The Role of Integration Host Factor in Escherichia coli Persister Formation DOI

Samantha Nicolau,

Kim Lewis

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 4, 2022

Persisters represent a small subpopulation of cells that are tolerant killing by antibiotics and implicated in the recalcitrance chronic infections to antibiotic therapy. One general theme has emerged regarding persisters formed different bacterial species, namely, state relative dormancy characterized diminished activity targets. Within this framework, number studies have linked persister formation stochastic decreases energy-generating components, leading low ATP target activity. In study, we screen knockouts main global regulators Escherichia coli for their effect on persisters. A knockout integration host factor (IHF) had elevated level This was accompanied an overexpression isocitrate dehydrogenase (Icd) downregulation lyase (AceA), two genes located at bifurcation between tricarboxylic acid (TCA) cycle glyoxylate bypass. Using translational ihfA-mVenus fusion, sort out rare bright cells, is enriched Our results suggest noise expression ihf produces with Icd/high AceA, diverting substrates into bypass, which ATP, antibiotic-tolerant We further examine simple model, lac operon, show lacI repressor increases operon formation. quenching serves as approach determine nature variety species conditions. IMPORTANCE phenotypic variants survive exposure through temporary dormancy. Mutants increased levels been identified clinical isolates, evidence suggests these contribute treatment failure. Understanding underlying mechanism tolerance important developing therapeutic approaches treat infections. regulator, IHF, plays role find IHF contributes formation, likely regulating switch TCA efficiently energy extend study model when grown lactose sole carbon source, its influences determines quenched providing test involvement gene

Language: Английский

Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes DOI
Felipe C. Cabello, Monica E. Embers, Stuart A. Newman

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(3)

Published: April 25, 2022

The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi , is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten 20% antimicrobial-treated disease patients display posttreatment syndrome (PTLDS), a clinical complication whose etiology pathogenesis remain uncertain.

Language: Английский

Citations

22
Serine-threonine phosphoregulation by PknB and Stp contributes to quiescence and antibiotic tolerance in Staphylococcus aureus DOI
Markus Huemer, Srikanth Mairpady Shambat, Sanne Hertegonne

et al.

Science Signaling, Journal Year: 2023, Volume and Issue: 16(766)

Published: Jan. 3, 2023

Staphylococcus aureus can cause infections that are often chronic and difficult to treat, even when the bacteria not antibiotic resistant because most antibiotics act only on metabolically active cells. Subpopulations of persister cells quiescent, a state associated with delayed growth, reduced protein synthesis, increased tolerance antibiotics. Serine-threonine kinases phosphatases similar those found in eukaryotes fine-tune essential bacterial cellular processes, such as metabolism stress signaling. We acid stress-mimicking conditions S. experiences host tissues globally altered serine threonine phosphoproteome, phosphorylation activation loop serine-threonine kinase B (PknB). The deletion stp, which encodes annotated functional phosphatase aureus, growth delay phenotypic heterogeneity under different challenges, including acidic conditions, intracellular milieu human cells, abscesses mice. This was translation ATP concentrations tolerance. Using phosphopeptide enrichment mass spectrometry-based proteomics, we identified targets may regulate metabolism. Together, our findings highlight importance phosphoregulation mediating quiescence suggest targeting PknB or Stp might offer future therapeutic strategy prevent formation during infections.

Language: Английский

Citations

13
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
Dissecting cell heterogeneities in bacterial biofilms and their implications for antibiotic tolerance DOI

Mayra C Obando,

Diego O. Serra

Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 78, P. 102450 - 102450

Published: Feb. 28, 2024

Language: Английский

Citations

5
The Role of Integration Host Factor in Escherichia coli Persister Formation DOI

Samantha Nicolau,

Kim Lewis

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 4, 2022

Persisters represent a small subpopulation of cells that are tolerant killing by antibiotics and implicated in the recalcitrance chronic infections to antibiotic therapy. One general theme has emerged regarding persisters formed different bacterial species, namely, state relative dormancy characterized diminished activity targets. Within this framework, number studies have linked persister formation stochastic decreases energy-generating components, leading low ATP target activity. In study, we screen knockouts main global regulators Escherichia coli for their effect on persisters. A knockout integration host factor (IHF) had elevated level This was accompanied an overexpression isocitrate dehydrogenase (Icd) downregulation lyase (AceA), two genes located at bifurcation between tricarboxylic acid (TCA) cycle glyoxylate bypass. Using translational ihfA-mVenus fusion, sort out rare bright cells, is enriched Our results suggest noise expression ihf produces with Icd/high AceA, diverting substrates into bypass, which ATP, antibiotic-tolerant We further examine simple model, lac operon, show lacI repressor increases operon formation. quenching serves as approach determine nature variety species conditions. IMPORTANCE phenotypic variants survive exposure through temporary dormancy. Mutants increased levels been identified clinical isolates, evidence suggests these contribute treatment failure. Understanding underlying mechanism tolerance important developing therapeutic approaches treat infections. regulator, IHF, plays role find IHF contributes formation, likely regulating switch TCA efficiently energy extend study model when grown lactose sole carbon source, its influences determines quenched providing test involvement gene

Language: Английский

Citations

19