Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus

Tkhilaishvili, Tamta; Lombardi, Lisa; Klatt, Ann-Brit; Trampuž, Andrej; Luca, Mariagrazia Di

doi:10.1016/j.ijantimicag.2018.09.006

Cited by 150 publications

(130 citation statements)

References 38 publications

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“…Furthermore, our method has been used to (i) determine that persister cells wake via ribosome activation (Kim et al, 2018b) and (ii) by activating chemotaxis (Yamasaki et al, 2019), (iii) show that the cells capable of resuscitation in a viable but not culturable population are equivalent to persister cells (Kim et al, 2018a), (iv) identify compounds that kill persister cells and (v) reveal that the alarmone ppGpp directly creates persister cells by stimulating ribosome dimerization . In addition, our method to generate a high population of persister cells has been utilized by at least six independent groups (Grassi et al, 2017;Cui et al, 2018;Narayanaswamy et al, 2018;Sulaiman et al, 2018;Tkhilaishvili et al, 2018;Pu et al, 2019).…”

Section: Bpoet Resuscitates E Coli Persister Cellsmentioning

confidence: 99%

Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD

Song

Wood

2019

Environmental Microbiology

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Summary Upon a wide range of stress conditions (e.g. nutrient, antibiotic, oxidative), a subpopulation of bacterial cells known as persisters survives by halting metabolism. These cells resuscitate rapidly to reconstitute infections once the stress is removed and nutrients are provided. However, how these dormant cells resuscitate is not understood well but involves reactivating ribosomes. By screening 10,000 compounds directly for stimulating Escherichia coli persister cell resuscitation, we identified that 2‐{[2‐(4‐bromophenyl)‐2‐oxoethyl]thio}‐3‐ethyl‐5,6,7,8‐tetrahydro[1]benzothieno[2,3‐d]pyrimidin‐4(3H)‐one (BPOET) stimulates resuscitation. Critically, by screening 4267 E. coli proteins, we determined that BPOET activates hibernating ribosomes via 23S rRNA pseudouridine synthase RluD, which increases ribosome activity. Corroborating the increased waking with RluD, production of RluD increased the number of active ribosomes in persister cells. Also, inactivating the small RNA RybB which represses rluD led to faster persister resuscitation. Hence, persister cells resuscitate via activation of RluD.

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Section: Bpoet Resuscitates E Coli Persister Cellsmentioning

confidence: 99%

Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD

Song

Wood

2019

Environmental Microbiology

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“…The persister cells generated in this way have been (i) confirmed eight ways (19), (ii) used to determine that persister cells wake via ribosome activation (19) and chemotaxis (20), (iii) used to show that the cells capable of resuscitation in a viable but not culturable 95 population are equivalent to persister cells (15), (iv) used to identify compounds that kill persister cells (27), and (v) used to show that the alarmone ppGpp directly creates persister cells by stimulating ribosome dimerization (16). In addition, our method to generate a high population of persister cells has been utilized by at least six independent groups (28)(29)(30)(31)(32)(33).…”

Section: Resultsmentioning

confidence: 99%

Persister Cells Resuscitate via Ribosome Modification by 23S rRNA Pseudouridine Synthase RluD

Song

Wood

2019

Preprint

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Upon a wide range of stress conditions (e.g., nutrient, antibiotic, oxidative), a subpopulation of bacterial cells known as persisters survive by halting metabolism. These cells resuscitate rapidly to reconstitute infections once the stress is removed and nutrients are provided. However, how these dormant cells resuscitate is not understood well but involves reactivating ribosomes. By screening 10,000 5 compounds directly for stimulating Escherichia coli persister cell resuscitation, we identified that 2-{[2-(4-bromophenyl)-2-oxoethyl]thio}-3-ethyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (BPOET) stimulates resuscitation. Critically, by screening 4,267 E. coli proteins, we determined that BPOET activates hibernating ribosomes via 23S rRNA pseudouridine synthase RluD, which increases ribosome activity. Corroborating the increased waking with RluD, production of RluD increased the 10 number of active ribosomes in persister cells. Also, inactivating the small RNA RybB which represses rluD led to faster persister resuscitation. Hence, persister cells resuscitate via activation of RluD.

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“…; Tkhilaishvili et al . ; Pu et al . ) and have been shown to be effective not only for E. coli but also for P. aeruginosa and S. aureus .…”

Section: Introductionmentioning

confidence: 99%

“…The persister cells generated by rifampicin pretreatment have been validated via eight different assays (multi-drug tolerance, immediate change from persister to nonpersister in the presence of nutrients, two lines of evidence for dormancy, no change in the minimum inhibitory concentration compared to exponential cells, no resistance phenotype, similar morphology to ampicillin-induced persisters and similar resuscitation as ampicillin-induced persisters) (Kim et al 2018a). Our chemical methods have also been validated by six independent groups in recent months (Grassi et al 2017;Cui et al 2018;Narayanaswamy et al 2018;Sulaiman et al 2018;Tkhilaishvili et al 2018;Pu et al 2019) and have been shown to be effective not only for E. coli but also for P. aeruginosa and S. aureus.…”

Section: Introductionmentioning

confidence: 99%

Interkingdom signal indole inhibits Pseudomonas aeruginosa persister cell waking

et al. 2019

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Aims Persister cells are stressed cells that have transient tolerance to antibiotics; these cells undergo no genetic change, but instead, their tolerance is due to reduced metabolism. Unfortunately, little is known about how persisters resuscitate, so we explored the waking of cells in the presence of the interkingdom signal indole. Methods and Results To generate a large population of persister cells, we induced the persister phenotype in the opportunistic pathogen Pseudomonas aeruginosa by pretreating cells with carbonyl cyanide m‐chlorophenylhydrazone to reduce translation by depleting ATP levels, and found, via single cell observations, that proline is sufficient to wake the persister cells. P. aeruginosa is often present in the gastrointestinal tract, and indole from commensal bacteria such as Escherichia coli has been shown to inhibit P. aeruginosa quorum sensing and pathogenicity without influencing growth. Furthermore, indole is not toxic to P. aeruginosa persister cells. However, we find here that physiological concentrations of indole inhibit P. aeruginosa persister cell resuscitation with an efficiency of higher than 95%. Critically, when contacted with E. coli stationary‐phase cultures, the indole produced by E. coli completely inhibits persister cell resuscitation of P. aeruginosa. Conclusions Therefore, E. coli has devised a method to outcompete its competitors by preventing their resuscitation with indole. Significance and Impact of the Study This work provides insight into why indole is produced by commensal bacteria.

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Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus

Cited by 150 publications

References 38 publications

Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD

Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD

Persister Cells Resuscitate via Ribosome Modification by 23S rRNA Pseudouridine Synthase RluD

Interkingdom signal indole inhibits Pseudomonas aeruginosa persister cell waking

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