Dual-acting hybrid antibiotics: a promising strategy to combat bacterial resistance

2010 ◽  
Vol 5 (9) ◽  
pp. 883-902 ◽  
Author(s):  
Varvara Pokrovskaya ◽  
Timor Baasov
Keyword(s):  
Bacterial Resistance ◽  
Promising Strategy ◽  
Hybrid Antibiotics

scholarly journals Can Vitamin B12 Assist the Internalization of Antisense LNA Oligonucleotides into Bacteria?

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 379
Author(s):  
Sara Pereira ◽  
Ruwei Yao ◽  
Mariana Gomes ◽  
Per Trolle Jørgensen ◽  
Jesper Wengel ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Antisense Oligonucleotides ◽  
Bacterial Resistance ◽  
Intracellular Localization ◽  
Innovative Strategies ◽  
E Coli ◽  
Promising Strategy ◽  
Bacterial Growth Inhibition ◽  
Bacterial Genes

The emergence of bacterial resistance to traditional small-molecule antibiotics is fueling the search for innovative strategies to treat infections. Inhibiting the expression of essential bacterial genes using antisense oligonucleotides (ASOs), particularly composed of nucleic acid mimics (NAMs), has emerged as a promising strategy. However, their efficiency depends on their association with vectors that can translocate the bacterial envelope. Vitamin B12 is among the largest molecules known to be taken up by bacteria and has very recently started to gain interest as a trojan-horse vector. Gapmers and steric blockers were evaluated as ASOs against Escherichia coli (E. coli). Both ASOs were successfully conjugated to B12 by copper-free azide-alkyne click-chemistry. The biological effect of the two conjugates was evaluated together with their intracellular localization in E. coli. Although not only B12 but also both B12-ASO conjugates interacted strongly with E. coli, they were mostly colocalized with the outer membrane. Only 6–9% were detected in the cytosol, which showed to be insufficient for bacterial growth inhibition. These results suggest that the internalization of B12-ASO conjugates is strongly affected by the low uptake rate of the B12 in E. coli and that further studies are needed before considering this strategy against biofilms in vivo.

Covalently linked kanamycin – Ciprofloxacin hybrid antibiotics as a tool to fight bacterial resistance

2017 ◽  
Vol 25 (11) ◽  
pp. 2917-2925 ◽  
Author(s):  
Michal Shavit ◽  
Varvara Pokrovskaya ◽  
Valery Belakhov ◽  
Timor Baasov
Keyword(s):  
Bacterial Resistance ◽  
Covalently Linked ◽  
Hybrid Antibiotics

scholarly journals Thiol and Disulfide Containing Vancomycin Derivatives Against Bacterial Resistance and Biofilm Formation

2021 ◽  
Author(s):  
Inga S. Shchelik ◽  
Karl Gademann
Keyword(s):  
Biofilm Formation ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Promising Strategy ◽  
Vancomycin Resistant ◽  
New Compounds ◽  
Sulfur Containing

Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. The last resort antibiotic vancomycin is under threat, due to the increasing appearance of vancomycin resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol- and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin resistant microbes and Gram-negative bacteria. Moreover, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB resistant Enterococcus compared to vancomycin. This work established a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on structural optimization of antibiotics with sulfur-containing modifications.

Mentoring: A Promising Strategy for Youth Development

2001 ◽  
Author(s):  
Susan M. Jekielek ◽  
Kristin M. Moore ◽  
Elizabeth C. Hair ◽  
Harriet J. Scarupa
Keyword(s):  
Youth Development ◽  
Promising Strategy

Isotopically Labeled Desthiobiotin Azide (isoDTB) Tags Enable Global Profiling of the Bacterial Cysteinome

2019 ◽  
Author(s):  
Patrick R. A. Zanon ◽  
Lisa Lewald ◽  
Stephan M. Hacker
Keyword(s):  
Binding Sites ◽  
Bacterial Resistance ◽  
Mevalonate Pathway ◽  
Rapid Development ◽  
High Reactivity ◽  
Functional Importance ◽  
Essential Proteins ◽  
Covalent Inhibitors ◽  
Druggable Targets ◽  
Covalent Ligands

Rapid development of bacterial resistance has led to an urgent need to find new druggable targets for antibiotics. In this context, residue-specific chemoproteomic approaches enable proteome-wide identification of binding sites for covalent inhibitors. Here, we describe isotopically labeled desthiobiotin azide (isoDTB) tags that are easily synthesized, shorten the chemoproteomic workflow and allow an increased coverage of cysteines in bacterial systems. We quantify 59% of all cysteines in essential proteins in <i>Staphylococcus aureus</i> and discover 88 cysteines with high reactivity, which correlates with functional importance. Furthermore, we identify 268 cysteines that are engaged by covalent ligands. We verify inhibition of HMG-CoA synthase, which will allow addressing the bacterial mevalonate pathway through a new target. Overall, a comprehensive map of the bacterial cysteinome is obtained, which will facilitate the development of antibiotics with novel modes-of-action.

Political Inclusion Reduces Political Prejudice

2019 ◽  
Author(s):  
Jan G. Voelkel ◽  
Dongning Ren ◽  
Mark John Brandt
Keyword(s):  
The Political ◽  
Political Discussion ◽  
Total N ◽  
Cohen’S D ◽  
Promising Strategy ◽  
Political Inclusion ◽  
Cohen's D ◽  
Political Divide ◽  
Scenario Study ◽  
Fair Chance

The political divide is characterized by liberals and conservatives who hold strong prejudice against each other. Here we introduce one possible strategy for reducing political prejudice: political inclusion. We define political inclusion as receiving a fair chance to voice one’s opinions in a discussion of political topics with political outgroup members. This strategy may reduce political prejudice by inducing perceptions of the political outgroup as fair and respectful; however, such a strategy may also highlight conflicting attitudes and worldviews, thereby further exacerbating prejudice. In three preregistered studies (total N = 799), we test if political inclusion reduces or increases prejudice toward the political outgroup. Specifically, political inclusion was manipulated with either an imagined scenario (Study 1) or a concurrent experience in an ostensible online political discussion (Studies 2 &amp; 3). Across all studies, participants who were politically included by political outgroup members reported reduced prejudice toward their outgroup compared to participants in a neutral control condition (Cohen’s d [-0.27, -0.50]). This effect was mediated by perceptions of the political outgroup as fairer and less dissimilar in their worldviews. Our results indicate that political discussions that are politically inclusive do not cause additional prejudice via worldview conflict, but instead give others a feeling of being heard. It is a promising strategy to reduce political prejudice.

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