Objectives: The aim of our study was to analyse the antibiotic susceptibility of various strains of Bifidobacterium spp. to a wide range of antimicrobial agents.
Methods: Fifty strains belonging to eight species of bifidobacteria, isolated from humans, animals or probiotic products, were tested for susceptibility to 30 antibiotics by disc diffusion on Brucella agar supplemented with 5% laked sheep blood and vitamin K1 (1 mg/L). MICs of nine anti-anaerobe agents, including three new molecules (telithromycin, linezolid and gatifloxacin), were determined using the reference agar-dilution method.
Results: All strains of bifidobacteria, whatever the species, were sensitive to penicillins: penicillin G, amoxicillin (MIC(50) 0.06 mg/L), piperacillin, ticarcillin, imipenem and usually anti-Gram-positive antibiotics (macrolides, clindamycin, pristinamycin, vancomycin and teicoplanin). Susceptibility to cefalothin and cefotetan was variable. Most isolates (70%) were resistant to fusidic acid. As expected, high resistance rates were observed for aminoglycosides. Metronidazole, an agent known for its anti-anaerobe activity, was ineffective against 38% of the strains. The newly commercialized molecules, telithromycin, linezolid and gatifloxacin, were active with MIC(50)S of 1 mg/L. The only variation in susceptibility observed among the different species concerned Bifidobacterium breve, which appeared to be generally more resistant. Potentially acquired resistance was only observed against tetracycline and minocycline, in 14% of the strains.
Conclusions: With regard to a general concern about the safety of probiotics, such as potential transferability of resistance determinants, bifidobacteria, with their low natural and acquired resistance to 30 antibiotics, appear risk-free.
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http://dx.doi.org/10.1093/jac/dkh495 | DOI Listing |
Cell Discov
July 2024
Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, China.
Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties.
View Article and Find Full Text PDFMolecules
January 2023
Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China.
Structurally unrelated antibiotics MLS (macrolide-lincosamide-streptogramin B) compromised with clinically resistant pathogens because of the cross-resistance resulting from the structural modification of rRNA A2058. The structure-activity relationships of a novel 3--descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered SQ110DTC and SQ110LPTD. The conjugates of macrolides with nucleobases, especially adenine, displayed antibacterial superiority over telithromycin, azithromycin and clindamycin against rRNA A2058/2059-mutated engineered strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates.
View Article and Find Full Text PDFBioorg Med Chem Lett
July 2022
Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 102488, China; Yangtze Delta Region Academy of Beijing Institute of Technology, Jiaxing 314019, China. Electronic address:
Resistance to telithromycin and off-target effects associated with the metabolic instability present serious and challenging problems for the development of novel macrolides. Herein, studies of hybrids of macrolides and quinolones (termed macrolones) bridged with linkers from 11,12-cyclic carbamate of macrolides revealed different structure-activity relationships from the previously reported macrolones bridged with linkers derived from 6-, 9- and 4''-positions of macrolides. The optimized macrolone 34 g with a longer and rigid sidechain than telithromycin had improved metabolic stability compared to telithromycin (t: 110 vs 32 min), whose future has been heavily clouded by metabolic issues.
View Article and Find Full Text PDFLangmuir
February 2021
Biology Department, University of Maryland, College Park, Maryland 20742, United States.
The outer membrane (OM) of Gram-negative (G-) bacteria presents a barrier for many classes of antibacterial agents. Lipopolysaccharide (LPS), present in the outer leaflet of the OM, is stabilized by divalent cations and is considered to be the major impediment for antibacterial agent permeation. However, the actual affinities of major antibiotic classes toward LPS have not yet been determined.
View Article and Find Full Text PDFInt J Antimicrob Agents
November 2020
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, Zagreb, Croatia. Electronic address:
Increasing bacterial resistance to existing antibiotics presents a serious threat to human health, and new antibacterial agents are desperately needed. Unfortunately, the number of newly marketed antibiotics has decreased dramatically in recent years. Withdrawal of the macrolide antibiotic telithromycin and the inability of solithromycin to gain marketing approval have prompted our efforts to search for new anti-infective macrolide compounds.
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