Structural and functional analysis of the Francisella lysine decarboxylase as a key actor in oxidative stress resistance

Félix, Jan; Siebert, Claire; Ducassou, Julia Novion; Nigou, Jérôme; Garcia, Pierre; Fraudeau, Angélique; Huard, Karine; Mas, Caroline; Brochier-Armanet, Céline; Couté, Yohann; Gutsche, Irina; Renesto, Patricia

doi:10.1038/s41598-020-79611-5

Cited by 10 publications

(7 citation statements)

References 93 publications

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“…We propose that the reduced content in UQ in the Tn-ubiC Fn mutant could therefore affect F. novicida's oxidative defense. This hypothesis is in good agreement with recent data showing that reduced expression of UbiC Fn decreases the resistance of F. novicida to oxidative stress (44).…”

Section: Discussionsupporting

confidence: 93%

The Biosynthetic Pathway of Ubiquinone Contributes to Pathogenicity of Francisella novicida

et al. 2021

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Francisella tularensis is the causative agent of tularemia. Because of its extreme infectivity and high mortality rate, this pathogen was classified as a biothreat agent. Francisella spp are strict aerobe and ubiquinone (UQ) has been previously identified in these bacteria. While the UQ biosynthetic pathways were extensively studied in Escherichia coli allowing the identification of fifteen Ubi-proteins to date, little is known about Francisella spp. In this study, and using Francisella novicida as a surrogate organism, we first identified UQ 8 as the major quinone found in the membranes of this bacterium. Then, we characterized the UQ biosynthetic pathway in F. novicida using a combination of bioinformatics, genetics and biochemical approaches. Our analysis disclosed the presence in Francisella of ten putative Ubi-proteins and we confirmed eight of them by heterologous complementation in E. coli . The UQ biosynthetic pathways from F. novicida and E. coli share a similar pattern. However, differences were highlighted: the decarboxylase remains unidentified in Francisella spp and homologs of the Ubi-proteins involved in the O 2 -independent UQ pathway are not present. This is in agreement with the strictly aerobic niche of this bacterium. Then, via two approaches, i.e. the use of an inhibitor (3-amino-4-hydroxybenzoic acid) and a transposon mutant, which both strongly impair the synthesis of UQ, we demonstrated that UQ is essential for the growth of F. novicida in a respiratory medium and contributes to its pathogenicity in Galleria mellonella used as an alternative animal model. Importance Francisella tularensis is the causative bacterium of tularemia and is classified as a biothreat agent. Using multidisciplinary approaches, we investigated the ubiquinone (UQ) biosynthetic pathway that operates in F. novicida used as a surrogate. We showed that UQ 8 is the major quinone identified in the membranes of Francisella novicida . We identified a new competitive inhibitor, which strongly decreased the biosynthesis of UQ. Our demonstration of the crucial role of UQ for the respiratory metabolism of F. novicida and for the involving in its pathogenicity in the Galleria mellonella model should stimulate the search for selective inhibitors of bacterial UQ biosynthesis.

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Section: Discussionsupporting

confidence: 93%

The Biosynthetic Pathway of Ubiquinone Contributes to Pathogenicity of Francisella novicida

et al. 2021

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“…Color blocks represent similar enzymatic activities. Confirmation of enzymatic activity and gene identity: FratuLDCc-w ( 28 ), EscoLDCc-w ( 20 , 72 ), EscoLDCi-w ( 73 ), PseaeLDCc-w ( 26 ), RalstODCc-w ( 74 ), BoperODCc-w ( 75 ), LabacODCi-w ( 76 ), OeoenODCi-w ( 77 ), StepiODCi-w ( 78 ), StlugODCi-w ( 79 ), EscoODCc-w ( 80 ), EscoODCi-w ( 81 ), CldifADC-a ( 22 ), SerumADC-a ( 30 ), StpneADC-a ( 31 ), BasubADC-a ( 21 ). From the current study, CaexiODC-a, Lefer LDC-a, MeblaADC-a, PsychADC-a, HutheADC-a, PesimADC-a, BacihADC-a, ClbotODC-a, ThtheOLDC-a, FunucODC-aa, FunecODC-a.…”

Section: Resultsmentioning

confidence: 99%

“…Extended-form ADC/ODC/LDC are found extensively in Proteobacteria and some Firmicutes, whereas aADC has been functionally identified only in the Firmicutes. The basic structure of the extended decarboxylases is a dimer of identical monomers, and the N-terminal REC domain is required for formation of a decameric form (a pentameric ring of dimers) in acid-inducible exADC ( 23 ) and exLDC ( 13 , 24 ), in constitutive exLDC ( 25 , 26 , 27 , 28 ), and a dodecameric form in Lactobacillus exODC ( 29 ). The functionally characterized aADCs from firmicute species are found in B. subtilis ( 21 , 22 ), S. ruminantium ( 30 ), Clostridioides difficile ( 22 ), and Streptococcus pneumoniae ( 31 ).…”

mentioning

confidence: 99%

Discovery of ancestral L-ornithine and L-lysine decarboxylases reveals parallel, pseudoconvergent evolution of polyamine biosynthesis

Liang

Hanfrey

et al. 2021

Journal of Biological Chemistry

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Polyamines are fundamental molecules of life, and their deep evolutionary history is reflected in extensive biosynthetic diversification. The polyamines putrescine, agmatine, and cadaverine are produced by pyridoxal 5′-phosphate-dependent L-ornithine, L-arginine, and L-lysine decarboxylases (ODC, ADC, LDC), respectively, from both the alanine racemase (AR) and aspartate aminotransferase (AAT) folds. Two homologous forms of AAT-fold decarboxylase are present in bacteria: an ancestral form and a derived, acid-inducible extended form containing an N-terminal fusion to the receiver-like domain of a bacterial response regulator. Only ADC was known from the ancestral form and limited to the Firmicutes phylum, whereas extended forms of ADC, ODC, and LDC are present in Proteobacteria and Firmicutes. Here, we report the discovery of ancestral form ODC, LDC, and bifunctional O/LDC and extend the phylogenetic diversity of functionally characterized ancestral ADC, ODC, and LDC to include phyla Fusobacteria, Caldiserica, Nitrospirae, and Euryarchaeota. Using purified recombinant enzymes, we show that these ancestral forms have a nascent ability to decarboxylate kinetically less preferred amino acid substrates with low efficiency, and that product inhibition primarily affects preferred substrates. We also note a correlation between the presence of ancestral ODC and ornithine/arginine auxotrophy and link this with a known symbiotic dependence on exogenous ornithine produced by species using the arginine deiminase system. Finally, we show that ADC, ODC, and LDC activities emerged independently, in parallel, in the homologous AAT-fold ancestral and extended forms. The emergence of the same ODC, ADC, and LDC activities in the nonhomologous AR-fold suggests that polyamine biosynthesis may be inevitable.

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“…For example, O'Brien et al analyzed a respiratory pathogen S. pneumoniae , which causes about 1 million deaths per year worldwide, by genome and transcriptome studies to predict the mechanism of antibiotic resistance as well as in vivo infection conditions (O’Brien et al, 2009 ). Proteomics combined with genomics was used to analyze different lineages of Mycobacterium tuberculosis (Yimer et al, 2020 ) and in a separate study (Felix et al, 2021 ) Francisella tularensis , a pathogen causing the acute human respiratory disease tularemia, to decipher the virulence factors and infection mechanisms in these pathogens. Similarly, Agostini et al applied genomics, proteomics, and metabolomics in concert to identify the adaptive mechanism of E. coli to fluorinated indoles (Agostini et al, 2021 ).…”

Section: Analytical Methods For Bacterial Adaptive Evolutionmentioning

confidence: 99%

Microbial adaptive evolution

Shi

Feng

Broach

2021

Journal of Industrial Microbiology and Biotechnology

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Bacterial species can adapt to significant changes in their environment by mutation followed by selection, a phenomenon known as adaptive evolution. With the development of bioinformatics and genetic engineering, research on adaptive evolution has progressed rapidly, as have applications of the process. In this review, we summarize various mechanisms of bacterial adaptive evolution, the technologies used for studying it and successful applications of the method in research and industry. We particularly highlight the contributions of Dr. L.O. Ingram. Microbial adaptive evolution has significant impact on our society not only from its industrial applications but also in the evolution, emergence and control of various pathogens.

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Structural and functional analysis of the Francisella lysine decarboxylase as a key actor in oxidative stress resistance

Cited by 10 publications

References 93 publications

The Biosynthetic Pathway of Ubiquinone Contributes to Pathogenicity of Francisella novicida

The Biosynthetic Pathway of Ubiquinone Contributes to Pathogenicity of Francisella novicida

Discovery of ancestral L-ornithine and L-lysine decarboxylases reveals parallel, pseudoconvergent evolution of polyamine biosynthesis

Microbial adaptive evolution

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