The Bacterial Mfd Protein Prevents DNA Damage Induced by the Host Nitrogen Immune Response in a NER-Independent but RecBC-Dependent Pathway

Darrigo, Claire; Guillemet, Elisabeth; Dervyn, Rozenn; Ramarao, Nalini

doi:10.1371/journal.pone.0163321

Cited by 18 publications

(19 citation statements)

References 59 publications

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“…Archaeal Spt5, homologous to bacterially encoded NusG, consists of two domains: the NusG N-terminal (NGN) domain and a single C-terminal Kyrpides-Ouzounis-Woese (KOW) domain with affinity for single-stranded RNA (71,72,77); eukaryotic Spt5 typically contain three to six repeats of the C-terminal KOW domain (9,79,80). Critical, direct molecular interactions between Spt5 and RNAP have been identified in both Bacteria and Archaea, and the conservation of RNAP and Spt5 infers that these same interactions are used in Eukarya.…”

Section: Regulation Of Transcription Elongationmentioning

confidence: 99%

Factor-dependent archaeal transcription termination

Walker

Luyties

Santangelo

2017

Proc. Natl. Acad. Sci. U.S.A.

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We demonstrate that binding of the conserved and essential archaeal transcription factor TFE to the archaeal RNAP is directed, in part, by interactions with the RpoE subunit of RNAP. As the surfaces involved are conserved in many eukaryotic and archaeal systems, the identified TFE-RNAP interactions are likely conserved in archaeal-eukaryal systems and represent an important point of contact that can influence the efficiency of transcription initiation.While many studies in archaea have focused on elucidating the mechanism of transcription initiation and elongation, studies on termination were slower to emerge.Transcription factors promoting initiation and elongation have been characterized in each Domain but transcription termination factors have only been identified in bacteria and eukarya.Here we characterize the first archaeal termination factor (termed Eta) capable of disrupting the transcription elongation complex, detail the rate of and requirements for Eta-mediated transcription termination and describe a role for Eta in transcription termination in vivo. Etamediated transcription termination is energy-dependent, requires upstream DNA sequences and disrupts transcription elongation complexes to release the nascent RNA to solution. Deletion of TK0566 (encoding Eta) is possible, but results in slow growth and renders cells sensitive to iii DNA damaging agents. Structure-function studies reveal that the N-terminal domain of Eta is not necessary for Eta-mediated termination in vitro, but Thermococcus kodakarensis cells lacking the N-terminal domain exhibit slow growth compared to parental strains. We report the first crystal structure of Eta that will undoubtedly lead to further structure-function analyses. The results obtained argue that the mechanisms employed by termination factors in archaea, eukarya, and bacteria to disrupt the transcription elongation complex may be conserved and that Eta stimulates release of stalled or arrested transcription elongation complexes.iv ACKNOWLEDGEMENTS

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Section: Regulation Of Transcription Elongationmentioning

confidence: 99%

Factor-dependent archaeal transcription termination

Walker

Luyties

Santangelo

2017

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, they are important for the infectivity and pathogenicity of bacteria that need to resist oxidative and nitrosative attack from neutrophils and macrophages (Amundsen et al, 2008; Darrigo et al, 2016; Amundsen et al, 2009; Cano et al, 2002). They protect cells from antibacterials that cause DSBs, such as ciprofloxacin, because they afford a basal level of protection against such damage (Amundsen et al, 2009; Henderson and Kreuzer, 2015; González-Soltero et al, 2015; Tamae et al, 2008; McDaniel et al, 1978).…”

Section: Introductionmentioning

confidence: 99%

Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones

Wilkinson

Troman

Ismah

et al. 2016

eLife

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Our previous paper (Wilkinson et al, 2016) used high-resolution cryo-electron microscopy to solve the structure of the Escherichia coli RecBCD complex, which acts in both the repair of double-stranded DNA breaks and the degradation of bacteriophage DNA. To counteract the latter activity, bacteriophage λ encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate. We also show that expression of Gam in E. coli or Klebsiella pneumoniae increases sensitivity to fluoroquinolones; antibacterials that kill cells by inhibiting topoisomerases and inducing double-stranded DNA breaks. Furthermore, fluoroquinolone-resistance in K. pneumoniae clinical isolates is reversed by expression of Gam. Together, our data explain the synthetic lethality observed between topoisomerase-induced DNA breaks and the RecBCD gene products, suggesting a new co-antibacterial strategy.DOI: http://dx.doi.org/10.7554/eLife.22963.001

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“…This implies that the bacteria have developed means to resist to the inflammatory cells and thus to the host immune system. We have consistently shown that B. cereus is able to circumvent the host immune response ( Tran and Ramarao, 2013 ; Darrigo et al, 2016 ; Guillemet et al, 2016 ). B. cereus spores survive, germinate, and multiply in contact with macrophages ( Ramarao and Lereclus, 2005 ), eventually leading to the production of toxins responsible for macrophage death ( Tran et al, 2011a , b ; Ramarao and Sanchis, 2013 ).…”

Section: Discussionmentioning

confidence: 82%

InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages

et al. 2018

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Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation in the host despite the induction of inflammation. To circumvent inflammation, bacteria must resist the bactericidal activity of professional phagocytes, which constitute a first line of host defense against pathogens. Interactions between phagocytic cells and B. cereus are still poorly characterized and the mechanism of resistance to the host immune system is not known yet. We have previously shown that the spores are phagocytosed by macrophages but survive and escape from these cells. The metalloprotease InhA1 is a key effector involved in these processes. inhA1-deficient spores are retained intracellularly, in contrast to the wild type strain spores. NprA is also a B. cereus metalloprotease able to cleave tissue components such as fibronectin, laminin, and collagen. Here, we show that NprA, concomitantly secreted with InhA1 in the B. cereus secretome, is essential to promote bacterial escape from macrophages. We show that InhA1 cleaves NprA at specific sites. This cleavage allows liberation of the mature form of the NprA protein in the supernatant of the wild type strain. This mature form of NprA is actually the principal effector allowing bacterial escape from host macrophages.

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The Bacterial Mfd Protein Prevents DNA Damage Induced by the Host Nitrogen Immune Response in a NER-Independent but RecBC-Dependent Pathway

Cited by 18 publications

References 59 publications

Factor-dependent archaeal transcription termination

Factor-dependent archaeal transcription termination

Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones

InhA1-Mediated Cleavage of the Metalloprotease NprA Allows Bacillus cereus to Escape From Macrophages

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