scholarly journals Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Pamela Vrabl ◽  
Bianka Siewert ◽  
Jacqueline Winkler ◽  
Harald Schöbel ◽  
Christoph W. Schinagl ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
State Of The Art ◽  
Petri Dish ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Multiresistant Bacteria ◽  
Vancomycin Resistant ◽  
Art Techniques

Abstract Background With the steady increase of antibiotic resistance, several strategies have been proposed in the scientific community to overcome the crisis. One of many successful strategies is the re-evaluation of known compounds, which have been early discarded out of the pipeline, with state-of-the-art know-how. Xanthoepocin, a polyketide widespread among the genus Penicillium with an interesting bioactivity spectrum against gram-positive bacteria, is such a discarded antibiotic. The purpose of this work was to (i) isolate larger quantities of this metabolite and chemically re-evaluate it with modern technology, (ii) to explore which factors lead to xanthoepocin biosynthesis in P. ochrochloron, and (iii) to test if it is beside its known activity against methicillin-resistant Staphylococcus aureus (MRSA), also active against linezolid and vancomycin-resistant Enterococcus faecium (LVRE)—a very problematic resistant bacterium which is currently on the rise. Results In this work, we developed several new protocols to isolate, extract, and quantify xanthoepocin out of bioreactor batch and petri dish-grown mycelium of P. ochrochloron. The (photo)chemical re-evaluation with state-of-the-art techniques revealed that xanthoepocin is a photolabile molecule, which produces singlet oxygen under blue light irradiation. The intracellular xanthoepocin content, which was highest under ammonium-limited conditions, varied considerably with the applied irradiation conditions in petri dish and bioreactor batch cultures. Using light-protecting measures, we achieved MIC values against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), which were up to 5 times lower than previously published. In addition, xanthoepocin was highly active against a clinical isolate of linezolid and vancomycin-resistant Enterococcus faecium (LVRE). Conclusions This interdisciplinary work underlines that the re-evaluation of known compounds with state-of-the-art techniques is an important strategy in the combat against multiresistant bacteria and that light is a crucial factor on many levels that needs to receive more attention. With appropriate light protecting measures in the susceptibility tests, xanthoepocin proved to be a powerful antibiotic against MRSA and LVRE. Exploring the light response of other polyketides may be pivotal for re-introducing previously discarded metabolites into the antibiotic pipeline and to identify photosensitizers which might be used for (antimicrobial) photodynamic therapies.

scholarly journals In Vitro Activities of a New Ketolide, ABT-773, against Multidrug-Resistant Gram-Positive Cocci

2001 ◽  
Vol 45 (12) ◽  
pp. 3640-3643 ◽  
Author(s):  
Kavindra V. Singh ◽  
Kumthorn Malathum ◽  
Barbara E. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant ◽  
Almost All ◽  
Gram Positive Cocci

ABSTRACT The in vitro activities of ABT-773 were evaluated against 324 strains of gram-positive bacteria, including multidrug-resistantStaphylococcus spp. and Enterococcus spp. ABT-773 had lower MIC ranges, MICs at which 50% of isolates are inhibited (MIC50s), and MIC90s than erythromycin or clindamycin for almost all isolates tested. The MICs of ABT-773 were also lower than those of quinupristin-dalfopristin (Q-D) for methicillin-susceptible Staphylococcus aureus,Rhodococcus spp., and Streptococcus spp., while the MICs of Q-D were lower than those of ABT-773 for methicillin-resistant S. aureus and Enterococcus faecium, including vancomycin-resistant isolates.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

Activity of Oritavancin Against Gram-positive Pathogens Causing Bloodstream Infections in the United States Over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019)

2021 ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Helio S. Sader ◽  
Jennifer M. Streit ◽  
Mariana Castanheira ◽  
Rodrigo E. Mendes
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Bloodstream Infections ◽  
The United States ◽  
Drug Resistant ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Over Time

Oritavancin displayed potent and stable activity (MIC 90 range, 0.06-0.5 mg/L) over time (2010-2019) against Gram-positive pathogens causing bloodstream infections, including methicillin-resistant Staphylococcus aureus and resistant subsets of Enterococcus spp. Daptomycin and linezolid were also active against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus . Only oritavancin and linezolid remained active against Enterococcus faecium isolates displaying an elevated daptomycin MIC (i.e., 2-4 mg/L). Proportions of methicillin-resistant S. aureus and vancomycin-resistant Enterococcus within the respective S. aureus and enterococcal populations decreased over this period.

scholarly journals Activities of Oxadiazole Antibacterials against Staphylococcus aureus and Other Gram-Positive Bacteria

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Mrsa Strains

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.

scholarly journals In Vitro and In Vivo Activities of a Novel Cephalosporin, BMS-247243, against Organisms other than Staphylococci

2002 ◽  
Vol 46 (4) ◽  
pp. 1108-1111 ◽  
Author(s):  
Junius Clark ◽  
Joan C. Fung-Tomc ◽  
Beatrice Minassian ◽  
Yuan-Hwang Tsai ◽  
Hyekyung Yang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Resistant Species ◽  
Vancomycin Resistant

ABSTRACT BMS-247243, a novel cephalosporin inhibitory for methicillin-resistant staphylococci, primarily has activity against gram-positive bacteria. The activities of BMS-247243, cefotaxime, and ceftriaxone against streptococci and Streptococcus pneumoniae were similar. BMS-247243 inhibits Enterococcus faecalis but not Enterococcus faecium. BMS-247243 also inhibits many inherently vancomycin-resistant species (Leuconstoc, Lactobacillus, Pediococcus) and anaerobic gram-positive bacteria.

scholarly journals Comparative In Vitro Activities of Daptomycin and Vancomycin against Resistant Gram-Positive Pathogens

2000 ◽  
Vol 44 (12) ◽  
pp. 3447-3450 ◽  
Author(s):  
D. R. Snydman ◽  
N. V. Jacobus ◽  
L. A. McDermott ◽  
J. R. Lonks ◽  
J. M. Boyce
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Calcium Concentration ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Gram Positive Cocci

ABSTRACT The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistantEnterococcus faecium (VREF), methicillin-resistantStaphylococcus aureus (MRSA), methicillin-resistantStaphylococcus spp. (MRSS), and penicillin-resistantStreptococcus pneumoniae (PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 μg/ml; MRSS, 1 and 4 μg/ml; PRSP, 1 and 0.5 μg/ml; and VREF, 2 and >64 μg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.

scholarly journals Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6000
Author(s):  
Ilias Muhammad ◽  
Melissa R. Jacob ◽  
Mohamed A. Ibrahim ◽  
Vijayasankar Raman ◽  
Mallika Kumarihamy ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Polymyxin B ◽  
Synergistic Activity ◽  
Vancomycin Resistant Enterococcus ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Mrsa Strains

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6–9) and machaeridiols A-C (10–12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, −1708, −1717, −33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6–8 and 10–12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC’s, compared to 12, against MRSA 1708 and −1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5–8 µg/mL for two strains of Acinetobacter baumannii, 2–16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.

scholarly journals In vitro properties of antimicrobial bromotyrosine alkaloids

2006 ◽  
Vol 55 (4) ◽  
pp. 407-415 ◽  
Author(s):  
Neora Pick ◽  
Mamta Rawat ◽  
Dorit Arad ◽  
Jiong Lan ◽  
Junfa Fan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Lead Compound ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Monocytes And Macrophages ◽  
Natural Inhibitor ◽  
Low Toxicity ◽  
Vancomycin Resistant

A bromotyrosine alkaloid family of antimicrobial agents was synthesized using the known structure of a natural inhibitor of the mycobacterial mycothiol S-conjugate amidase (MCA) as a template. This series of compounds represents a novel class of anti-infective agents against Gram-positive pathogens, including mycobacteria and meticillin- and vancomycin-resistant Staphylococcus aureus. The fact that these compounds are active against mycobacterial strains in which the MCA gene is deleted and against Gram-positive bacteria lacking mycothiol suggests the existence of an alternative target for these compounds. One member of this family, EXEG1706, was identified as the lead compound possessing low MICs (2·5–25 μg ml−1) for several clinical isolates, whilst having low toxicity for THP-1 monocytes and macrophages.

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