A5027456587- Antibiotic Resistance in Bacteria
- Cancer therapeutics and mechanisms
- Evolution and Genetic Dynamics
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Neutropenia and Cancer Infections
- Gut microbiota and health
- Antimicrobial Peptides and Activities
- Bioactive Compounds and Antitumor Agents
- Bacterial Genetics and Biotechnology
- Antibiotic Use and Resistance
- Vibrio bacteria research studies
- Biochemical and Molecular Research
- Malaria Research and Control
- Synthesis and biological activity
- Genomics and Phylogenetic Studies
- Tuberculosis Research and Epidemiology
- Escherichia coli research studies
Institute of Biochemistry
2018-2025
HUN-REN Szegedi Biológiai Kutatóközpont
2018-2025
University of Szeged
2023-2025
Hungarian Academy of Sciences
2018-2024
Research Network (United States)
2023
Hungarian Research Network
2022-2023
Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence to 13 introduced after 2017 or currently compared with in-use antibiotics. Laboratory showed that clinically relevant arises within 60 days exposure Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens. Resistance mutations are already present natural populations...
Significance Bacterial recombineering allows researchers to interrogate microbes by modifying their genomic DNA. Improvements the efficiency of have allowed many simultaneous edits be made at once. Here we describe "serial enrichment for efficient recombineering" (SEER), a method identifying single-stranded DNA-annealing proteins (SSAPs) in microbe interest. We use SEER identify two SSAPs: 1) CspRecT doubles editing over Redβ, state-of-the-art Escherichia coli recombineering; and 2) PapRecT...
A new series of dual low nanomolar benzothiazole inhibitors bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, faecium multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] the Gram-negatives Acinetobacter baumannii Klebsiella pneumoniae (best MICs: 1–4 μg/mL). Lead 7a was...
Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that evolution of therapeutic AMPs may generate cross-resistance host AMPs, compromising cornerstone innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin (MCR) has been selected by use in agriculture and medicine. Here, we show MCR provides selective advantage Escherichia coli presence key from humans...
Abstract Antibiotics that target multiple cellular functions are anticipated to be less prone bacterial resistance. Here we hypothesize while dual targeting is crucial, it not sufficient in preventing Only those antibiotics simultaneously membrane integrity and block another pathway display reduced resistance development. To test the hypothesis, focus on three antibiotic candidates, POL7306, Tridecaptin M152-P3 SCH79797, all of which fulfill above criteria. show evolution against these...
Multitargeting antibiotics, i.e., single compounds capable of inhibiting two or more bacterial targets, are generally considered to be a promising therapeutic strategy against resistance evolution. The rationale for this theory is that multitargeting antibiotics demand the simultaneous acquisition multiple mutations at their respective target genes achieve significant resistance. presumes individual provide little no benefit host.
Several antibiotic candidates are in development against Gram-positive bacterial pathogens, but their long-term utility is unclear. To investigate this issue, we studied the laboratory evolution of resistance to antibiotics that have not yet reached market. We found that, with exception compound SCH79797, generally readily evolves Staphylococcus aureus . Cross-resistance was detected between such and currently clinical use, including vancomycin, daptomycin, promising candidate teixobactin....
We present a new series of 2-aminobenzothiazole-based DNA gyrase B inhibitors with promising activity against ESKAPE bacterial pathogens. Based on the binding information extracted from cocrystal structure inhibitor A, in complex Escherichia coli GyrB24, we expanded chemical space benzothiazole-based to C5 position benzothiazole ring. In particular, compound E showed low nanomolar inhibition (IC50 < 10 nM) and broad-spectrum antibacterial pathogens belonging group, minimum inhibitory...
In this work, we describe an improved series of N-phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective high-priority gram-positive bacteria. The most compounds show low nanomolar IC50 values Escherichia coli gyrase, in addition, compound 7c also inhibits E. topoisomerase IV the concentration range, making it a promising candidate for development dual these enzymes. All tested high selectivity towards human isoform IIα. Compounds 6a, 6d, 6e 6f...
Abstract Despite the ongoing development of new antibiotics, future evolution bacterial resistance may render them ineffective. We demonstrate that antibiotic candidates currently under are as prone to in Gram-negative pathogens clinically employed antibiotics. Resistance generally stems from both genomic mutations and transfer genes microbiomes associated with humans, factors carrying equal significance. The molecular mechanisms overlap those found commonly used Therefore, these already...
Abstract Exploiting bacteriophage-derived homologous recombination processes has enabled precise, multiplex editing of microbial genomes and the construction billions customized genetic variants in a single day. The techniques that enable this, Multiplex Automated Genome Engineering (MAGE) directed evolution with random genomic mutations (DIvERGE), are however currently limited to handful microorganisms for which single-stranded DNA-annealing proteins (SSAPs) promote efficient recombineering...
Multi-targeting antibiotics, i.e. single compounds capable to inhibit two or more bacterial targets offer a promising therapeutic strategy, but information on resistance evolution against such drugs is scarce. Gepotidacin an antibiotic candidate that selectively inhibits both DNA gyrase and topoisomerase IV. In susceptible organism, Klebsiella pneumoniae , combination of specific mutations in these target proteins provide over 2000-fold increment resistance, while individually none affect...
Abstract Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that evolution of therapeutic AMPs may generate cross-resistance host AMPs, compromising cornerstone innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin (MCR) has been selected by use in agriculture and medicine. Here we show MCR provides selective advantage E. coli presence key from humans...