Antibiotics change the population growth rate heterogeneity and morphology of bacteria DOI Creative Commons
Morten Kals, Emma Kals, Jurij Kotar

и другие.

PLoS Pathogens, Год журнала: 2025, Номер 21(2), С. e1012924 - e1012924

Опубликована: Фев. 5, 2025

A better understanding of the system-level effects antibiotics on bacterial cells is essential to address growing challenge antibiotic resistance. Utilising Multipad Agarose Plate (MAP) platforms, we monitor growth rate and cell morphology three clinically relevant species ( E.coli , S.aureus P.aeruginosa ) following exposure 14 across 11 concentrations (31 microbe-antibiotic combinations in total). Our results reveal a consistent increase population heterogeneity (PGRH) as drug approach minimum inhibitory concentration (MIC). Strikingly, magnitude this correlates with functional distance between ribosome specific cellular processes targeted by antibiotics. Among seven classes studied, protein synthesis inhibitors disruptors cause lowest PGRH, while progressively increases RNA inhibitors, DNA replication membrane wall inhibitors. Because central control, hypothesize that might arise at system level result propagation damage synthesis. Low desirable from clinical perspective, high often associated persistence treatment survival. Additionally, observed strong correlation morphological alterations inhibition all tested. This led development novel parameter, MOR 50 which enables rapid estimation MIC for susceptibility testing (AST) single snapshot after just 2.5 hours incubation. In addition introducing novel, resource-efficient AST method, our findings shed new light perturbations bacteria, inform design.

Язык: Английский

Inhibitors of bacterial H 2 S biogenesis targeting antibiotic resistance and tolerance DOI
Konstantin Shatalin, Ashok Nuthanakanti, A. Kaushik

и другие.

Science, Год журнала: 2021, Номер 372(6547), С. 1169 - 1175

Опубликована: Июнь 10, 2021

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as primary generator H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, discovered small molecules that inhibit CSE. These inhibitors potentiate bactericidal against both pathogens vitro mouse models infection. CSE also suppress tolerance, disrupting biofilm formation substantially reducing number persister bacteria survive antibiotic treatment. Our results establish a multifunctional factor drug target versatile enhancers.

Язык: Английский

Процитировано

182
Bacterial persisters are a stochastically formed subpopulation of low-energy cells DOI Creative Commons

Sylvie Manuse,

Yue Shan, Silvia J. Cañas-Duarte

и другие.

PLoS Biology, Год журнала: 2021, Номер 19(4), С. e3001194 - e3001194

Опубликована: Апрель 19, 2021

Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance chronic infections antibiotic therapy, mechanism formation has remained elusive. We show sorted Escherichia coli with low levels energy-generating enzymes better able survive killing. Using microfluidics time-lapse microscopy and fluorescent reporter for vivo ATP measurements, we find level survives ampicillin. propose these formed stochastically as result fluctuations abundance components. These findings point general “low energy” persister formation.

Язык: Английский

Процитировано

130
Composition and liquid-to-solid maturation of protein aggregates contribute to bacterial dormancy development and recovery DOI Creative Commons
Celien Bollen, Sofie Louwagie,

Femke Deroover

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 26, 2025

Recalcitrant bacterial infections can be caused by various types of dormant bacteria, including persisters and viable but nonculturable (VBNC) cells. Despite their clinical importance, we know fairly little about dormancy development recovery. Previously, established a correlation between protein aggregation in Escherichia coli. Here, present further support for direct relationship both. Our experiments demonstrate that aggregates progressively sequester proteins involved energy production, thereby likely causing ATP depletion dormancy. Furthermore, structural features determine the cell's ability to exit resume growth. Proteins were shown first assemble liquid-like condensates solidify over time. This liquid-to-solid phase transition impedes aggregate dissolution, preventing growth resumption. data model which structure, rather than cellular activity, marks from persister VBNC state. are often authors explore how composition structure affect this

Язык: Английский

Процитировано

3
Antimicrobial and Antibiofilm Activity of prepared Thymol@UIO-66 and Thymol/ZnONPs@UIO-66 Nanoparticles against Methicillin-resistant Staphylococcus aureus: A Synergistic Approach DOI

Alireza Eskandari,

Seyedeh Nooshin Safavi,

Hamidreza Sahrayi

и другие.

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер 249, С. 114529 - 114529

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

2
Formation mechanisms of viable but nonculturable bacteria through induction by light-based disinfection and their antibiotic resistance gene transfer risk: A review DOI
Yiwei Cai, Jianying Liu, Guiying Li

и другие.

Critical Reviews in Environmental Science and Technology, Год журнала: 2021, Номер 52(20), С. 3651 - 3688

Опубликована: Июнь 4, 2021

Disinfection technologies, especially light-based disinfection, have undergone tremendous development and innovation, but this treatment can cause bacteria to enter viable nonculturable (VBNC) state. Due their strong tolerance, VBNC cannot be completely removed by disinfection thereby posing a potential risk for antibiotic resistance gene (ARG) transfer. Therefore, better understand interpret transfer of ARGs, article systematically reviewed changes in morphology, physiology virulence after entering In addition, quantitative detection methods bacteria, such as cell membrane integrity-mediated LIVE/DEAD Baclight assay, qPCR-based assays, phage-based methods, concluding that there is still lack in-situ real-time bacteria. Health risks environmental application value were then valuated, with data indicating great the domain microbial utilization. Furthermore, induction conditions (especially disinfection) formation mechanisms highlighted. Formation mainly involve stringent response, general stress response system toxin-antitoxin (TA) system. Moreover, horizontal (HGT) ARGs during induced was evaluated. It found may transferred through conjugation, transformation transduction. Finally, current deficiencies future challenges those influenced summarized. This review provides new insights into mechanisms, applications ARG

Язык: Английский

Процитировано

70
Nucleotide biosynthesis: the base of bacterial pathogenesis DOI
Mariya I. Goncheva,

Denny Chin,

David E. Heinrichs

и другие.

Trends in Microbiology, Год журнала: 2022, Номер 30(8), С. 793 - 804

Опубликована: Янв. 21, 2022

Язык: Английский

Процитировано

69
Host Cell Oxidative Stress Induces Dormant Staphylococcus aureus Persisters DOI
Frédéric Peyrusson, Tiep Khac Nguyen,

Tomé Najdovski

и другие.

Microbiology Spectrum, Год журнала: 2022, Номер 10(1)

Опубликована: Фев. 23, 2022

By their capacity to survive antibiotic pressure and regrow give rise a susceptible population once this is relieved, intracellular persisters of S. aureus may contribute explain therapeutic failures recurrent infections. Here, we show that the level dormancy subsequent resuscitate from resting state are dependent on oxidative stress in host cells where bacteria survive.

Язык: Английский

Процитировано

50
Environmental, mechanistic and evolutionary landscape of antibiotic persistence DOI
Celien Bollen, Elen Louwagie, Natalie Verstraeten

и другие.

EMBO Reports, Год журнала: 2023, Номер 24(8)

Опубликована: Июль 3, 2023

Язык: Английский

Процитировано

27
Decline in nitrosative stress drives antibiotic persister regrowth during infection DOI Creative Commons
Séverin Ronneau, Charlotte Michaux, Sophie Hélaine

и другие.

Cell Host & Microbe, Год журнала: 2023, Номер 31(6), С. 993 - 1006.e6

Опубликована: Май 25, 2023

Язык: Английский

Процитировано

25
Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics DOI Creative Commons
Sophie Hélaine, Brian P. Conlon, Kimberly M. Davis

и другие.

Cell Host & Microbe, Год журнала: 2024, Номер 32(6), С. 852 - 862

Опубликована: Июнь 1, 2024

Antibiotic resistance, typically associated with genetic changes within a bacterial population, is frequent contributor to antibiotic treatment failures. persistence and tolerance, which we collectively term recalcitrance, represent transient phenotypic in the population that prolong survival presence of lethal concentrations antibiotics. recalcitrance challenging detect investigate-traditionally studied under vitro conditions, our understanding during infection its contribution failure limited. Recently, significant progress has been made study antibiotic-recalcitrant populations pathogenic species, including Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica, Yersiniae, context host environment. Despite diversity these pathogens models, shared signals responses promote common features vulnerabilities persisters tolerant bacteria have emerged. These will be discussed here, along toward developing therapeutic interventions better treat recalcitrant pathogens.

Язык: Английский

Процитировано

13