Variability in cell division among anatomical sites shapes Escherichia coli antibiotic survival in a urinary tract infection mouse model DOI Creative Commons
Ariane Amoura,

Claire Pistien,

Camille Chaligné

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 900 - 912.e4

Published: May 16, 2024

Urinary tract infection (UTI), mainly caused by Escherichia coli, are frequent and have a recurrent nature even after antibiotic treatment. Potential bacterial escape mechanisms include growth defects, but probing division in vivo establishing its relation to the response remain challenging. Using synthetic reporter of cell division, we follow temporal dynamics for different E. coli clinical strains UTI mouse model with without antibiotics. We show that more bacteria actively dividing kidneys urine compared bladder. Bacteria survive treatment consistently non-dividing three sites infection. Additionally, demonstrate how both strain vitro persistence profile microenvironment impact dynamics. Understanding relative contribution host environment, heterogeneity, bacteria, is crucial improve therapies infections.

Language: Английский

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

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(8)

Published: July 3, 2023

Language: Английский

Citations

28
Host stress drives tolerance and persistence: The bane of anti-microbial therapeutics DOI Creative Commons
Sophie Hélaine, Brian P. Conlon, Kimberly M. Davis

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 852 - 862

Published: June 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.

Language: Английский

Citations

13
High-throughput fitness experiments reveal specific vulnerabilities of human-adapted Salmonella during stress and infection DOI Creative Commons
Benjamin Wang, Dmitry Leshchiner, Lijuan Luo

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(6), P. 1288 - 1299

Published: June 1, 2024

Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis pathogen evolution. Although genomes numerous isolates with broad variations in host range and human disease manifestations have been sequenced, functional links between phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput genomics on both generalist (Typhimurium) human-restricted (Typhi Paratyphi A) at unprecedented scale study this enteric pathogen. Using a comprehensive systems biology approach, identify gene networks serovar-specific fitness effects across 25 host-associated stresses encountered key stages infection. By experimentally perturbing networks, characterize previously undescribed pseudogenes human-adapted Salmonella. Overall, work highlights specific vulnerabilities encoded within are linked to degradation their genomes, shedding light into evolution

Language: Английский

Citations

11
A growing battlefield in the war against biofilm-induced antimicrobial resistance: insights from reviews on antibiotic resistance DOI Creative Commons
Liu Pai, Sandip Patil,

Sixi Liu

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Dec. 19, 2023

Biofilms are a common survival strategy employed by bacteria in healthcare settings, which enhances their resistance to antimicrobial and biocidal agents making infections difficult treat. Mechanisms of biofilm-induced involve reduced penetration agents, increased expression efflux pumps, altered microbial physiology, genetic changes the bacterial population. Factors contributing formation biofilms include nutrient availability, temperature, pH, surface properties, interactions. Biofilm-associated can have serious consequences for patient outcomes, standard therapies often ineffective against biofilm-associated bacteria, diagnosis treatment challenging. Novel strategies, including antibiotics combination (such as daptomycin vancomycin, colistin azithromycin), biofilm-targeted small molecules (LP3134, LP3145, LP4010, LP1062) target c-di-GMP), immunomodulatory anti-PcrV IgY antibodies Type IIIsecretion system), being developed combat resistance. A multifaceted approach diagnosis, treatment, prevention is necessary address this emerging problem settings.

Language: Английский

Citations

20
Drug tolerance and persistence in bacteria, fungi and cancer cells: Role of non-genetic heterogeneity DOI Creative Commons
Imane El Meouche, Paras Jain, Mohit Kumar Jolly

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 49, P. 102069 - 102069

Published: Aug. 8, 2024

Language: Английский

Citations

6
Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus DOI Creative Commons
Jenna E. Beam, Nikki J. Wagner, Kuan‐Yi Lu

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107942 - 107942

Published: Sept. 17, 2023

is a leading human pathogen that frequently causes relapsing infections. The failure of antibiotics to eradicate infection contributes relapse. Host-pathogen interactions have substantial impact on antibiotic susceptibility and the formation tolerant cells. In this study, we interrogate how major

Language: Английский

Citations

10
Proteomic characterization of persisters in Enterococcus faecium DOI Creative Commons

Charlotte Le Pont,

Benoı̂t Bernay,

Mattéo Gérard

et al.

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 3, 2024

Abstract Background Enterococcus faecium is a Gram-positive bacterium, naturally present in the human intestinal microbiota, but also an opportunistic pathogen responsible for healthcare-associated infections. Persisters are individuals of subpopulation able to survive by arrest growth coping with conditions that lethal rest population. These persistent cells can grow again when stress disappears from their environment and cause relapses. Results In this study, we highlighted ciprofloxacin (10-fold MIC) led formation persister E . The kill curve was typically biphasic initial drop survival (more than 2 orders magnitude reduction) followed constant bacterial count. Growth curves antimicrobial susceptibility tests these persisters were similar those original cells. addition, genomic analyses, confirmed genotypically identical wild type. Comparative proteomic analysis revealed 56 proteins have significantly different abundances compared harvested before addition stressing agent. Most them related energetic metabolisms, some polypeptides involved transcription regulation, seven like CspA, PrsA, ClpX particularly enzymes linked oxidative response. Conclusions This work provided evidences E. enter state may impact chronic infections Moreover, putative key effectors phenotypical behavior identified approach.

Language: Английский

Citations

4
Protozoan predation enhances stress resistance and antibiotic tolerance in Burkholderia cenocepacia by triggering the SOS response DOI Creative Commons
Álvaro Morón,

Alaa E. Tarhouchi,

Iván Belinchón

et al.

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Abstract Bacterivorous protists are thought to serve as training grounds for bacterial pathogens by subjecting them the same hostile conditions that they will encounter in human host. Bacteria survive intracellular digestion exhibit enhanced virulence and stress resistance after successful passage through protozoa but underlying mechanisms unknown. Here we show opportunistic pathogen Burkholderia cenocepacia survives phagocytosis ciliates found domestic hospital sink drains, viable bacteria expelled packaged respirable membrane vesicles with oxidative stress, desiccation, antibiotics, thereby contributing dissemination environment. Reactive oxygen species generated within protozoan phagosome promote formation of persisters tolerant ciprofloxacin activating SOS response. In addition, genes encoding antioxidant enzymes upregulated during increasing radicals. We prove suppression response impairs survival persister protists. This study highlights significance food vacuoles niches foster adaptation natural built environments suggests switch phagosomes may be a widespread phenomenon surviving digestion.

Language: Английский

Citations

4
Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection DOI Creative Commons
Séverin Ronneau, Charlotte Michaux, Rachel T. Giorgio

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1012033 - e1012033

Published: Feb. 29, 2024

The host environment is of critical importance for antibiotic efficacy. By impacting bacterial machineries, stresses encountered by pathogens during infection promote the formation phenotypic variants that are transiently insensitive to action antibiotics. It assumed these recalcitrant bacteria—termed persisters—contribute treatment failure and relapsing infections. Recently, we demonstrated reactive nitrogen species (RNS) protect persisters against β-lactam antibiotics delaying their regrowth within cells. Here, discovered RNS intoxication also collaterally sensitizing them fluoroquinolones infection, explaining higher efficiency intramacrophage Salmonella . reducing respiration proton-motive force, inactivate AcrAB efflux machinery persisters, facilitating accumulation intracellularly. Our work shows target inactivity not sole reason withstand with active being a major contributor survival. Thus, understanding how impacts persister physiology optimize efficacy infection.

Language: Английский

Citations

4
The macrophage–bacterium mismatch in persister formation DOI Creative Commons
Iris Dadole,

Didier Blaha,

Nicolas Personnic

et al.

Trends in Microbiology, Journal Year: 2024, Volume and Issue: 32(10), P. 944 - 956

Published: March 4, 2024

Many pathogens are hard to eradicate, even in the absence of genetically detectable antimicrobial resistance mechanisms and despite proven antibiotic susceptibility. The fraction clonal bacteria that temporarily elude effective treatments is commonly known as 'antibiotic persisters.' Over past decade, there has been a growing body research highlighting pivotal role played by cellular host development persisters. In parallel, this also sought elucidate molecular underlying formation intracellular persisters demonstrated prominent for bacterial stress response. However, questions remain regarding conditions leading stress-induced among population an ostensibly uniform environment. opinion, following brief review current state knowledge persisters, we explore ways which macrophage functional heterogeneity phenotypic may contribute emergence these We propose degree mismatch between permissiveness preparedness invade thrive intracellularly explain nonreplicating

Language: Английский

Citations

4