Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa

Background: Planktonic stationary and exponential cultures of Pseudomonas aeruginosa are highly resistant to killing by bactericidal antimicrobials because of the presence of persisters, cells that are multidrug tolerant and play a key role in the recalcitrance of biofilm infections. Aim: The aim of...

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Main Authors: Patrik Mlynarcik, Milan Kolar
Format: Article
Language:English
Published: Palacký University Olomouc, Faculty of Medicine and Dentistry 2017-03-01
Series:Biomedical Papers
Subjects:
Online Access:https://biomed.papers.upol.cz/artkey/bio-201701-0008_Starvation-_and_antibiotics-induced_formation_of_persister_cells_in_Pseudomonas_aeruginosa.php
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author Patrik Mlynarcik
Milan Kolar
author_facet Patrik Mlynarcik
Milan Kolar
author_sort Patrik Mlynarcik
collection DOAJ
description Background: Planktonic stationary and exponential cultures of Pseudomonas aeruginosa are highly resistant to killing by bactericidal antimicrobials because of the presence of persisters, cells that are multidrug tolerant and play a key role in the recalcitrance of biofilm infections. Aim: The aim of this study was to investigate the formation of persister cells in P. aeruginosa stationary vs. exponential cultures using different class antimicrobials. Methods: The susceptibilities of P. aeruginosa PAO1 wild-type and mutant strains to antimicrobials were determined by standard microtiter broth dilution method. In order to determine persister formation, dose- and time-dependent killing experiments were performed with antibiotics. Results: Ceftazidime (Cephalosporin) showed little efficacy against either culture. Stationary-phase cells were more tolerant to imipenem (Carbapenem) than exponential cells, leaving a small fraction of persisters at high imipenem concentration in both populations. Polymyxin B (Polymyxin) appeared to be ineffective at low concentrations against both cell populations. Very high polymyxin B concentration completely eradicated exponential cells and regrowth was seen in a stationary population. Stationary cells were more tolerant to tobramycin (Aminoglycoside) than exponential cells but a higher concentration of tobramycin completely eliminated survivors. Ciprofloxacin (Fluoroquinolone) at a low concentration resulted in killing of both cultures of P. aeruginosa, producing persisters that were invulnerable to killing. Conclusions: Stationary cells appear to be somewhat more tolerant than exponential cells in all of these assays. We also showed that nutrient deprivation (serine starvation) regulated by stringent and general stress response, contribute to the increased tolerance of P. aeruginosa exponential and stationary planktonic cells via production of persisters.
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spelling doaj.art-b4d0d6c8e596436bb6efecf8644c9c2a2022-12-22T03:40:08ZengPalacký University Olomouc, Faculty of Medicine and DentistryBiomedical Papers1213-81181804-75212017-03-011611586710.5507/bp.2016.057bio-201701-0008Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosaPatrik Mlynarcik0Milan Kolar1Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech RepublicDepartment of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech RepublicBackground: Planktonic stationary and exponential cultures of Pseudomonas aeruginosa are highly resistant to killing by bactericidal antimicrobials because of the presence of persisters, cells that are multidrug tolerant and play a key role in the recalcitrance of biofilm infections. Aim: The aim of this study was to investigate the formation of persister cells in P. aeruginosa stationary vs. exponential cultures using different class antimicrobials. Methods: The susceptibilities of P. aeruginosa PAO1 wild-type and mutant strains to antimicrobials were determined by standard microtiter broth dilution method. In order to determine persister formation, dose- and time-dependent killing experiments were performed with antibiotics. Results: Ceftazidime (Cephalosporin) showed little efficacy against either culture. Stationary-phase cells were more tolerant to imipenem (Carbapenem) than exponential cells, leaving a small fraction of persisters at high imipenem concentration in both populations. Polymyxin B (Polymyxin) appeared to be ineffective at low concentrations against both cell populations. Very high polymyxin B concentration completely eradicated exponential cells and regrowth was seen in a stationary population. Stationary cells were more tolerant to tobramycin (Aminoglycoside) than exponential cells but a higher concentration of tobramycin completely eliminated survivors. Ciprofloxacin (Fluoroquinolone) at a low concentration resulted in killing of both cultures of P. aeruginosa, producing persisters that were invulnerable to killing. Conclusions: Stationary cells appear to be somewhat more tolerant than exponential cells in all of these assays. We also showed that nutrient deprivation (serine starvation) regulated by stringent and general stress response, contribute to the increased tolerance of P. aeruginosa exponential and stationary planktonic cells via production of persisters.https://biomed.papers.upol.cz/artkey/bio-201701-0008_Starvation-_and_antibiotics-induced_formation_of_persister_cells_in_Pseudomonas_aeruginosa.phpantimicrobialspersisterstolerancep. aeruginosaplanktonicserine hydroxamatemutant
spellingShingle Patrik Mlynarcik
Milan Kolar
Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
Biomedical Papers
antimicrobials
persisters
tolerance
p. aeruginosa
planktonic
serine hydroxamate
mutant
title Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
title_full Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
title_fullStr Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
title_full_unstemmed Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
title_short Starvation- and antibiotics-induced formation of persister cells in Pseudomonas aeruginosa
title_sort starvation and antibiotics induced formation of persister cells in pseudomonas aeruginosa
topic antimicrobials
persisters
tolerance
p. aeruginosa
planktonic
serine hydroxamate
mutant
url https://biomed.papers.upol.cz/artkey/bio-201701-0008_Starvation-_and_antibiotics-induced_formation_of_persister_cells_in_Pseudomonas_aeruginosa.php
work_keys_str_mv AT patrikmlynarcik starvationandantibioticsinducedformationofpersistercellsinpseudomonasaeruginosa
AT milankolar starvationandantibioticsinducedformationofpersistercellsinpseudomonasaeruginosa