Blocking RpoN reduces virulence of Pseudomonas aeruginosa isolated from cystic fibrosis patients and increases antibiotic sensitivity in a laboratory strain

Lloyd, Megan G; Vossler, James L.; Nomura, Christopher T.; Moffat, Jennifer F.

doi:10.1038/s41598-019-43060-6

Cited by 18 publications

(9 citation statements)

References 54 publications

(64 reference statements)

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“…Genetic features of P. aeruginosa have been widely investigated for the strains isolated from the respiratory tract [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ], urinary tract [ 20 , 21 , 22 ], wounds [ 10 , 18 , 23 , 24 , 25 , 26 ] or many different origins simultaneously [ 27 ]. Meanwhile, relatively little is known about the association between genetic features and P. aeruginosa strains’ ability to cause BSIs.…”

Section: Discussionmentioning

confidence: 99%

Decoding Genetic Features and Antimicrobial Susceptibility of Pseudomonas aeruginosa Strains Isolated from Bloodstream Infections

Bogiel¹,

Depka²,

Rzepka³

et al. 2022

IJMS

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Pseudomonas aeruginosa is a Gram-negative rod and an etiological factor of opportunistic infections. The infections of this etiology appear mostly among hospitalized patients and are relatively hard to treat due to widespread antimicrobial resistance. Many virulence factors are involved in the pathogenesis of P. aeruginosa infection, the coexistence of which have a significant impact on the course of an infection with a particular localization. The aim of this study was to assess the antimicrobial susceptibility profiles and the frequency of genes encoding selected virulence factors in clinical P. aeruginosa strains isolated from bloodstream infections (BSIs). The following genes encoding virulence factors of enzymatic activity were assessed: lasB, plC H, plC N, nan1, nan2, aprA and phzM. The frequency of the genes encoding the type III secretion system effector proteins (exoU and exoS) and the genes encoding pilin structural subunits (pilA and pilB) were also investigated. The occurrence of virulence-factor genes was assessed using polymerase chain reactions, each in a separate reaction. Seventy-one P. aeruginosa strains, isolated from blood samples of patients with confirmed bacteremia hospitalized at the University Hospital No. 1 of Dr. Antoni Jurasz in Bydgoszcz, Poland, were included in the study. All the investigated strains were susceptible to colistin, while the majority of the strains presented resistance to ticarcillin/clavulanate (71.8%), piperacillin (60.6 %), imipenem (57.7%) and piperacillin/tazobactam (52.1%). The presence of the lasB and plC H genes was noted in all the tested strains, while the plC N, nan2, aprA, phzM and nan1 genes were identified in 68 (95.8%), 66 (93.0%), 63 (88.7%), 55 (77.5%) and 34 (47.9%) isolates, respectively. In 44 (62.0%) and 41 (57.7%) strains, the presence of the exoU and exoS genes was confirmed, while the pilA and pilB genes were noted only in 14 (19.7%) and 3 (4.2%) isolates, respectively. This may be due to the diverse roles of these proteins in the development and maintenance of BSIs. Statistically significant correlations were observed between particular gene pairs’ coexistence (e.g., alkaline protease and neuraminidase 2). Altogether, twenty-seven distinctive genotypes were observed among the studied strains, indicating the vast variety of genetic compositions of P. aeruginosa strains causing BSIs.

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Section: Discussionmentioning

confidence: 99%

Decoding Genetic Features and Antimicrobial Susceptibility of Pseudomonas aeruginosa Strains Isolated from Bloodstream Infections

Bogiel¹,

Depka²,

Rzepka³

et al. 2022

IJMS

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“…The expression of ndvB in biofilms is dependent on the stationary-phase sigma factor RpoS [759] which is the master regulator of general stress responses [760]. Blocking the alternative sigma factor RpoN (σ 54 ), which regulates many virulence factors, increased the susceptibility of Pseudomonas aeruginosa to β-lactam antibiotics [761].…”

Section: Activation Of Protective Stress Responsesmentioning

confidence: 99%

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Sionov

Steinberg

2022

Microorganisms

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Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that are composed of mono- or multi-species cultures of bacteria/fungi embedded in an extracellular matrix produced by the microorganisms. Biofilm formation is, among others, regulated by quorum sensing (QS) which is an interbacterial communication system usually composed of two-component systems (TCSs) of secreted autoinducer compounds that activate signal transduction pathways through interaction with their respective receptors. Embedded in the biofilms, the bacteria are protected from environmental stress stimuli, and they often show reduced responses to antibiotics, making it difficult to eradicate the bacterial infection. Besides reduced penetration of antibiotics through the intricate structure of the biofilms, the sessile biofilm-embedded bacteria show reduced metabolic activity making them intrinsically less sensitive to antibiotics. Moreover, they frequently express elevated levels of efflux pumps that extrude antibiotics, thereby reducing their intracellular levels. Some efflux pumps are involved in the secretion of QS compounds and biofilm-related materials, besides being important for removing toxic substances from the bacteria. Some efflux pump inhibitors (EPIs) have been shown to both prevent biofilm formation and sensitize the bacteria to antibiotics, suggesting a relationship between these processes. Additionally, QS inhibitors or quenchers may affect antibiotic susceptibility. Thus, targeting elements that regulate QS and biofilm formation might be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.

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“…RpoN has been shown to be important for stress and antibiotic resistance in other bacteria. For example, blocking RpoN has been found to increase susceptibility to several betalactam-based antibiotics in a laboratory strain of P. aeruginosa (Lloyd et al, 2019). The rpoN mutant of Campylobacter jejuni was more susceptible to acid stress; more resistant to H 2 O 2 ; and had little effect on the resistance to alkaline pH, heat, cold, and antimicrobials than the wild-type strain (Hwang et al, 2011).…”

Section: Antibioticsmentioning

confidence: 99%

Involvement of RpoN in Regulating Motility, Biofilm, Resistance, and Spoilage Potential of Pseudomonas fluorescens

Liu

Zhu

et al. 2021

Front. Microbiol.

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Pseudomonas fluorescens is a typical spoiler of proteinaceous foods, and it is characterized by high spoilage activity. The sigma factor RpoN is a well-known regulator controlling nitrogen assimilation and virulence in many pathogens. However, its exact role in regulating the spoilage caused by P. fluorescens is unknown. Here, an in-frame deletion mutation of rpoN was constructed to investigate its global regulatory function through phenotypic and RNA-seq analysis. The results of phenotypic assays showed that the rpoN mutant was deficient in swimming motility, biofilm formation, and resistance to heat and nine antibiotics, while the mutant increased the resistance to H2O2. Moreover, the rpoN mutant markedly reduced extracellular protease and total volatile basic nitrogen (TVB-N) production in sterilized fish juice at 4°C; meanwhile, the juice with the rpoN mutant showed significantly higher sensory scores than that with the wild-type strain. To identify RpoN-controlled genes, RNA-seq-dependent transcriptomics analysis of the wild-type strain and the rpoN mutant was performed. A total of 1224 genes were significantly downregulated, and 474 genes were significantly upregulated by at least two folds at the RNA level in the rpoN mutant compared with the wild-type strain, revealing the involvement of RpoN in several cellular processes, mainly flagellar mobility, adhesion, polysaccharide metabolism, resistance, and amino acid transport and metabolism; this may contribute to the swimming motility, biofilm formation, stress and antibiotic resistance, and spoilage activities of P. fluorescens. Our results provide insights into the regulatory role of RpoN of P. fluorescens in food spoilage, which can be valuable to ensure food quality and safety.

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Blocking RpoN reduces virulence of Pseudomonas aeruginosa isolated from cystic fibrosis patients and increases antibiotic sensitivity in a laboratory strain

Cited by 18 publications

References 54 publications

Decoding Genetic Features and Antimicrobial Susceptibility of Pseudomonas aeruginosa Strains Isolated from Bloodstream Infections

Decoding Genetic Features and Antimicrobial Susceptibility of Pseudomonas aeruginosa Strains Isolated from Bloodstream Infections

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Involvement of RpoN in Regulating Motility, Biofilm, Resistance, and Spoilage Potential of Pseudomonas fluorescens

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