effect of Iranian Propolis collected from Qazvin province was assessed.Methods: In this study, Thin Layer Chromatography and Vacuum Liquid Chromatography to detect different compounds of the extract have been used. In the initial evaluation of Propolis extract, it was found that the extract includes variable compounds with different polarity; so, the initial classification of extract with different polarity solvents was essential. Finally, 0.1 gr hydro alcoholic Propolis was injected to the HPLC by ultrasound. The antibacterial effect of Iranian ethanol extract Propolis was measured using a microdilution method against Pseudomonas aeruginosa: P. aeruginosa and Staphylococcus aureus: S.aureus standard strains and the minimum bactericidal and inhibitory concentration were defined.Results: Primary analysis of the ethanol extract by analytical Thin Layer Chromatography, demonstrated the presence of flavonoid and phenol in it. Minimum inhibitory concentration and Minimum Bactericidal Concentration for Staphylococcus aureus: S.aureus standard strain was 2.5mg/ml. The same procedure was done for Pseudomonas aeruginosa: P. aeruginosa standard strain and the Minimum inhibitory concentration and Minimum Bactericidal Concentration were 50mg/ml of Propolis extracts.  Conclusion: According to the results, the alcoholic extract of propolis from Qazvin province of Iran provides significant antimicrobial activity. Its powerful activity may be due to high total phenolic and flavonoid contents.Keywords: Iranian propolis, Antibacterial activity, Phenolic compounds, Flavonoid compound


Author(s):  
Adeyinka A. Aderinola ◽  
Jane Ejiofor ◽  
Lukmon Ogunjimi ◽  
Akanji A. Murtala ◽  
Oladapo E. Oyinloye

Effective use of antimicrobial agents for treatment/management of infectious diseases is decreasing due to emergency of multi-drug and cross resistant strains of pathogenic microbes. Medicinal plants are now increasingly used alone or as an adjunct in the management of infectious diseases as a result of their claimed efficacy and safety. This research focused on evaluating the antimicrobial potential of ethanol fruit peel extract of Mangifera indica against isolated Urinary tract infection (UTI) pathogens. Urinary tract infection (UTI) bacterial strains (staphylococcus aureus, escherichia coli and pseudomonas aeruginosa) were isolated from midstream urine of infected students using standard procedures after which the isolated Urinary tract infection pathogens were subjected to antimicrobial susceptibility test by agar-well diffusion method (Cup plate method) and the mean diameter of growth inhibition zones (n=3) of the extract at different concentrations were compared against the controls (sterile water and ciprofloxacin). Ethanol fruit peel extract of Mangifera indica significantly and dose dependently inhibit the growth of all the isolated Urinary tract infection pathogens with E.coli exhibiting the highest inhibition zone ranging from 16.83 to 28.23 mm, this was followed by pseudomonas aeruginosa with inhibition zone of 24.33 mm and staphylococcus aureus least susceptible with 22.63 diameter of zone inhibition. Ethanol fruit peel extract of Mangifera indica demonstrated a dose dependent antimicrobial activity with more pronounced effect exhibited by E. coli suggesting that the extract is more effective against gram negative bacteria despite their permeability barrier, thus suggesting Mangifera indica fruit peel as a potential candidate for the management of bacterial infections especially those caused by gram negative organisms.


2003 ◽  
Vol 23 (5) ◽  
pp. 456-459 ◽  
Author(s):  
Beth Piraino ◽  
Judith Bernardini ◽  
Tracey Florio ◽  
Linda Fried

Objective To examine gram-negative exit-site infection and peritonitis rates before and after the implementation of Staphylococcus aureus prophylaxis in peritoneal dialysis (PD) patients. Design Prospective data collection with periodic implementation of protocols to decrease infection rates in two PD programs. Patients 663 incident patients on PD. Interventions Implementation of S. aureus prophylaxis, beginning in 1990. Main Outcome Measures Rates of S. aureus, gram-negative, and Pseudomonas aeruginosa exit-site infections and peritonitis. Results Staphylococcus aureus exit-site infection and peritonitis rates fluctuated without significant trends during the first decade (without prophylaxis), then began to decline during the 1990s subsequent to implementation of prophylaxis, reaching levels of 0.02/year at risk and zero in the year 2000. Gram-negative infections fell toward the end of the 1980s, due probably to the implementation of better connectology. However, there have been no significant changes for the past 6 years. There was little change in P. aeruginosa infections over the entire time period. Pseudomonas aeruginosa is now the most common cause of catheter infection and catheter-related peritonitis. Conclusions Prophylaxis against S. aureus is highly effective in reducing the rate of S. aureus infections but has no effect on gram-negative infections. Pseudomonas aeruginosa is now the most serious cause of catheter-related peritonitis.


2006 ◽  
Vol 50 (2) ◽  
pp. 806-809 ◽  
Author(s):  
Giuseppantonio Maisetta ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
Walter Florio ◽  
Daria Bottai ◽  
...  

ABSTRACT The antimicrobial activity of human β-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.


Sign in / Sign up

Export Citation Format

Share Document