Functional Analysis of spoT, relA and dksA Genes on Quinolone Tolerance in Pseudomonas aeruginosa under Nongrowing Condition

Viducic, Darija; Ono, Tsuneko; Murakami, Keiji; Susilowati, Heni; Kayama, Shizuo; Hirota, Kaoru; Miyake, Yoichiro

doi:10.1111/j.1348-0421.2006.tb03793.x

Cited by 83 publications

(78 citation statements)

References 30 publications

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“…A current theory proposed for persister formation in E. coli postulates that stochastic fluctuation in the production of toxic proteins known to block cell metabolism mediates entrance of cells into a dormant state enabling the persister cell to escape corruption of cellular functions by antibiotics (32). However, in both E. coli and P. aeruginosa a number of the genes that were identified to affect the persister phenotype encode global regulators, such as DnaK, DnaJ, DksA, histone-like protein, integration host factor (17), and PhoU (34) in E. coli or SpoT, RelA, DksA (62), and RpoS (42) in P. aeruginosa, suggesting that environmental signaling plays an important role in modulating persistence.…”

Section: Discussionmentioning

confidence: 99%

“…One hypothesis about the underlying mechanism for persister formation is that persister cells are phenotypic variants which are not regulated per se but result from stochastic fluctuations of toxic proteins (32). However, several genes, including genes encoding the global stationary phase-related regulators SpoT, RelA, DskA, and RpoS (42,62), that appear to be involved in persistence in P. aeruginosa have been discovered (9,42,62). We undertook to investigate the formation of persister cells in P. aeruginosa cultures in a comprehensive analysis under various conditions related to cidal and static antibiotic challenge, quorum-sensing-mediated signaling, and environmental stress conditions.…”

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confidence: 99%

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Pseudomonas aeruginosaIncreases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules

Möker¹,

Dean²,

Tao³

2010

J Bacteriol

217

177

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Bacterial persister cells constitute a small portion of a culture which is tolerant to killing by lethal doses of bactericidal antibiotics. These phenotypic variants are formed in numerous bacterial species, including those with clinical relevance like the opportunistic pathogen Pseudomonas aeruginosa. Although persisters are believed to contribute to difficulties in the treatment of many infectious diseases, the underlying mechanisms affecting persister formation are not well understood. Here we show that even though P. aeruginosa cultures have a significantly smaller fraction of multidrug-tolerant persister cells than cultures of Escherichia coli or Staphylococcus aureus, they can increase persister numbers in response to quorum-sensing-related signaling molecules. The phenazine pyocyanin (and the closely related molecule paraquat) and the acyl-homoserine lactone 3-OC12-HSL significantly increased the persister numbers in logarithmic P. aeruginosa PAO1 or PA14 cultures but not in E. coli or S. aureus cultures.Over the last 50 years, Pseudomonas aeruginosa has emerged as a major cause of nosocomial infections in immunocompromised patients, including those relying on mechanical ventilation and suffering from neutropenia or severe burns, and is perhaps most well known as the agent primarily responsible for the decline in lung function leading to death in cystic fibrosis (CF) patients (8,14,16,23,38). P. aeruginosa possesses a multiplicity of virulence factors that are elicited upon access to susceptible individuals, including various toxins, secretion systems, siderophores, surface appendages, endotoxin (lipopolysaccharide [LPS]), alginate, and phenazines. These can generate acute toxicity/injury, leading P. aeruginosa to be labeled as the "hyena" of the bacterial world (15). Treatment of infections by P. aeruginosa is hindered by its high level of intrinsic resistance to antibiotics due primarily to a combination of the impermeable outer membrane and a number of broad-spectrum efflux pumps (50, 51). P. aeruginosa is also thought to enter into a biofilm mode of growth in CF lung infections (36,48,63), contributing both to pathogenicity/colonization and resistance to therapeutic intervention.In P. aeruginosa, global regulation, mediated by at least 3 quorum-sensing (QS) systems, controls population behaviors and synthesis of the majority of these pathogenicity factors (59, 66). This bacterium possesses two N-acyl-homoserine lactone (HSL)-mediated quorum-sensing systems, las and rhl (26,43,46,47), and a Pseudomonas quinolone signal (PQS) system mediated by 2-heptyl-3-hydroxy-4-quinolone (49). In the HSL-mediated systems, the HSL synthases LasI and RhlI are responsible for the synthesis of the autoinducers N-(3-oxododecanoyl)-L-HSL (3-OC12-HSL) and N-butyryl-L-HSL (C4-HSL), respectively. Expressions of the lasI and rhl genes are regulated by the transcriptional activators LasR and RhlR in response to their cognate HSL signal molecules. Among the numerous cellular and secreted virulence factors in P. aeruginosa whose...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pseudomonas aeruginosaIncreases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules

Möker¹,

Dean²,

Tao³

2010

J Bacteriol

217

177

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“…In P. aeruginosa, it was shown that spoT and dksA mutants had higher levels of ppGpp and were more tolerant toward fluoroquinolones (118). Furthermore, in P. aeruginosa, the stringent response is required for optimal catalase activity and mediates H 2 O 2 tolerance during both planktonic and biofilm growth.…”

Section: Persisters Play a Central Role In Biofilm Recalcitrance Towamentioning

confidence: 99%

Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics

Lebeaux

Ghigo

Beloin

2014

Microbiol Mol Biol Rev

1,050

862

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International audienceSurface-associated microbial communities, called biofilms, are present in all environments. Although biofilms play an important positive role in a variety of ecosystems, they also have many negative effects, including biofilm-related infections in medical settings. The ability of pathogenic biofilms to survive in the presence of high concentrations of antibiotics is called "recalcitrance" and is a characteristic property of the biofilm lifestyle, leading to treatment failure and infection recurrence. This review presents our current understanding of the molecular mechanisms of biofilm recalcitrance toward antibiotics and describes how recent progress has improved our capacity to design original and efficient strategies to prevent or eradicate biofilm-related infections

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“…For example, both in E. coli and in P. aeruginosa, these include dksA, relA and spoT, genes associated with the stringent response (Hansen et al, 2008;Korch et al, 2003;Viducic et al, 2006). However, because of their simultaneous involvement in additional processes, their suitability as candidate drug targets remains to be determined.…”

Section: Global Regulatorsmentioning

confidence: 99%

Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies

Fauvart

Groote

Michiels

2011

Journal of Medical Microbiology

375

319

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Functional Analysis of spoT, relA and dksA Genes on Quinolone Tolerance in Pseudomonas aeruginosa under Nongrowing Condition

Cited by 83 publications

References 30 publications

Pseudomonas aeruginosaIncreases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules

Pseudomonas aeruginosaIncreases Formation of Multidrug-Tolerant Persister Cells in Response to Quorum-Sensing Signaling Molecules

Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics

Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies

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