scholarly journals Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis

2017 ◽  
Vol 139 ◽  
pp. 665-673 ◽  
Author(s):  
Islam Eid ◽  
Mohamed M. Elsebaei ◽  
Haroon Mohammad ◽  
Mohamed Hagras ◽  
Christine E. Peters ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Bacterial Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Cell Wall ◽  
Cell Wall Synthesis ◽  
Methicillin Resistant

scholarly journals Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 543
Author(s):  
Ozioma F. Nwabor ◽  
Sukanlaya Leejae ◽  
Supayang P. Voravuthikunchai
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Bacterial Cell ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Options ◽  
Bacterial Cell Wall ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Inhibitor Compounds

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone—a novel natural antibiotic agent with a new antibacterial mechanism—could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5–1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci—both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

scholarly journals Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (3) ◽  
pp. 1127-1134 ◽  
Author(s):  
Deborah L. Higgins ◽  
Ray Chang ◽  
Dmitri V. Debabov ◽  
Joey Leung ◽  
Terry Wu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Cell Membrane Potential ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Bacterial Cell Membrane

ABSTRACTThe emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptideN,N′-diacetyl-l-lysinyl-d-alanyl-d-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistantStaphylococcus aureus, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K+. The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.

Protein expression profiles in methicillin-resistant Staphylococcus aureus (MRSA) under effects of subminimal inhibitory concentrations of imipenem

2019 ◽  
Vol 366 (15) ◽  
Author(s):  
Jichun Wang ◽  
Junrui Wang ◽  
Yanyan Wang ◽  
Peng Sun ◽  
Xiaohui Zou ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cellular Proliferation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Expression Profiles ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Gram Negative ◽  
Methicillin Resistant

ABSTRACT Imipenem is a beta-lactam antibiotic mainly active against gram-negative bacterial pathogens and also could cause cell wall impairment in methicillin-resistant Staphylococcus aureus(MRSA). However, related antibacterial mechanisms of imipenem on MRSA and mixed infections of MRSA and gram-negative bacteria are relatively poorly revealed. This study was to identify proteins in the MRSA response to subminimal inhibitory concentrations (sub-MICs) of imipenem treatment. Our results showed that 240 and 58 different expression proteins (DEPs) in sub-MICs imipenem-treated S3 (a standard MRSA strain) and S23 (a clinical MRSA strain) strains were identified through the isobaric tag for relative and absolute quantitation method when compared with untreated S3 and S23 strains, respectively, which was further confirmed by multiple reactions monitoring. Our result also demonstrated that expressions of multiple DEPs involved in cellular proliferation, metabolism and virulence were significantly changed in S3 and S23 strains, which was proved by gene ontology annotations and qPCR analysis. Further, transmission electron microscopy and scanning electron microscopy analysis showed cell wall deficiency, cell lysis and abnormal nuclear mitosis on S23 strain. Our study provides important information for understanding the antibacterial mechanisms of imipenem on MRSA and for better usage of imipenem on patients co-infected with MRSA and other multidrug-resistant gram-negative bacteria.

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