A Thermonuclease of<i>Neisseria gonorrhoeae</i>Enhances Bacterial Escape From Killing by Neutrophil Extracellular Traps

Juneau, Richard A.; Stevens, Jacqueline S.; Apicella, Michael A.; Criss, Alison K.

doi:10.1093/infdis/jiv031

Cited by 65 publications

(62 citation statements)

References 34 publications

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“…The failure to detect Nuc or its DNA-degrading activity in the supernatant led to the suggestion that Nuc may be localized in the periplasm (8). In a recent study, Nuc was found to have extracellular activity, but it remained unclear whether extracellular Nuc arose through secretion or through lysis (9). The fact that Nuc contains an N-terminal signal peptide supports the idea that Nuc resides within the periplasm at least transiently.…”

Section: Discussionmentioning

confidence: 99%

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Single-Stranded DNA Uptake during Gonococcal Transformation

et al. 2016

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Neisseria gonorrhoeae is naturally competent for transformation. The first step of the transformation process is the uptake of DNA from the environment into the cell. This transport step is driven by a powerful molecular machine. Here, we addressed the question whether this machine imports single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) at similar rates. The fluorescence signal associated with the uptake of short DNA fragments labeled with a single fluorescent marker molecule was quantified. We found that ssDNA with a double-stranded DNA uptake sequence (DUS) was taken up with a similar efficiency as dsDNA. Imported ssDNA was degraded rapidly, and the thermonuclease Nuc was required for degradation. In a nuc deletion background, dsDNA and ssDNA with a double-stranded DUS were imported and used as the substrates for transformation, whereas the import and transformation efficiencies of ssDNA with single-stranded DUS were below the detection limits. We conclude that the DNA uptake machine requires a double-stranded DUS for efficient DNA recognition and transports ssDNA and dsDNA with comparable efficiencies. IMPORTANCEBacterial transformation enables bacteria to exchange genetic information. It can speed up adaptive evolution and enhances the potential of DNA repair. The transport of DNA through the outer membrane is the first step of transformation in Gram-negative species. It is driven by a powerful molecular machine whose mechanism remains elusive. Here, we show for Neisseria gonorrhoeae that the machine transports single-and double-stranded DNA at comparable rates, provided that the species-specific DNA uptake sequence is double stranded. Moreover, we found that single-stranded DNA taken up into the periplasm is rapidly degraded by the thermonuclease Nuc. We conclude that the secondary structure of transforming DNA is important for the recognition of self DNA but not for the process of transport through the outer membrane.

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Section: Discussionmentioning

confidence: 99%

“…Methylation of gonococcal chromosomal DNA limits Nuc's activity. Moreover, Nuc can degrade neutrophil extracellular traps (9). While Nuc carries a signal peptide for secretion, active secretion into the supernatant has not been observed, and therefore, a periplasmic location was proposed (8).…”

mentioning

confidence: 99%

Single-Stranded DNA Uptake during Gonococcal Transformation

et al. 2016

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“…Seper and colleagues (38) found that a Vibrio cholerae strain deficient for two extracellular nucleases, deoxyribonuclease and xds, was less invasive than wild-type V. cholerae in immunocompetent mice, although no difference between strains was seen in neutropenic mice, and quantitative RT-PCR revealed that the presence of either NETs or DNA was able to up-regulate the expression of deoxyribonuclease and xds (38). Neisseria gonorrheae has also been shown to encode the heat-stable nuclease, nuc, thought to be important for remodeling N. gonorrheae biofilms (39). NETs were shown to be rapidly induced by N. gonorrheae, but thereafter NET integrity decreased over time in nuccontaining strains compared with a Dnuc mutant, as measured by Sytox Green immunofluorescence.…”

Section: Other Pathogens: Net Degradationmentioning

confidence: 99%

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens

Storisteanu¹,

Pocock²,

Cowburn

et al. 2017

Am J Respir Cell Mol Biol

101

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The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histoneand protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction, and chronic obstructive pulmonary disease. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae, and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as an immune protection strategy among respiratory pathogens, including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae, has been growing, with the majority of these studies being published in the past 2 years. Evasion strategies fall into three main categories: inhibition of NET release by down-regulating host inflammatory responses; degradation of NETs using pathogen-derived DNases; and resistance to the microbicidal components of NETs, which involves a variety of mechanisms, including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article outlines the evidence supporting the three main strategies of NET evasion-inhibition, degradation, and resistance-with particular reference to common respiratory pathogens.

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“…periodontopathogenic bacteria can produce extracellular nucleases (367,375). Recently, it was determined that Neisseria gonorrhoeae encodes for a heat-stable thermonuclease (Nuc), which provides the bacterium an effective virulence factor against NETs, as it is capable of DNA degradation (396). After NETs were produced, the presence of thermonuclease aided the bacterium in degrading the DNA and enhancing their survival capabilities (396).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was determined that Neisseria gonorrhoeae encodes for a heat-stable thermonuclease (Nuc), which provides the bacterium an effective virulence factor against NETs, as it is capable of DNA degradation (396). After NETs were produced, the presence of thermonuclease aided the bacterium in degrading the DNA and enhancing their survival capabilities (396). No significant reduction in NET formation when NETs stimulated with PMA are then exposed to F. alocis broth or growth supernatant (data not shown) which suggests that although F. alocis possesses a thermonuclease, it may be present at a low concentration, therefore deeming it ineffective in degradation of NETs.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Armstrong¹

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A Thermonuclease ofNeisseria gonorrhoeaeEnhances Bacterial Escape From Killing by Neutrophil Extracellular Traps

Cited by 65 publications

References 34 publications

Single-Stranded DNA Uptake during Gonococcal Transformation

Single-Stranded DNA Uptake during Gonococcal Transformation

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

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