Protozoan predation enhances stress resistance and antibiotic tolerance in the opportunistic pathogenBurkholderia cenocepaciaby triggering the SOS response DOI Creative Commons
Álvaro Morón,

Iván Belinchón,

Alaa E. Tarhouchi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 24, 2023

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 remain be clarified. 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. By using diverse methodological approaches, demonstrate reactive oxygen species generated within protozoan phagosome promote formation of persisters tolerant ciprofloxacin activating SOS response. Besides, 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 a widespread phenomenon surviving digestion.

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
Amoebae as training grounds for microbial pathogens DOI Creative Commons

Christopher T. D. Price,

Hannah E. Hanford,

Tasneem Al‐Quadan

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: July 8, 2024

Grazing of amoebae on microorganisms represents one the oldest predator-prey dynamic relationships in nature. It a genetic "melting pot" for an ancient and continuous multi-directional inter- intra-kingdom horizontal gene transfer between its preys, intracellular microbial residents, endosymbionts, giant viruses, which has shaped evolution, selection, adaptation microbes that evade degradation by predatory amoeba. Unicellular phagocytic are thought to be ancestors macrophages with highly conserved eukaryotic processes. Selection evolution within amoeba through their target processes have facilitated expansion host range mammals, causing various infectious diseases.

Language: Английский

Citations

12
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

7
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
Antimicrobial Efficacy of Five Wound Irrigation Solutions in the Periprosthetic Joint Infection Microenvironment In Vitro and Ex Vivo DOI Creative Commons
Annemarie Honegger, Tiziano A. Schweizer, Yvonne Achermann

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(1), P. 25 - 25

Published: Jan. 3, 2025

Background/Objectives: Periprosthetic joint infections (PJI) are difficult to treat due biofilm formation on implant surfaces and the surrounding tissue, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. Antiseptic irrigation during revision surgery might decrease bacterial load thereby improve treatment success. This in vitro study investigated compared effect five advanced wound solutions reduce burden PJI microenvironment. Methods: We treated biofilms grown titanium alloy discs clinical strains isolated from patients PJIs, as well abscess communities a plasma-supplemented collagen matrix. The were exposed for 1 min following solutions: Preventia®, Prontosan®, Granudacyn®, ActiMaris® forte ('Actimaris'), Octenilin®. measured reduction these Ringer-Lactate strong bactericidal but not approved Betaseptic solution. Additionally, ex vivo free-floating bacteria directly sonication fluids same way, regrowth lack was recorded outcome. Results: Irrigation demonstrated variable efficacy. mean CFU log10 follows: Octenilin, 3.07, Preventia, 1.17, Actimaris, 1.11, Prontosan, 1.03, Granudacyn, 0.61. For SACs, was: 8.27, 0.58, 0.56, 0.35, 0.24. Conclusions: All achieved complete eradication all tested fluids, except which ineffective 33% samples (2 out 6). Advanced have potential microenvironment surgery. However, their efficacy varies depending species, growth state, composition underscores importance considering factors when developing future PJI-specific solutions.

Language: Английский

Citations

0
Intravacuolar persistence in neutrophils facilitates Listeria monocytogenes spread to co-cultured cells DOI Creative Commons

Stefano Bagatella,

Camille Monney,

Norma Gross

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT The bacterium Listeria monocytogenes ( Lm ) causes listeriosis in humans and ruminants. Acute lesions are predominantly infiltrated by polymorphonuclear neutrophils (PMNs), considered to be the efficient bactericidal arm of innate immunity. However, recent evidence suggests that PMNs cannot achieve antilisterial sterilizing immunity may persist within PMNs. Despite this, interactions between remain poorly understood. In this study, we characterized listericidal activity interaction dynamics bovine with ex vivo . Phagocytosed failed escape into PMN cytosol was primarily targeted phagolysosomal mechanisms. enabled prolonged intravacuolar survival a resilient subpopulation, largely as viable but non-culturable (VBNC) bacteria. This population could spread from cell line, resuscitate, complete its canonical life cycle, thereby perpetuating infection. Therefore, identify mobile niche for provide harbor VBNC bacteria, potentially facilitating dissemination host. IMPORTANCE is significant foodborne pathogen responsible high hospitalization rates humans, especially vulnerable groups such elderly, pregnant women, immunocompromised individuals. animals like ruminants, infection leads severe disease manifestations, notably brainstem encephalitis. study uncovers novel mechanism which (PMNs) state, enabling bacteria hide PMNs, traditionally viewed killers, serve Trojan horses, allowing discovery has broad implications understanding 's persistence, role recurrent infections, development new therapeutic strategies targeting forms improve treatment outcomes control.

Language: Английский

Citations

0
Antibacterial compounds against non-growing and intracellular bacteria DOI Creative Commons
Niilo Kaldalu,

Normunds Bērziņš,

Stina Berglund Fick

et al.

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: April 11, 2025

Abstract Slow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments are linked to persistent recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against uropathogenic Escherichia coli (UPEC) we performed a drug-repurposing screen 6454 approved drugs drug candidates. Using dilution-regrowth assays, identified 39 that either kill UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, pleuromutilin, anti-cancer agents. Twenty-nine have not previously been recognized as were further tested Pseudomonas aeruginosa Staphylococcus aureus . Ten – solithromycin, rifabutin, mitomycin C, seven fluoroquinolones—have strong bactericidal activity P. , killing >4 log 10 bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, satraplatin unique in their ability selectively target bacteria, exhibiting poor efficacy growing Finally, 31 hit inhibit growth Shigella flexneri human enterocyte infection model, indicating permeate cytoplasm host cells. hold potential for treating infections, warranting comparative studies current standard-of-care antibiotics.

Language: Английский

Citations

0
Unraveling Persistent Bacteria: Formation, Niches, and Eradication Strategies DOI
Zhongqiong Yin,

D Huang,

E Kuhn

et al.

Microbiological Research, Journal Year: 2025, Volume and Issue: 297, P. 128189 - 128189

Published: April 23, 2025

Language: Английский

Citations

0