Neisseria gonorrhoeae: DNA Repair Systems and Their Role in Pathogenesis

Savitskaya, Viktoriia Yu.; Monakhova, Mayya V.; Iakushkina, Iuliia V.; Borovikova, Irina I.; Кубарева, Е. А.

doi:10.1134/s0006297922090097

Cited by 2 publications

(5 citation statements)

References 130 publications

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“…One of several hypotheses explaining the effect of MMR on the frequency of pilin variation is the regulation of homologous recombination through the interaction of MMR proteins with the G4 structure associated with the pilE promoter [ 22 ]. While G4-binding activity is well known for ngMutS [ 20 ], it has not previously been shown for ngMutL. The main goal of our study was to examine the ability of the ngMutL protein to specifically bind pilE G4 and to understand whether the G4 structure affects the recombination-associated endonuclease activity of ngMutL.…”

Section: Discussionmentioning

confidence: 99%

“…MMR is a post replicative system, conserved in prokaryotes and eukaryotes, that repairs base pair mismatches and small insertion-deletion loops that occur after DNA replication or recombination. The key proteins of MMR from N. gonorrhoeae are MutS and MutL, denoted as ngMutS and ngMutL, respectively [ 20 ]. ngMutS recognizes the DNA mismatch and recruits the ngMutL endonuclease, which makes a single-stranded break in the DNA daughter strand, initiating the repair process.…”

Section: Introductionmentioning

confidence: 99%

“…ngMutS recognizes the DNA mismatch and recruits the ngMutL endonuclease, which makes a single-stranded break in the DNA daughter strand, initiating the repair process. Like other DNA repair pathways such as base or nucleotide excision repair, MMR is critically important for N. gonorrhoeae because it is able to correct pilE / pilS recombination events [ 20 ]. Criss et al showed that the absence of MMR or inactivation of the ngMutS protein increased the frequency of pilin antigenic variations and, accordingly, antibiotic resistance, virulence, and adhesion to epithelial cells [ 19 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…There are several hypotheses that explain the effect of MMR on the frequency of pilin variation. The most popular is the accumulation of mutations due to MMR inactivation [ 20 ]. The alternative is the involvement of MMR proteins in initiating pilin antigenic variation through interaction with the G4 structure located upstream of the pilE promoter [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway

Savitskaya

Strekalovskikh

Snyga

et al. 2023

IJMS

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The human pathogen Neisseria gonorrhoeae uses a homologous recombination to undergo antigenic variation and avoid an immune response. The surface protein pilin (PilE) is one of the targets for antigenic variation that can be regulated by N. gonorrhoeae mismatch repair (MMR) and a G-quadruplex (G4) located upstream of the pilE promoter. Using bioinformatics tools, we found a correlation between pilE variability and deletion of DNA regions encoding ngMutS or ngMutL proteins, the main participants in N. gonorrhoeae methyl-independent MMR. To understand whether the G4 structure could affect the ngMutL-mediated regulation of pilin antigenic variation, we designed several synthetic pilE G4-containing oligonucleotides, differing in length, and related DNA duplexes. Using CD measurements and biochemical approaches, we have showed that (i) ngMutL preferentially binds to pilE G4 compared to DNA duplex, although the latter is a cognate substrate for ngMutL endonuclease, (ii) protein binding affinity decreases with shortening of quadruplex-containing and duplex ligands, (iii) the G4 structure inhibits ngMutL-induced DNA nicking and modulates cleavage positions; the enzyme does not cleave DNA within G4, but is able to bypass this noncanonical structure. Thus, pilE G4 may regulate the efficiency of pilin antigenic variation by quadruplex binding to ngMutL and suppression of homologous recombination.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway

Savitskaya

Strekalovskikh

Snyga

et al. 2023

IJMS

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“…CT is an intracellular pathogen with an infection rate of 9.8% ( 8 , 9 ) and of various serotypes ( 10 ). NG is the only one among the three pathogens that can be observed under the microscope by gram staining ( 11 ) and usually causes urethritis and cervicitis ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Characteristics of common pathogens of urogenital tract among outpatients in Shanghai, China from 2016 to 2021

Wang,

Ding,

Liu

et al. 2023

Front. Public Health

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BackgroundUreaplasma urealyticum, Chlamydia trachomatis, and Neisseria gonorrhoeae are the prevalent causes of several genital diseases worldwide; however, their characteristics in different genders have not been well documented in Shanghai. The aim of this study is to describe the prevalence of common pathogens among outpatients, considering variations by gender and age.MethodsFrom January 1, 2016, to December 31, 2021, the urogenital swabs of 16216 outpatients aged 3–95 years from two general hospitals in Shanghai were collected. All participants' swabs were investigated for U. urealyticum, C. trachomatis, and N. gonorrhoeae by isothermal RNA-based simultaneous amplification and testing. The basic information of all participants was also recorded, including age and gender. The chi-square test was used to compare the prevalence between different genders, age groups, and infection patterns.ResultsThere were 5,744 patients (35.42%) with positive samples whose ages ranged from 7 to 80 years (33.23 ± 8.63 years), and 62.14% of them were women. The most common pathogen detected was U. urealyticum (85.08%). The highest prevalence rate of all three pathogens was found in patients aged ≤ 20 years (40.53%, 95% confidence intervals [CI]: 33.80%-47.63%). The prevalent rate of U. urealyticum was higher in men (33.36%, 95% CI: 32.19%-34.55%). The overall prevalence rates of U. urealyticum, C. trachomatis, and N. gonorrhoeae were 30.14% (95% CI: 29.44%-30.85%), 6.00% (95% CI: 5.64%-6.38%), and 2.10% (95% CI: 1.89%-2.33%).ConclusionsUreaplasma urealyticum was the most prevalent pathogen in the population, and its prevalence decreased with age. Young men aged ≤ 20 years were more frequently infected. Regular screening for sexually transmitted pathogens in different genders and age groups are warranted, particularly in young men.

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Neisseria gonorrhoeae: DNA Repair Systems and Their Role in Pathogenesis

Cited by 2 publications

References 130 publications

pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway

pilE G-Quadruplex Is Recognized and Preferentially Bound but Not Processed by the MutL Endonuclease from Neisseria gonorrhoeae Mismatch Repair Pathway

Characteristics of common pathogens of urogenital tract among outpatients in Shanghai, China from 2016 to 2021

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