Csaba Pal Laboratory

Study uncovers the core principles of low-resistance antibiotics A study published in Nature Communications has revealed novel insights into bacterial resistance and offers a promising strategy for developing antibiotics that minimize the evolution of resistance.

A dual-target antibiotic strategy, combining membrane disruption with another cellular pathway, shows promise in reducing bacterial resistance, offering a new direction in combating antimicrobial resistance. doi.org/g855sh

We are looking for a postdoc in #EvolutionarySystemsBiology.
Exciting science, amazing team, wonderful city!
landrylab.ibis.ulaval.ca/research-opp...
#evolution #synbio #systemsbiology #genomics

For previous research on #FutureAntibiotics and resistance development see our recent publications here: tinyurl.com/2cbyrx55 and tinyurl.com/2mxaz5a6 #MEvoSky

5/5 - Contributors:
This work was spearheaded by @m-elvin.bsky.social and @marczikkely.bsky.social at HUN-REN Biological Research Centre, Szeged

4/5 - Implications for the Future:
These insights provide a blueprint for developing next-gen antibiotics ( #FutureAntibiotics) designed to stay one step ahead of bacterial defenses. It’s a promising direction in the fight against #AntibioticResistance #AMR.

3/5 - A stark contrast:
Dual-target topoisomerase antibiotics, despite having two intracellular targets, were more prone to resistance. This highlights that which targets matter just as much as how many. #DrugDevelopment

2/5 – Dual target permeabilizers:
We tested three promising #DrugCandidates – POL7306, Tridecaptin M152-P3, and SCH79797 – against tough #ESKAPE pathogens like E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. The results? #ResistanceEvolution was significantly limited.

1/5 - The strategy:
By combining membrane disruption with another key cellular pathway, we can dramatically limit bacterial #resistance. This “double whammy” makes it much harder for bacteria to fight back. #RationalDesign #Antibiotics

Exploring the principles behind antibiotics with limited resistance - Nature Communications This study shows that only those dual-targeting antibiotics limit resistance in Gram-negative pathogens that also target the membrane of the bacteria. This mechanism provides a basis for designing fut...

🚨 Our latest research in @naturecomms.bsky.social shows a promising strategy for less resistance-prone #antibiotics. For details, see the thread below and read the paper “Exploring the principles behind antibiotics with limited resistance” here: #MEvoSky www.nature.com/articles/s41...

New antibiotics can develop resistance before even hitting the market Researchers from the HUN-REN Biological Research Centre, Szeged (Hungary), have made a concerning discovery about the future of antibiotics.

Two recent studies led by 🇭🇺 @csabapallab.bsky.social find that resistance can develop against new 💊 antibiotics even before they are widely used, compromising their effectiveness from the start. #antibioticresistance #AMR

Alternative drug modalities/approaches are desperately needed to supplement the pipeline of antibiotics.

ESKAPE pathogens are outsmarting us. Our latest paper in @naturemicrobiol.bsky.social reveals alarming ease of resistance evolution to antibiotics in development. Collaborative work with @csabapallab.bsky.social‬
and Kintses Lab

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro - Nature Microbiology An extensive experimental analysis of resistance to antibiotics in development or introduced post-2017 in ESKAPE bacteria reveals the dynamics of resistance acquisition, mutational targets and the pre...

💊🦠OUT NOW - comprehensive analysis of the propensity of ESKAPE pathogens to evolve resistance to new and in development antibiotics by Csaba Pal, Balint Kintses, Balazs Papp and colleagues. Dive in here...
www.nature.com/articles/s41...

For a similar study on Gram-positive bacteria, check out our previous thread: bsky.app/profile/csab...

7/7 🔗 This study spearheaded by @lejladaruka.bsky.social, @marczikkely.bsky.social, @petraszili.bsky.social and @zoltanfarkas81.bsky.social at Biological Research Centre, Szeged. Important contributions from our long-term collaborators @balazs-papp-lab.bsky.social and Balint Kintses Lab.

6/7 📢 Stay tuned! Our upcoming study will reveal a promising strategy to develop less resistance-prone antibiotics! #DrugDevelopment

5/7 🔬 The study suggests that certain bacteria were less prone to develop resistance against some of the tested antibiotics, highlighting the potential in narrow-spectrum therapeutics. This presents hope for more effective future treatments. #Antibiotics #PublicHealth

4/7 🌍 Functional metagenomics revealed that mobile resistance genes exist not only in clinical isolates but also in the soil and even the human gut microbiome. Resistance is EVERYWHERE, making it harder to tackle with new treatments. #GlobalHealth

3/7 🧬 Even more worrying: resistance mutations were already present in natural bacterial populations. This means that some bacteria may already have the arsenal to resist future antibiotics they have never encountered. #EvolutionOfResistance

2/7 🦠 We tested 13 new antibiotics (some on the market for a couple of years, others still in development) against 4 of the most critical Gram-negative pathogens. The result? Resistance emerged in just 60 days. This shows how quickly bacteria can adapt! #AntibioticResistance

1/7 The rise of drug-resistant infections is a global crisis, but many pharma companies have abandoned antibiotic R&D. While some new drugs are in development, our study shows resistance is emerging rapidly, even to these #FutureAntibiotics. Let’s unpack the results.⬇️

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro - Nature Microbiology An extensive experimental analysis of resistance to antibiotics in development or introduced post-2017 in ESKAPE bacteria reveals the dynamics of resistance acquisition, mutational targets and the pre...

🚨 Excited to share that our new study, “ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro” is published in @naturemicrobiol.bsky.social. For details, see the 🧵below and read the paper here: www.nature.com/articles/s41...

Awesome! Many thanks ‪@thealexknapp.bsky.social‬ for spotlighting our recent work!

Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance Antibiotic candidates induce multidrug resistance in Staphylococcus aureus without compromising bacterial viability.

Thrilled to share our latest work, "Antibiotic candidates for Gram-positive bacterial infections induce multidrug resistance" in Science Translational Medicine! For details, see the thread below and read the paper here: www.science.org/doi/10.1126/...

This work was spearheaded by Ana Martins, Fanni Judak and @zoltanfarkas81.bsky.social at Biological Research Centre, Szeged. Stay tuned for upcoming updates on #FutureAntibiotics - some exciting stuff on the horizon.

Based on our findings, early drug development must prioritize understanding resistance evolution at early stages. Additionally, R&D should focus on creating drug compounds with truly novel designs that actively minimize resistance development. 6/6

Key lab-observed resistance mutations already exist in natural bacterial populations. Decades of traditional antibiotic use might have selected for these variants, undermining the long-term efficacy of new drugs even before market introduction. #DrugDevelopment 5/n

We discovered overlapping resistance mechanisms: mutations in regulatory systems linked teixobactin resistance to patterns seen with vancomycin and daptomycin. This underscores the interconnected evolution of resistance, complicating efforts to combat #AMR. 4/n

Resistant S. aureus strains also developed multi-drug resistance to #teixobactin & stayed virulent in an invertebrate infection model. These bacteria could thrive clinically - alarming for future #therapies. 3/n

With the exception of a repurposed drug (SCH79797), S. aureus rapidly developed #resistance to promising candidates, even showing cross-resistance to antibiotics already in clinical use. This complicates treatment strategies. 2/n