Delayed host mortality and immune response upon infection with P. aeruginosa persister cells DOI

Cody James Hastings,

Maya V. Keledjian,

Laura Palanker Musselman

et al.

Infection and Immunity, Journal Year: 2023, Volume and Issue: 91(10)

Published: Sept. 21, 2023

Chronic infections are a heavy burden on healthcare systems worldwide. Persister cells thought to be largely responsible for chronic infection due their tolerance antimicrobials and recalcitrance innate immunity factors. Pseudomonas aeruginosa is common clinically relevant pathogen that contains stereotypical persister cells. Despite importance in infection, there have been limited efforts study cell vivo. Drosophila melanogaster has well-described immune response similar of vertebrates good candidate the development an vivo model Similar what observed other bacterial strains, this work we found with P. resulted delayed mortality phenotype Caenorhabditis elegans, Arabidopsis thaliana, D. compared regular An in-depth characterization infected loads differed between cells' during early stages. Furthermore, hemocyte activation antimicrobial peptide expression were delayed/reduced over same time course, indicating initial suppression of, or inability elicit, fly response. Overall, our findings support use as which vivo, where subpopulation exhibits virulence attenuated

Language: Английский

Targeting Bacterial Persisters via Reactive Oxygen Species‐Generating Hydrogel Microspheres DOI
Yanyang Chen, Tao Ding, Yawei Du

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(46)

Published: June 19, 2024

Abstract The presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, platform developed, called reactive oxygen species (ROS) bomb, based on microenvironment‐adaptive hydrogel microspheres, oxidize the cell membranes in periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and glucose oxidase (GOx)/calcium phosphate (CaP) acid‐responsive shell sequentially induced surface mesoporous polydopamine (PDA) nanoparticles by PDA‐mediated ion precipitation interfacial adhesion, followed coloaded with into microfluidic hyaluronic acid microspheres. Hydroxyl radicals explosively generated through GOx‐mediated oxidase, H 2 O production, its Fenton‐like reactions FeOOH, which also benefit from weakly acidic microenvironment around persisters, result destruction membrane, subsequent overflow cellular contents such as dsDNA, proteins, K + . bactericidal rates methicillin‐resistant Staphylococcus aureus epidermidis up 99.14% 98.96%, loads lesion location significantly decreased after ROS bombs treated, effectively alleviated inflammation bone resorption damage. This work provides new strategy toward clearance shows great application potential other infection‐related diseases.

Language: Английский

Citations

9
Resuscitation dynamics reveal persister partitioning after antibiotic treatment DOI Creative Commons
Xin Fang,

Kyle R. Allison

Molecular Systems Biology, Journal Year: 2023, Volume and Issue: 19(4)

Published: March 3, 2023

Language: Английский

Citations

13
An isogenic E. coli population gives rise to multiple persister phenotypes DOI Creative Commons
K. M. Taufiqur Rahman,

Ruqayyah Amaratunga,

Xuan Yi Butzin

et al.

International Journal of Antimicrobial Agents, Journal Year: 2024, Volume and Issue: unknown, P. 107386 - 107386

Published: Nov. 1, 2024

Language: Английский

Citations

3
Ribosome inactivation by Escherichia coli GTPase RsgA inhibits T4 phage DOI Creative Commons
Laura Fernández‐García, María Tomás, Thomas K. Wood

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 21, 2023

Introduction Bacteria must combat phages, and myriad bacterial anti-phage systems have been discovered that reduce host metabolism, for example, by depleting energetic compounds like ATP NAD + . Hence, these indirectly inhibit protein production. Surprisingly, direct reduction of ribosome activity has not demonstrated to thwart phage. Methods Here, producing each the 4,287 Escherichia coli proteins selecting leads enhanced growth, we investigated role in phage inhibition. Results discussion We identified E. GTPase RsgA inhibits lytic T4 inactivating ribosomes.

Language: Английский

Citations

6
Antibiotic heteroresistance and persistence: an additional aid in hospital acquired infections by Enterococcus spp.? DOI
Catarina Geraldes, Luís Tavares, Solange Gil

et al.

Future Microbiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 12

Published: Sept. 4, 2024

, particularly

Language: Английский

Citations

2
Escherichia coli self-organizes developmental rosettes DOI Creative Commons
Devina Puri,

Kyle R. Allison

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(23)

Published: May 30, 2024

Rosettes are self-organizing, circular multicellular communities that initiate developmental processes, like organogenesis and embryogenesis, in complex organisms. Their formation results from the active repositioning of adhered sister cells is thought to distinguish organisms unicellular ones. Though common eukaryotes, this behavior has not been reported bacteria. In study, we found

Language: Английский

Citations

1
Hyperbaric oxygen therapy counteracts Pseudomonas aeruginosa biofilm micro-compartment phenomenon in murine thermal wounds DOI Creative Commons
Anne Sofie Laulund, Franziska Angelika Schwartz, Niels Høiby

et al.

Biofilm, Journal Year: 2023, Volume and Issue: 6, P. 100159 - 100159

Published: Sept. 26, 2023

Biofilm antibiotic tolerance is partly explained by the behavior of a biofilm as an independent pharmacokinetic micro-compartment. Hyperbaric oxygen therapy has been shown to potentiate effects in biofilms. The present study investigates effect hyperbaric (HBOT) on micro-pharmacokinetic/pharmacodynamic tobramycin animal model.Full-thickness necroses were created mid-scapular mice means thermal lesion. After four days, three 16 h seaweed alginate beads containing Pseudomonas aeruginosa PAO1 inserted under necrosis, and adjacent non-affected skin. randomized groups I) HBOT for 1.5 at 2.8 atm 0.8 mg tobramycin/mouse subcutaneously; II) Tobramycin monotherapy, same dose; III) Saline control group. Half number from group 1 2 sacrificed, recovered toto after 3 other half placebo sacrificed collected 4.5 h.Lower CFUs seen burned receiving compared atmospheric environment (p = 0.043 p 0.0089). At h, no CFU difference was observed non-burned skin (HBOT vs atmospheric). had lower corresponding 0.02). higher than when applied 0.04), faded out h.At both time points, content 0.031 0.0078). Only HBOT-treated 0.006).HBOT, anti-biofilm adjuvant treatment chronic wounds, counteracts micro-compartmentalization through increased available augmented bacterial killing.

Language: Английский

Citations

3
Differential impacts of DNA repair machinery on fluoroquinolone persisters with different chromosome abundances DOI Creative Commons

Juechun Tang,

Allison M. Herzfeld,

Gabrielle Leon

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 2, 2024

DNA repair machinery has been found to be indispensable for fluoroquinolone (FQ) persistence of Escherichia coli. Previously, we that cells harboring two copies the chromosome (2Chr) in stationary-phase cultures were more likely yield FQ persisters than those with one copy (1Chr). Furthermore, RecA and RecB required observe difference, loss either significantly impacted 2Chr 1Chr persisters. To better understand survival mechanisms different abundances, examined their dependencies on proteins. Here, show lexA3 ∆recN negatively impact abundances FQs, without significant impacts In comparison, ∆xseA, ∆xseB, ∆uvrD preferentially depress levels near limit detection. Collectively, these data used by vary based number, suggest efforts eradicate will have take heterogeneity single-cell abundance into consideration. Persisters are rare phenotypic variants isogenic populations survive antibiotic treatments kill other present. Evidence accumulated supports a role chronic recurrent infections. explore how an under-appreciated variable, number (#Chr), influences systems use treatments. We #Chr biases persisters, which suggests should considered when devising strategies troublesome bacterial variants.

Language: Английский

Citations

0
Pheromone cCF10 inhibits the antibiotic persistence of Enterococcus faecalis by modulating energy metabolism DOI Creative Commons
Zhu Li,

Xiaobo Yang,

Xinyue Fu

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 8, 2024

Introduction Bacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing key role. Multiple studies were recently undertaken examine factors influencing formation of persisters underlying process, primary focus on Gram-negative bacteria Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis ( E. ) is capable causing variety infectious diseases, but there have been few persisters. Previous shown that sex pheromone cCF10 secreted by induces conjugative plasmid transfer. However, whether regulates has not investigated. Methods As result, we investigated effect potential molecular mechanism in regulating OG1RF using persistent model. Results discussion The metabolically active reached state temporarily tolerated lethal antibiotic concentrations after 8 h levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting rate 0.109 %. During growth OG1RF, biofilm was critical factor contributing persistence, whereas 10 ng/mL blocked persister cell formation. Notably, mediated via metabolic activity rather than suppressing addition stimulated Opp system entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining reducing generation. These findings offer valuable insights into formation, as well control

Language: Английский

Citations

0
Metabolite dependence of antibiotic susceptibility in a gut microbe DOI Creative Commons

Kyle R. Allison

mSphere, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Antibiotics save lives but can have unwanted effects on our gut microbes, thereby contributing to disease. A mechanistic understanding of how such microbes respond antibiotics is hence critical. Recently in

Language: Английский

Citations

0