Intracellular activity of antimicrobial compounds used for Staphylococcus aureus nasal decolonization

2018 ◽  
Vol 73 (11) ◽  
pp. 3044-3048 ◽  
Author(s):  
J Rigaill ◽  
M F Morgene ◽  
M Gavid ◽  
Y Lelonge ◽  
Z He ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Compounds ◽  
Intracellular Activity

scholarly journals Highlighting the Biotechnological Potential of Deep Oceanic Crust Fungi through the Prism of Their Antimicrobial Activity

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 411
Author(s):  
Maxence Quemener ◽  
Marie Dayras ◽  
Nicolas Frotté ◽  
Stella Debaets ◽  
Christophe Le Meur ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Oceanic Crust ◽  
Gene Clusters ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Antimicrobial Compounds ◽  
Human Pathogens ◽  
Biotechnological Potential ◽  
Fungal Isolates

Among the different tools to address the antibiotic resistance crisis, bioprospecting in complex uncharted habitats to detect novel microorganisms putatively producing original antimicrobial compounds can definitely increase the current therapeutic arsenal of antibiotics. Fungi from numerous habitats have been widely screened for their ability to express specific biosynthetic gene clusters (BGCs) involved in the synthesis of antimicrobial compounds. Here, a collection of unique 75 deep oceanic crust fungi was screened to evaluate their biotechnological potential through the prism of their antimicrobial activity using a polyphasic approach. After a first genetic screening to detect specific BGCs, a second step consisted of an antimicrobial screening that tested the most promising isolates against 11 microbial targets. Here, 12 fungal isolates showed at least one antibacterial and/or antifungal activity (static or lytic) against human pathogens. This analysis also revealed that Staphylococcus aureus ATCC 25923 and Enterococcus faecalis CIP A 186 were the most impacted, followed by Pseudomonas aeruginosa ATCC 27853. A specific focus on three fungal isolates allowed us to detect interesting activity of crude extracts against multidrug-resistant Staphylococcus aureus. Finally, complementary mass spectrometry (MS)-based molecular networking analyses were performed to putatively assign the fungal metabolites and raise hypotheses to link them to the observed antimicrobial activities.

scholarly journals Cellular Pharmacokinetics and Intracellular Activity of the Novel Peptide Deformylase Inhibitor GSK1322322 against Staphylococcus aureus Laboratory and Clinical Strains with Various Resistance Phenotypes: Studies with Human THP-1 Monocytes and J774 Murine Macrophages

2015 ◽  
Vol 59 (9) ◽  
pp. 5747-5760 ◽  
Author(s):  
Frédéric Peyrusson ◽  
Deborah Butler ◽  
Paul M. Tulkens ◽  
Françoise Van Bambeke
Keyword(s):  
Staphylococcus Aureus ◽  
Peptide Deformylase ◽  
Cell Fractionation ◽  
Content Type ◽  
Clinical Strains ◽  
Cellular Pharmacokinetics ◽  
Intracellular Activity ◽  
Static Concentration ◽  
Infected Cells

ABSTRACTGSK1322322 is a peptide deformylase inhibitor active againstStaphylococcus aureusstrains resistant to currently marketed antibiotics. Our aim was to assess the activity of GSK1322322 against intracellularS. aureususing anin vitropharmacodynamic model and, in parallel, to examine its cellular pharmacokinetics and intracellular disposition. For intracellular activity analysis, we used an established model of human THP-1 monocytes and tested one fully susceptibleS. aureusstrain (ATCC 25923) and 8 clinical strains with resistance to oxacillin, vancomycin, daptomycin, macrolides, clindamycin, linezolid, or moxifloxacin. Uptake, accumulation, release, and subcellular distribution (cell fractionation) of [14C]GSK1322322 were examined in uninfected murine J774 macrophages and uninfected and infected THP-1 monocytes. GSK1322322 demonstrated a uniform activity against the intracellular forms of allS. aureusstrains tested, disregarding their resistance phenotypes, with a maximal relative efficacy (Emax) of a 0.5 to 1 log10CFU decrease compared to the original inoculum within 24 h and a static concentration (Cs) close to its MIC in broth. Influx and efflux were very fast (<5 min to equilibrium), and accumulation was about 4-fold, with no or a minimal effect of the broad-spectrum eukaryotic efflux transporter inhibitors gemfibrozil and verapamil. GSK1322322 was recovered in the cell-soluble fraction and was dissociated from the main subcellular organelles and from bacteria (in infected cells). The results of this study show that GSK1322322, as a typical novel deformylase inhibitor, may act against intracellular forms ofS. aureus. They also suggest that GSK1322322 has the ability to freely diffuse into and out of eukaryotic cells as well as within subcellular compartments.

scholarly journals Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus

2015 ◽  
Vol 59 (4) ◽  
pp. 2029-2036 ◽  
Author(s):  
Florent Valour ◽  
Sophie Trouillet-Assant ◽  
Natacha Riffard ◽  
Jason Tasse ◽  
Sacha Flammier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Joint Infection ◽  
Treatment Strategies ◽  
Bactericidal Effect ◽  
Infection Model ◽  
Content Type ◽  
Intracellular Activity ◽  
Mg63 Cells ◽  
Choice Of Treatment

ABSTRACTAlthoughStaphylococcus aureuspersistence in osteoblasts, partly as small-colony variants (SCVs), can contribute to bone and joint infection (BJI) relapses, the intracellular activity of antimicrobials is not currently considered in the choice of treatment strategies for BJI. Here, antistaphylococcal antimicrobials were evaluated for their intraosteoblastic activity and their impact on the intracellular emergence of SCVs in anex vivoosteoblast infection model. Osteoblastic MG63 cells were infected for 2 h with HG001S. aureus. After killing the remaining extracellular bacteria with lysostaphin, infected cells were incubated for 24 h with antimicrobials at the intraosseous concentrations reached with standard therapeutic doses. Intracellular bacteria and SCVs were then quantified by plating cell lysates. A bactericidal effect was observed with fosfomycin, linezolid, tigecycline, oxacillin, rifampin, ofloxacin, and clindamycin, with reductions in the intracellular inocula of −2.5, −3.1, −3.9, −4.2, −4.9, −4.9, and −5.2 log10CFU/100,000 cells, respectively (P< 10−4). Conversely, a bacteriostatic effect was observed with ceftaroline and teicoplanin, whereas vancomycin and daptomycin had no significant impact on intracellular bacterial growth. Ofloxacin, daptomycin, and vancomycin significantly limited intracellular SCV emergence. Overall, ofloxacin was the only molecule to combine an excellent intracellular activity while limiting the emergence of SCVs. These data provide a basis for refining the choice of antibiotics to prioritise in the management of BJI, justifying the combination of a fluoroquinolone for its intracellular activity with an anti-biofilm molecule, such as rifampin.

scholarly journals Increased intracellular activity of MP1102 and NZ2114 against Staphylococcus aureus in vitro and in vivo

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao Wang ◽  
Xiumin Wang ◽  
Da Teng ◽  
Ruoyu Mao ◽  
Ya Hao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Intracellular Activity

Identification and Semiquantitative Estimation of Antibiotics Added to Complete Feeds, Premixes, and Concentrates

1999 ◽  
Vol 82 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Jean-Louis Gafner
Keyword(s):  
Staphylococcus Aureus ◽  
Quality Assurance ◽  
Uv Light ◽  
Acid Extraction ◽  
Antimicrobial Compounds ◽  
Routine Method ◽  
Agar Diffusion ◽  
Microbiological Methods ◽  
Layer Chromatography ◽  
Feed Samples

Abstract Classical microbiological methods for determining antimicrobial compounds in feeds are nonspecific. Thus, there is a need to identify biological activity, and bioautography is used for thispurpose. A routine method for detecting the following antimicrobial sub stances in feeds is described: avilamycin, avoparcin, Zn-bacitracin, erythromycin, flavomycin, furazolidone, lasalocid, monensin, narasin, penicillin, salinomycin, spiramycin, tetracyclines, tylosin, and virginiamycin. Carbadox can be detected by UV light examination of the plates prior to bioautography. Semiquantitative estimations of antibiotic content are compared with quantitative determinations of the above mentioned sub stances in feeds, except erythromycin, penicillin, and tetracyclines. Detection limits range from 0.1 mg/kg (chlortetracycline) to 20 mg/kg (lasalocid). The method involves agar diffusion of buffered samples, a neutral extraction of polyether antibiotics followed bythin-layer chromatography (TLC), and an acid extraction for other antibiotics followed by TLC. Five test bacteria were used for the main detection by agar diffusion: Micrococcus luteusATCC 9341, Staphylococcus aureus ATCC 6538P, Corynebacterium xerosis NCTC 9755, Bacillus cereus ATCC 11778, and B. subtilis ATCC 6633. Identification after TLC was achieved by bioautography with the most sensitive microorganism(s). This method allows one laboratory technician to analyze up to 30 feed samples within 2.5 working days, provided that feeds of the same category are analyzed in the same run, and that labels of additives are available. Qualitative and semiquantitative information are valuable when performing a quantitative antibiotic determination and it provides proof that the activity determined is due to the tested substance. This last feature is essential from the perspective of quality assurance of results.

scholarly journals Intracellular activity of trovafloxacin against Staphylococcus aureus

1999 ◽  
Vol 44 (2) ◽  
pp. 193-199 ◽  
Author(s):  
P. J. van den Broek ◽  
T. G. A. Koot ◽  
E. van Strijen ◽  
H. Mattie
Keyword(s):  
Staphylococcus Aureus ◽  
Intracellular Activity

scholarly journals Cellular Accumulation and Pharmacodynamic Evaluation of the Intracellular Activity of CEM-101, a Novel Fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in Human THP-1 Macrophages

2009 ◽  
Vol 53 (9) ◽  
pp. 3734-3743 ◽  
Author(s):  
Sandrine Lemaire ◽  
Françoise Van Bambeke ◽  
Paul M. Tulkens
Keyword(s):  
Staphylococcus Aureus ◽  
Listeria Monocytogenes ◽  
Legionella Pneumophila ◽  
Critical Role ◽  
Intracellular Accumulation ◽  
Cellular Accumulation ◽  
Intracellular Activity ◽  
P Glycoprotein

ABSTRACT CEM-101 is a novel fluoroketolide with lower MICs than those of telithromycin and macrolides. Our aim was to assess the cellular accumulation and intracellular activity of CEM-101 using models developed for analyzing the pharmacokinetics and pharmacological properties of antibiotics against phagocytized bacteria. We used THP-1 macrophages and Staphylococcus aureus (ATCC 25923 [methicillin (meticillin) sensitive]), Listeria monocytogenes (strain EGD), and Legionella pneumophila (ATCC 33153). CEM-101 reached cellular-to-extracellular-concentration ratios of about 350 within 24 h (versus approximately 20, 30, and 160 for telithromycin, clarithromycin, and azithromycin, respectively). This intracellular accumulation was suppressed by incubation at a pH of ≤6 and by monensin (proton ionophore) and was unaffected by verapamil (P-glycoprotein inhibitor; twofold accumulation increase for azithromycin) or gemfibrozil. While keeping with the general properties of the macrolide antibiotics in terms of maximal efficacy (E max; approximately 1-log10-CFU decrease compared to the postphagocytosis inoculum after a 24-h incubation), CEM-101 showed significantly greater potency against phagocytized S. aureus than telithromycin, clarithromycin, and azithromycin (for which the 50% effective concentration [EC50] and static concentrations were about 3-, 6-, and 15-fold lower, respectively). CEM-101 was also about 50-fold and 100-fold more potent than azithromycin against phagocytized L. monocytogenes and L. pneumophila, respectively. These differences in EC50s and static concentrations between drugs were minimized when data were expressed as multiples of the MIC, demonstrating the critical role of intrinsic drug activity (MIC) in eliciting the antibacterial intracellular effects, whereas accumulation per se was unimportant. CEM-101 should show enhanced in vivo potency if used at doses similar to those of the comparators tested here.

scholarly journals MIKROBA ENDOFIT DARI TANAMAN SRIKAYA (Annona squamosa L.) SEBAGAI PENGHASIL ANTIMIKROBA Staphylococcus aureus DAN Candida albicans

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Ruth Melliawati ◽  
Sunifah Sunifah
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
High Performance ◽  
Agar Medium ◽  
Agar Plate ◽  
Antimicrobial Compounds ◽  
Cyanogenic Glycosides ◽  
Annona Squamosa ◽  
Chloroform Phase ◽  
Apple Plant

Various studies indicated that endophytic microbes lived in the plant tissues and produced antimicrobial compounds. Sugar-apple plant  (Annona squamosa L) contained alkaloids, cyanogenic glycosides, and flavonoids. The purpose of this reasearch were (1) to determine the endophytic microbes isolated from sugar-apple plant (2) to study inhibiting capabillity of endophytic isolate against Staphylococcus aureus and Candida albicans, (3) to analyze antimicrobial compounds produced by the potential endophytic isolate. Diffusion agar plate methode was used to assessed antimicrobial activity. Antimicrobial compounds were analyzed by Thin Layer Chormatography (TLC) and High Performance Liquid Chormatography (HPLC), compared with erythromycin, metronidazole and tetracycline. Twelve bacterial isolates and 24 fungus were isolated. Selected bacteria, BMC 1.1, showed the biggest clear zone on C. albicans culture on agar medium, meanwhile selected fungi, BTCK 1.1T, formed the biggest colony on S. aureus culture on agar medium. TLC and HPLC analysis showed that the Rf value of BMC 1.1 and BTCK 1.1T chloroform phase fractions was similiar to metronidazole. Metronidazole concentration in C1, C2, Ck1 and Ck2 fraction were 170.98 ppm, 18.27 ppm, 1.51 ppm and 4.14 ppm respectively.

scholarly journals Optimization of Medium Fermentation for Production of Antimicrobial Compounds by Endofit Bacteria Andalas Plant (Morus macroura Miq.) B.J.T.A-6 Isolate

BioScience ◽  
2019 ◽  
Vol 3 (1) ◽  
pp. 79
Author(s):  
Nada Nafion ◽  
Dwi Hilda Putri ◽  
Irdawati Irdawati
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Endophytic Bacteria ◽  
Bacterial Resistance ◽  
Inhibition Zone ◽  
Fermentation Medium ◽  
Luria Bertani ◽  
Antimicrobial Compounds ◽  
Luria Bertani Broth ◽  
The World

Cases of bacterial resistance to antibiotics are discussed with serious problems in the world of health. New antimicrobial compounds are needed which are more effective in treating infectious diseases. Isolate B.J.T.A-6 is an endophytic bacteria from Andalas plants (Morus macroura Miq.) which is known to be able to produce antimicrobial active compounds. Antimicrobial compounds can be produced by growing them on fermented media. The purpose of this study was to optimize the medium fermentation of Andalas endophytic bacteria of B.J.T.A-6  isolates in producing antimicrobial compounds. While medium fermentation is Nutrient Broth (NB), Muller Hinton (MH), and Luria Bertani Broth (LB). Antimicrobial activity tests were carried out by means of diffusion. The parameters used were the diameter of the inhibition zone against Staphylococcus aureus around the disc paper. The profile of medium fermentation optimization was analyzed statistically. The results showed that B.J.T.A-6  isolates could inhibit the highest growth of S. aureus by using LB fermentation medium. 

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