The threat of untreatable gonorrhoea: implications and consequences for reproductive and sexual morbidity

Ndowa, Francis; Narasimhan, Manjulaa

doi:10.1016/s0968-8080(12)40653-x

Cited by 35 publications

(24 citation statements)

References 29 publications

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“…Gonorrhea remains a major public health concern due to increasing Gc resistance to antibiotics, lack of protective immunity from prior infection, and no protective vaccine (2,3). The inflammatory response associated with gonorrhea leads to serious complications such as pelvic inflammatory disease and infertility (4).…”

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Assembly of NADPH Oxidase in Human Neutrophils Is Modulated by the Opacity-Associated Protein Expression State of Neisseria gonorrhoeae

2014

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Neisseria gonorrhoeae (the gonococcus, Gc) triggers a potent inflammatory response and recruitment of neutrophils to the site of infection. Gc survives exposure to neutrophils despite these cells' antimicrobial products, such as reactive oxygen species (ROS). ROS production in neutrophils is initiated by NADPH oxidase, which converts oxygen into superoxide. The subunits of NADPH oxidase are spatially separated between granules (gp91 phox /p22 phox ) and the cytoplasm (p47 phox , p67 phox , and p40 phox ). Activation of neutrophils promotes the coassembly of NADPH oxidase subunits at phagosome and/or plasma membranes. While Gc-expressing opacity-associated (Opa) proteins can induce neutrophils to produce ROS, Opa-negative (Opa ؊ ) Gc does not stimulate neutrophil ROS production. Using constitutively Opa ؊ and OpaD-positive (OpaD ؉ ) Gc bacteria in strain FA1090, we now show that the difference in ROS production levels in primary human neutrophils between these backgrounds can be attributed to differential assembly of NADPH oxidase. Neutrophils infected with Opa ؊ Gc showed limited translocation of NADPH oxidase cytoplasmic subunits to cellular membranes, including the bacterial phagosome. In contrast, these subunits rapidly translocated to neutrophil membranes following infection with OpaD ؉ Gc. gp91 phox and p22 phox were recruited to Gc phagosomes regardless of bacterial Opa expression. These results suggest that Opa ؊ Gc interferes with the recruitment of neutrophil NADPH oxidase cytoplasmic subunits to membranes, in particular, the p47 phox "organizing" subunit, to prevent assembly of the holoenzyme, resulting in an absence of the oxidative burst.

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Assembly of NADPH Oxidase in Human Neutrophils Is Modulated by the Opacity-Associated Protein Expression State of Neisseria gonorrhoeae

2014

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“…N eisseria gonorrhoeae infection is often seen in male urethritis and female cervicitis, and its diagnosis has historically led to prompt initiation of treatments with a single antibiotic (1,2). In the 1990s in most Asian countries, fluoroquinolones (FQs) were often used for this infection, partly because FQs have higher concentrations in the urinary tract.…”

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Azithromycin Resistance and Its Mechanism in Neisseria gonorrhoeae Strains in Hyogo, Japan

Shigemura

Osawa

Miura

et al. 2015

Antimicrob Agents Chemother

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e Therapeutic options are limited for Neisseria gonorrhoeae infection, especially for oral drugs. The purpose of this study was to investigate the susceptibility of N. gonorrhoeae to oral azithromycin (AZM) and the correlation between AZM resistance-related gene mutations and MIC. We examined the AZM MICs of clinical strains of N. gonorrhoeae, sequenced the peptidyltransferase loop in domain V of 23S rRNA, and investigated the statistical correlation between AZM MIC and the presence and number of the mutations. Among 59 N. gonorrhoeae strains, our statistical data showed that a deletion mutation was seen significantly more often in the higher-MIC group (0.5 g/ml or higher) (35/37; 94.6%) than in the lower-MIC group (0.25 g/ml or less) (4/ 22; 18.2%) (P < 0.0001). However, a mutation of codon 40 (Ala¡Asp) in the mtrR gene (helix-turn-helix) was seen significantly more often in the lower-MIC group (12/22; 54.5%) (P < 0.0001). In N. gonorrhoeae multiantigen sequence typing (NG-MAST) analyses, ST4777 was representative of the lower-MIC group and ST1407, ST6798, and ST6800 were representative of the higher-MIC group. NG-MAST type 1407 was detected as the most prevalent type in AZM-resistant or -intermediate strains, as previously described. In conclusion, a deletion mutation in the mtrR promoter region may be a significant indicator for higher MIC (0.5 g/ml or higher). ST4777 was often seen in the lower-MIC group, and ST1407, ST6798, and ST6800 were characteristic of the higher-MIC group. Further research with a greater number of strains would help elucidate the mechanism of AZM resistance in N. gonorrhoeae infection.

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“…Bezüglich der Bedingungen, unter denen die Platten bis zur Ablese inkubiert beziehungsweise bebrütet werden, gaben 98,6 % der Labore eine Temperatur von 36 ± 1 °C an, die restlichen LaboAbb. 1 8 Räumliche Verteilung der teilnehmenden Labore mit NG-Diagnostik nach der Teilnahmebereitschaft an der zweiten Phase des GORENET-Projekts (blau = teilnahmebereit (100); grün = nicht teilnahmebereit (n = 188)) re gaben Werte von bis zu 37,5 °C an. Mit Ausnahme eines Labors, lagen alle Labore mit ihren Angaben hinsichtlich einer erhöhten CO 2 -Spannung im Bereich von 4,5-10 %.…”

Section: Diagnostikmethoden Und Qualität Von Kulturnachweisenunclassified

“…Bei Gonorrhö (GO) handelt es sich um eine Infektionskrankheit mit teilweise schwerwiegenden Folgen sowohl auf individueller als auch auf Public-HealthEbene [1][2][3][4][5]. Infektionen mit dem Erreger Neisseria gonorrhoeae (NG) äußern sich unter anderem als Urethritis oder Zervizitis und können vor allem hinsichtlich der reproduktiven Gesundheit schwerwiegende Folgen haben [1].…”

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“…Infektionen mit dem Erreger Neisseria gonorrhoeae (NG) äußern sich unter anderem als Urethritis oder Zervizitis und können vor allem hinsichtlich der reproduktiven Gesundheit schwerwiegende Folgen haben [1]. Gleichzeitig birgt die Infektion mit NG auch eine erhöhte Gefahr für eine Ansteckung mit anderen sexuell übertragbaren Infektionen (STI), wie zum Beispiel mit HIV oder Chlamydien [2,6].…”

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Die deutsche Laborlandschaft zu Diagnostik und Antibiotikaresistenztestung bei Neisseria gonorrhoeae

Loenenbach

Dudareva

Buder

et al. 2015

Bundesgesundheitsbl.

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The threat of untreatable gonorrhoea: implications and consequences for reproductive and sexual morbidity

Cited by 35 publications

References 29 publications

Assembly of NADPH Oxidase in Human Neutrophils Is Modulated by the Opacity-Associated Protein Expression State of Neisseria gonorrhoeae

Assembly of NADPH Oxidase in Human Neutrophils Is Modulated by the Opacity-Associated Protein Expression State of Neisseria gonorrhoeae

Azithromycin Resistance and Its Mechanism in Neisseria gonorrhoeae Strains in Hyogo, Japan

Die deutsche Laborlandschaft zu Diagnostik und Antibiotikaresistenztestung bei Neisseria gonorrhoeae

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