Systematic mapping of antibiotic cross-resistance and collateral sensitivity with chemical genetics DOI Creative Commons
Nazgul Sakenova, Elisabetta Cacace, Askarbek Orakov

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Abstract By acquiring or evolving resistance to one antibiotic, bacteria can become cross-resistant a second which further limits therapeutic choices. In the opposite scenario, initial leads collateral sensitivity inform cycling combinatorial treatments. Despite their clinical relevance, our knowledge of both interactions is limited. We used published chemical genetics data Escherichia coli single-gene deletion library in 40 antibiotics and devised metric that discriminates between known cross-resistance collateral-sensitivity antibiotic interactions. Thereby we inferred 404 cases 267 collateral-sensitivity, expanding number by over threefold. validated 64/70 using experimental evolution. identifying mutants driving these genetics, demonstrated drug pair exhibit depending on mechanism. Finally, applied collateral-sensitive pairs combination reduce antibiotic-resistance development vitro.

Language: Английский

Translating eco-evolutionary biology into therapy to tackle antibiotic resistance DOI
Fernando Sanz‐García, Teresa Gil‐Gil, Pablo Laborda

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(10), P. 671 - 685

Published: May 19, 2023

Language: Английский

Citations

45
Self‐assembly multifunctional DNA tetrahedron for efficient elimination of antibiotic‐resistant bacteria DOI Creative Commons
Tiantian Wu, Yu Fu, Shuang Guo

et al.

Aggregate, Journal Year: 2023, Volume and Issue: 5(1)

Published: Aug. 7, 2023

Abstract Antibiotic resistance is a major challenge in the clinical treatment of bacterial infectious diseases. Herein, we constructed multifunctional DNA nanoplatform as versatile carrier for bacteria‐specific delivery antibiotic ciprofloxacin (CIP) and classic nanoantibiotic silver nanoparticles (AgNP). In our rational design, CIP was efficiently loaded self‐assembly double‐bundle tetrahedron through intercalation with duplex, single‐strand DNA‐modified AgNP embedded cavity hybridization. With site‐specific assembly targeting aptamer well‐defined tetrahedron, dual‐antibiotic system exhibited excellent combined bactericidal properties. enhanced accumulation breaking out membrane bacteria, effectively inhibited biofilm formation promoted healing infected wounds vivo. This DNA‐based provides promising strategy antibiotic‐resistant infections.

Language: Английский

Citations

38
Tackling antibiotic resistance by inducing transient and robust collateral sensitivity DOI Creative Commons
Sara Hernando‐Amado, Pablo Laborda, José Luis Martínez

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 30, 2023

Abstract Collateral sensitivity (CS) is an evolutionary trade-off traditionally linked to the mutational acquisition of antibiotic resistance (AR). However, AR can be temporally induced, and possibility that this causes transient, non-inherited CS, has not been addressed. Mutational ciprofloxacin leads robust CS tobramycin in pre-existing antibiotic-resistant mutants Pseudomonas aeruginosa . Further, strength phenotype higher when nfxB mutants, over-producing efflux pump MexCD-OprJ, are selected. Here, we induce transient -mediated by using antiseptic dequalinium chloride. Notably, induction renders analyzed clinical isolates, including tobramycin-resistant isolates. combining with chloride drive these strains extinction. Our results support could allow design new strategies tackle infections, avoiding mutations on which inherited depends.

Language: Английский

Citations

28
The role of hypermutation and collateral sensitivity in antimicrobial resistance diversity of Pseudomonas aeruginosa populations in cystic fibrosis lung infection DOI Creative Commons
Jelly Vanderwoude, Sheyda Azimi, Timothy D. Read

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(2)

Published: Jan. 3, 2024

Pseudomonas aeruginosa is an opportunistic pathogen which causes chronic, drug-resistant lung infections in cystic fibrosis (CF) patients. In this study, we explore the role of genomic diversification and evolutionary trade-offs antimicrobial resistance (AMR) diversity within P. populations sourced from CF infections. We analyzed 300 clinical isolates four patients (75 per patient) found that not a consistent indicator phenotypic AMR diversity. Remarkably, some genetically less diverse showed comparable to those with significantly more genetic variation. also observed hypermutator strains frequently exhibited increased sensitivity antimicrobials, contradicting expectations their treatment histories. Investigating potential trade-offs, no substantial evidence collateral among aminoglycoside, beta-lactam, or fluoroquinolone antibiotics, nor did observe between growth conditions mimicking sputum. Our findings suggest (i) prerequisite for diversity, (ii) may develop under selection pressure, (iii) prominent feature strains, (iv) single antibiotic does necessarily lead significant fitness costs. These insights challenge prevailing assumptions about evolution chronic infections, emphasizing complexity bacterial adaptation during infection.IMPORTANCEUpon infection lung, rapidly acquires mutations, especially genes involved (AMR), often resulting diverse, treatment-resistant populations. However, population context still poorly understood. undergoing tobramycin evolved relative non-hypermutators same population. This finding suggests only exert weak pressure on lung. further these populations, suggesting be robust, naturally occurring phenomenon microbe.

Language: Английский

Citations

11
Bacterial Subcellular Architecture, Structural Epistasis, and Antibiotic Resistance DOI Creative Commons
Fernando Baquero, José Luis Martínez,

Álvaro Sánchez

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(5), P. 640 - 640

Published: April 23, 2023

Epistasis refers to the way in which genetic interactions between some loci affect phenotypes and fitness. In this study, we propose concept of "structural epistasis" emphasize role variable physical molecules located particular spaces inside bacterial cell emergence novel phenotypes. The architecture (typically Gram-negative), consists concentrical layers membranes, particles, with differing configurations densities (from outer membrane nucleoid) determines is turn determined by shape size, depending on growth phases, exposure toxic conditions, stress responses, environment. Antibiotics change cell's internal molecular topology, producing unexpected among molecules. contrast, changes size may alter antibiotic action. mechanisms resistance (and their vectors, as mobile elements) also influence connectivity can produce phenotypes, influencing action other antimicrobial agents.

Language: Английский

Citations

15
Recent advances in nanoantibiotics against multidrug-resistant bacteria DOI Creative Commons

Mulan Li,

Ying Liu,

Youhuan Gong

et al.

Nanoscale Advances, Journal Year: 2023, Volume and Issue: 5(23), P. 6278 - 6317

Published: Jan. 1, 2023

Multidrug-resistant (MDR) bacteria-caused infections have been a major threat to human health. The abuse of conventional antibiotics accelerates the generation MDR bacteria and makes situation worse. emergence nanomaterials holds great promise for solving this tricky problem due their multiple antibacterial mechanisms, tunable spectra, low probabilities inducing drug resistance. In review, we summarize mechanism resistance, introduce recently developed dealing with

Language: Английский

Citations

15
Evolution of Habitat-Dependent Antibiotic Resistance in Pseudomonas aeruginosa DOI Creative Commons
Pablo Laborda, José Luis Martínez, Sara Hernando‐Amado

et al.

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(4)

Published: June 29, 2022

Predicting evolution toward antibiotic resistance (AR) and its associated trade-offs, such as collateral sensitivity, is important to design evolution-based strategies tackle AR. However, the effect of nutrients' availability on evolution, particularly those that can be found under in vivo infection conditions, has been barely addressed.

Language: Английский

Citations

21
Epistasis decreases with increasing antibiotic pressure but not temperature DOI Creative Commons
Ana‐Hermina Ghenu, André Amado, Isabel Gordo

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2023, Volume and Issue: 378(1877)

Published: April 2, 2023

Predicting mutational effects is essential for the control of antibiotic resistance (ABR). Predictions are difficult when there strong genotype-by-environment (G × E), gene-by-gene G or epistatic) gene-by-gene-by-environment E) interactions. We quantified E in Escherichia coli across environmental gradients. created intergenic fitness landscapes using gene knock-outs and single-nucleotide ABR mutations previously identified to vary extent our environments interest. Then, we measured competitive a complete combinatorial set temperature dosage In this way, assessed predictability 15 12 different but related environments. found interactions rugged absence antibiotic, as concentration increased, genotypes quickly overshadowed those knock-outs, became smoother. Our work reiterates that some single mutants, like conferring susceptibility antibiotics, have consistent genetic backgrounds stressful Thus, although epistasis may reduce evolution benign environments, be more predictable adverse This article part theme issue 'Interdisciplinary approaches predicting evolutionary biology'.

Language: Английский

Citations

12
Preserving the efficacy of antibiotics to tackle antibiotic resistance DOI Creative Commons
Pablo Laborda, Teresa Gil‐Gil, José Luis Martínez

et al.

Microbial Biotechnology, Journal Year: 2024, Volume and Issue: 17(7)

Published: July 1, 2024

Different international agencies recognize that antibiotic resistance is one of the most severe human health problems humankind facing. Traditionally, introduction new antibiotics solved this problem but various scientific and economic reasons have led to a shortage novel at pipeline. This situation makes mandatory implementation approaches preserve efficacy current antibiotics. The concept not novel, only action taken for such preservation had been 'prudent' use antibiotics, trying reduce selection pressure by reducing amount However, even if are used when needed, will be insufficient because inescapable outcome antibiotics' use. A deeper understanding alterations in bacterial physiology upon acquisition during infection help design improved strategies treat infections. In article, we discuss interconnection between (and activity) metabolism, particularly vivo, bacteria causing infection. We as well how evolutionary trade-offs, collateral sensitivity, associated with may define evolution-based therapeutic fight currently

Language: Английский

Citations

4
Drug combinations targeting antibiotic resistance DOI Creative Commons
Bence Bognár, Réka Spohn, Viktória Lázár

et al.

npj Antimicrobials and Resistance, Journal Year: 2024, Volume and Issue: 2(1)

Published: Oct. 3, 2024

Language: Английский

Citations

4