Searching for mechanisms of action of antimicrobials

Polo, Ana Bárbara; Fabri, Rodrigo Luiz; Apolônio, Ana Carolina Morais

doi:10.1007/s00203-020-01959-z

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…The rapid emergence of resistant bacteria then requires the development of new strategies to increase the efficacy of antibiotics. The phenomenon of resistance is strictly related to the mechanism of action of the antimicrobial agents, and the identification of the specific vital microbial functions they are targeting is pivotal when looking for new pharmacological tools to fight resistant bacteria [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Somma

Canè

Rotondo

et al. 2023

IJMS

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Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ Km (at 40 μM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (Kd = 26.6 nM). The in vitro results were in agreement with docking simulation studies.

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Section: Introductionmentioning

confidence: 99%

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Somma

Canè

Rotondo

et al. 2023

IJMS

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Antioxidant, antimicrobial and cytotoxic properties of Diospyros lotus L. essential oil with supercritical fluid extraction

Wang,

Ma,

et al. 2024

Food Measure

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Pseudomonas aeruginosa: a clinical and genomics update

Pelegrin

Palmieri

Mirande

et al. 2021

FEMS Microbiology Reviews

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Antimicrobial resistance (AMR) has become a global medical priority that needs urgent resolution. Pseudomonas aeruginosa is a versatile, adaptable bacterial species with widespread environmental occurrence, strong medical relevance, a diverse set of virulence genes and a multitude of intrinsic and possibly acquired antibiotic resistance traits. P. aeruginosa causes a wide variety of infections and has an epidemic-clonal population structure. Several of its dominant global clones have collected a wide variety of resistance genes rendering them multi-drug resistant (MDR) and particularly threatening groups of vulnerable individuals including surgical patients, immunocompromised patients, Caucasians suffering from cystic fibrosis (CF) and more. AMR and MDR especially are particularly problematic in P. aeruginosa significantly complicating successful antibiotic treatment. In addition, antimicrobial susceptibility testing (AST) of P. aeruginosa can be cumbersome due to its slow growth or the massive production of exopolysaccharides and other extracellular compounds. For that reason, phenotypic AST is progressively challenged by genotypic methods using whole genome sequences (WGS) and large-scale phenotype databases as a framework of reference. We here summarize the state of affairs and the quality level of WGS-based AST for P. aeruginosa mostly from clinical origin.

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Searching for mechanisms of action of antimicrobials

Cited by 3 publications

References 48 publications

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Antioxidant, antimicrobial and cytotoxic properties of Diospyros lotus L. essential oil with supercritical fluid extraction

Pseudomonas aeruginosa: a clinical and genomics update

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