The Stringent Response and Antioxidant Defences in
            <i>Pseudomonas Aeruginosa</i>

Sampathkumar, Gowthami; Khakimova, Malika; Chan, Tevy; Nguyen, Dao M.

doi:10.1002/9781119004813.ch46

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…This study showed that (p)ppGpp signaling is necessary for optimal expression of catalase and superoxide dismutase enzymes as major ROS scavengers, but it was assumed to be indirectly regulated through a complex regulatory network (Sampathkumar et al, 2016 ; Figure 5 ). Because, (p)ppGpp signaling is also required for full expression of other regulatory pathways controlling antioxidant response such as the stress response regulator RpoS as well as both Las and Rhl QS systems (van Delden et al, 2001 ; Kohanski et al, 2008 ; Schafhauser et al, 2014 ; Sampathkumar et al, 2016 ; Figure 5 ). The proposed E. coli model for the activation of the TA system via Lon protease has not been shown for P. aeruginosa , yet.…”

Section: Survival By Stringent Response and Persister Formationmentioning

confidence: 99%

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Moradali

Ghods

Rehm

2017

Front. Cell. Infect. Microbiol.

1,101

1,016

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Pseudomonas aeruginosa is an opportunistic pathogen affecting immunocompromised patients. It is known as the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and as one of the leading causes of nosocomial infections. Due to a range of mechanisms for adaptation, survival and resistance to multiple classes of antibiotics, infections by P. aeruginosa strains can be life-threatening and it is emerging worldwide as public health threat. This review highlights the diversity of mechanisms by which P. aeruginosa promotes its survival and persistence in various environments and particularly at different stages of pathogenesis. We will review the importance and complexity of regulatory networks and genotypic-phenotypic variations known as adaptive radiation by which P. aeruginosa adjusts physiological processes for adaptation and survival in response to environmental cues and stresses. Accordingly, we will review the central regulatory role of quorum sensing and signaling systems by nucleotide-based second messengers resulting in different lifestyles of P. aeruginosa. Furthermore, various regulatory proteins will be discussed which form a plethora of controlling systems acting at transcriptional level for timely expression of genes enabling rapid responses to external stimuli and unfavorable conditions. Antibiotic resistance is a natural trait for P. aeruginosa and multiple mechanisms underlying different forms of antibiotic resistance will be discussed here. The importance of each mechanism in conferring resistance to various antipseudomonal antibiotics and their prevalence in clinical strains will be described. The underlying principles for acquiring resistance leading pan-drug resistant strains will be summarized. A future outlook emphasizes the need for collaborative international multidisciplinary efforts to translate current knowledge into strategies to prevent and treat P. aeruginosa infections while reducing the rate of antibiotic resistance and avoiding the spreading of resistant strains.

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Section: Survival By Stringent Response and Persister Formationmentioning

confidence: 99%

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Moradali

Ghods

Rehm

2017

Front. Cell. Infect. Microbiol.

1,101

1,016

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“…A 4-fold decrease in HEPB MIC (0.0625% (wt/vol) by agar dilution assay) was associated with mutation of a spoT homolog (Bcep1808_0918, mutant 22:E11). This gene putatively encodes a bifunctional (p)ppGpp synthase/hydrolase, a mediator of the stringent response, which coordinates a variety of cellular activities in response to change or adverse conditions ( 16 ). Also associated with the response to extracellular stimuli, the mutation of gene Bcep1808_3929 (mutant 35:G5) resulted in increased HEPB susceptibility.…”

Section: Resultsmentioning

confidence: 99%

“…This included parB gene homologs, shown to regulate stress response in Pseudomonas ( 21 ), and spoT , a mediator of the stringent response shown to influence expression of numerous genes with an effect on bacterial cell physiology that impacts antimicrobial susceptibility ( 41 ). Mutation of relA or spoT in P. aeruginosa has been shown to increase susceptibility to antimicrobials that cause oxidative stress ( 16 ). Transposable elements within Burkholderia have also been shown to have increased activity in response to oxidative stress ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…This included parB gene homologs, shown to regulate stress response in Pseudomonas (21), and spoT, a mediator of the stringent response shown to influence expression of numerous genes with an effect on bacterial cell physiology that impacts antimicrobial susceptibility (41). Mutation of relA or spoT in P. aeruginosa, have on October 29, 2020 by guest http://aem.asm.org/ Downloaded frombeen shown to increase susceptibility to antimicrobials that cause oxidative stress(16).…”

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confidence: 99%

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Mapping the Efficacy and Mode of Action of Ethylzingerone [4-(3-Ethoxy-4-Hydroxyphenyl) Butan-2-One] as an Active Agent against Burkholderia Bacteria

Rushton

Khodr

Ménard-Szczebara

et al. 2020

Appl Environ Microbiol

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Burkholderia cepacia complex (Bcc) bacteria are intrinsically antimicrobial resistant opportunistic pathogens and key risk species in the contamination of non-food industrial products. New agents and formulations to prevent growth of Burkholderia in home care (cleaning agents) and personal care (cosmetics and toiletries) products are required. We characterised how ethylzingerone [4-(3-ethoxy-4-hydroxyphenyl) butan-2-one)] (HEPB) acts as a preservative with activity against Burkholderia species encountered in industry. Burkholderia (n = 58) and non-Burkholderia (n = 7) bacteria were screened for susceptibility to HEPB, and its mode of action/resistance determined for a model B. vietnamiensis strain using transposon mutagenesis, transcriptomics and genome resequencing analysis. The susceptibility of Burkholderia spp. to HEPB (MIC = 0.45 ±0.11 % w/v; MBC = 0.90 ±0.3 % w/v) was characterised, with limited inter-/intra-species differences. HEPB (1% w/v) was rapidly bactericidal producing a 6-Log reduction in viability within 4 hours. Spontaneous resistance to HEPB did not develop, but transient phenotypes with altered growth characteristics and susceptibility to antibiotics were identified after prolonged exposure to sub-lethal HEPB concentrations. Transposon mutagenesis and RNA-sequencing analysis identified multiple genetic pathways associated with HEPB exposure, including stress response mechanisms, altered permeability, regulation of intracellular pH, damage/repair of intracellular components and alteration/repair of lipopolysaccharides. Key pathways included the stringent response, homeostasis of intracellular pH by the kdp operon, protection against electrophiles by KefC, and repair of oxidised proteins by methionine sulfoxide reductase enzymes. In summary, we show that HEPB has potent, targeted efficacy against Burkholderia bacteria without promoting wider stable antimicrobial resistance. The mode of action of HEPB against Burkholderia is multifactorial but killing by intracellular oxidation is a key mechanism of this promising agent. Importance. Burkholderia bacteria are opportunistic pathogens that can overcome preservatives used in the manufacture of non-sterile industrial products, and occasionally cause contamination. Consequently, new preservatives to prevent the growth of key risk Burkholderia cepacia complex bacteria in non-food industrial products are urgently required. Here we show that ethylzingerone is active against these problematic bacteria, killing them via a multifactorial mode of action which involves intracellular oxidation.

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The Pseudomonas aeruginosa DksA1 protein is involved in H2O2 tolerance and within-macrophages survival and can be replaced by DksA2

Fortuna

Collalto

Schiaffi³

et al. 2022

Sci Rep

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In Gram-negative pathogens, the stringent response regulator DksA controls the expression of hundreds of genes, including virulence-related genes. Interestingly, Pseudomonas aeruginosa has two functional DksA paralogs: DksA1 is constitutively expressed and has a zinc-finger motif, while DksA2 is expressed only under zinc starvation conditions and does not contain zinc. DksA1 stimulates the production of virulence factors in vitro and is required for full pathogenicity in vivo. DksA2 can replace these DksA1 functions. Here, the role of dksA paralogs in P. aeruginosa tolerance to H2O2-induced oxidative stress has been investigated. The P. aeruginosa dksA1 dksA2 mutant showed impaired H2O2 tolerance in planktonic and biofilm-growing cultures and increased susceptibility to macrophages-mediated killing compared to the wild type. Complementation with either dksA1 or dksA2 genes restored the wild type phenotypes. The DksA-dependent tolerance to oxidative stress involves, at least in part, the positive transcriptional control of both katA and katE catalase-encoding genes. These data support the hypothesis that DksA1 and DksA2 are eco-paralogs with indistinguishable function but optimal activity under different environmental conditions, and highlight their mutual contribution to P. aeruginosa virulence.

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The Stringent Response and Antioxidant Defences in Pseudomonas Aeruginosa

Cited by 4 publications

References 39 publications

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence

Mapping the Efficacy and Mode of Action of Ethylzingerone [4-(3-Ethoxy-4-Hydroxyphenyl) Butan-2-One] as an Active Agent against Burkholderia Bacteria

The Pseudomonas aeruginosa DksA1 protein is involved in H2O2 tolerance and within-macrophages survival and can be replaced by DksA2

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