Molybdate transporter ModABC is important for Pseudomonas aeruginosa chronic lung infection

Périnet, Simone; Jeukens, Julie; Kukavica-Ibrulj, Iréna; Ouellet, Myriam; Charette, Steve J.; Levesque, Roger C.

doi:10.1186/s13104-016-1840-x

Cited by 19 publications

(37 citation statements)

References 49 publications

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“…This gene cluster is involved in the biosynthesis of the molybdenum cofactor, which is needed for the activity of all nitrate reductases 29 . This decreased expression was also linked to a lower expression of the modA gene involved in molybdenum acquisition 30 . These alterations suggest that decreased Nar-dependent generation of ATP might contribute to the mutant growth defect at least in anaerobic but probably not in aerobic conditions, in which the transcriptomic and proteomic analysis were carried out.…”

Section: Resultsmentioning

confidence: 96%

The absence of SigX results in impaired carbon metabolism and membrane fluidity in Pseudomonas aeruginosa

Fléchard

Duchesne

Tahrioui

et al. 2018

Sci Rep

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In Pseudomonas aeruginosa, SigX is an extra-cytoplasmic function σ factor that belongs to the cell wall stress response network. In previous studies, we made the puzzling observation that sigX mutant growth was severely affected in rich lysogeny broth (LB) but not in minimal medium. Here, through comparative transcriptomic and proteomic analysis, we show that the absence of SigX results in dysregulation of genes, whose products are mainly involved in transport, carbon and energy metabolisms. Production of most of these genes is controlled by carbon catabolite repression (CCR), a key regulatory system than ensures preferential carbon source uptake and utilization, substrate prioritization and metabolism. The strong CCR response elicited in LB was lowered in a sigX mutant, suggesting altered nutrient uptake. Since the absence of SigX affects membrane composition and fluidity, we suspected membrane changes to cause such phenotype. The detergent polysorbate 80 (PS80) can moderately destabilize the envelope resulting in non-specific increased nutrient intake. Remarkably, growth, membrane fluidity and expression of dysregulated genes in the sigX mutant strain were restored in LB supplemented with PS80. Altogether, these data suggest that SigX is indirectly involved in CCR regulation, possibly via its effects on membrane integrity and fluidity.

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Section: Resultsmentioning

confidence: 96%

The absence of SigX results in impaired carbon metabolism and membrane fluidity in Pseudomonas aeruginosa

Fléchard

Duchesne

Tahrioui

et al. 2018

Sci Rep

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“…The increase in nitrate and molybdate ABC transporters in P. aeruginosa exposed to Co-culture CuF indicate anaerobic growth. Molybdate is required for the formation of molybdoenzymes such as nitrate reductases, which are essential for the use of nitrates during anaerobic respiration [48], so much so, that mutants for molybdate ABC transporters (ModABC) are unable to grow anaerobically and are less virulent under aerobic and anaerobic conditions [49].…”

Section: Discussionmentioning

confidence: 99%

The Aspergillus fumigatus Secretome Alters the Proteome of Pseudomonas aeruginosa to Stimulate Bacterial Growth: Implications for Co-infection

Margalit

Carolan

Sheehan

et al. 2020

Molecular & Cellular Proteomics

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Individuals with cystic fibrosis are susceptible to co-infection by Aspergillus fumigatus and Pseudomonas aeruginosa. Despite the persistence of A. fumigatus in the cystic fibrosis lung P. aeruginosa eventually predominates as the primary pathogen. Several factors are likely to facilitate P. aeruginosa colonization in the airways, including alterations to the microbial environment. The cystic fibrosis airways are hypoxic, nitrate-rich environment, and the sputum has higher amino acid concentrations than normal. In this study, significant growth proliferation was observed in P. aeruginosa when the bacteria were exposed to A. fumigatus culture filtrates (CuF) containing a high nitrate content. Proteomic analysis of the A. fumigatus CuF identified a significant number of environment-altering proteases and peptidases. The molecular mechanisms promoting bacterial growth were investigated using Label-free quantitative (LFQ) proteomics to compare the proteome of P. aeruginosa grown in the A. fumigatus CuF and in CuF produced by a P. aeruginosa-A. fumigatus Co-culture, to that cultured in P. aeruginosa CuF. LFQ proteomics revealed distinct changes in the proteome of P. aeruginosa when cultured in the different CuF, including increases in the levels of proteins involved in denitrification, stress response, replication, amino acid metabolism and efflux pumps, and a downregulation of pathways involving ABC transporters. These findings offer novel insights into the complex dynamics that exist between P. aeruginosa and A. fumigatus. Understanding the molecular strategies that enable P. aeruginosa to predominate in an environment where A. fumigatus exists is important in the context of therapeutic development to target this pathogen.

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“…Molybdate is the oxyanion form of molybdenum, an important metal cofactor for many molybdoenzymes involved in carbon, sulphur, and nitrogen metabolism . In Pseudomonas aeruginosa and Mycobacterium tuberculosis , molybdenum and the ModABC transport system have been implicated in virulence such as biofilm formation and intracellular survival in macrophages . It is possible that molybdenum may also be important for B. pertussis virulence.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Adaptation of Australian Epidemic Bordetella pertussis

et al. 2018

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Bordetella pertussis causes whooping cough. The predominant strains in Australia changed to single nucleotide polymorphism (SNP) cluster I (pertussis toxin promoter allele ptxP3/pertactin gene allele prn2) from cluster II (non-ptxP3/non-prn2). Cluster I was mostly responsible for the 2008-2012 Australian epidemic and was found to have higher fitness compared to cluster II using an in vivo mouse competition assay, regardless of host's immunization status. This study aimed to identify proteomic differences that explain higher fitness in cluster I using isobaric tags for relative and absolute quantification (iTRAQ), and high-resolution multiple reaction monitoring (MRM-hr). A few key differences in the whole cell and secretome were identified between the cluster I and II strains tested. In the whole cell, nine proteins were upregulated (>1.2 fold change, q < 0.05) and three were downregulated (<0.8 fold change, q < 0.05) in cluster I. One downregulated protein was BP1569, a TLR2 agonist for Th1 immunity. In the secretome, 12 proteins were upregulated and 1 was downregulated which was Bsp22, a type III secretion system (T3SS) protein. Furthermore, there was a trend of downregulation in three T3SS effectors and other virulence factors. Three proteins were upregulated in both whole cell and supernatant: BP0200, molybdate ABC transporter (ModB), and tracheal colonization factor A (TcfA). Important expression differences in lipoprotein, T3SS, and transport proteins between the cluster I and II strains were identified. These differences may affect immune evasion, virulence and metabolism, and play a role in increased fitness of cluster I.

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Molybdate transporter ModABC is important for Pseudomonas aeruginosa chronic lung infection

Cited by 19 publications

References 49 publications

The absence of SigX results in impaired carbon metabolism and membrane fluidity in Pseudomonas aeruginosa

The absence of SigX results in impaired carbon metabolism and membrane fluidity in Pseudomonas aeruginosa

The Aspergillus fumigatus Secretome Alters the Proteome of Pseudomonas aeruginosa to Stimulate Bacterial Growth: Implications for Co-infection

Proteomic Adaptation of Australian Epidemic Bordetella pertussis

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