Neisseria gonorrhoeae host adaptation and pathogenesis

Quillin, Sarah J.; Seifert, H. Steven

doi:10.1038/nrmicro.2017.169

Cited by 256 publications

(257 citation statements)

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“…The oropharynx represents a pivotal site for N. gonorrhoeae residency [5]: it is a suitable ecological niche for NG to replicate and persist over time [6]. Moreover, commensal Neisseria species found in this site act as a significant reservoir for genetic material, conferring cephalosporin resistance in N. gonorrhoeae, and, thus, potentially, leading to the emergence of multidrug resistant gonorrhoea [7,8].…”

Section: Introductionmentioning

confidence: 99%

Pharyngeal microbiome alterations during Neisseria gonorrhoeae infection

et al. 2020

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Pharyngeal gonorrhoea is a common sexually transmitted infection among 'men having sex with other men' (MSM). Neisseria gonorrhoeae (NG) pharyngeal infections are usually characterized by the absence of symptoms, acting as an important reservoir for their further spread. To the best of our knowledge, no information about the composition of the pharyngeal microbiome during an ongoing NG infection is currently available. Therefore, in this study, we characterized the pharyngeal bacterial community profiles associated with NG infection in a well-selected cohort of HIV-negative MSM reporting unsafe oral intercourse. A total of 70 pharyngeal swabs were considered, comparing non-infected subjects (n = 45) versus patients with pharyngeal gonorrhoea (n = 25) whose microbiota composition was analyzed from pharyngeal swabs through sequencing of hypervariable V3-V4 regions of the 16S rRNA gene. The pharyngeal microbiome of all subjects was dominated by Prevotellaceae, Veillonellaceae and Streptococcaceae families. Patients with pharyngeal gonorrhoea harboured a pharyngeal microbiome quite similar to negative subjects. Nevertheless, when looking to less-represented bacterial species (relative abundance approximately 1% or less), an imbalance between aerobe and anaerobe microorganisms was observed in NGinfected patients. In particular, the pharyngeal microbiome of NG-positive individuals was richer in several anaerobes (e.g. Treponema, Parvimonas, Peptococcus, Catonella, Filifactor) and poorer in various aerobe genera (i.e. Pseudomonas, Escherichia), compared to non-infected controls. No significant differences were noticed in the distribution of commensal Neisseria species of the oropharynx between NG-positive and negative subjects. Metabolic variations induced by changes in the microbiome abundance were assessed by a functional prediction of the bacterial metabolic pathways: a more abundant involvement of D-glutamine and D-glutamate metabolism, carbohydrate metabolism, as well as a greater activation of the energy metabolism was observed in patients with pharyngeal gonorrhoea compared to non-infected individuals. Information about the bacterial composition of the pharyngeal microbiome in case of gonorrhoea could shed light on the pathogenesis of the infection and open new perspectives for the prevention and control of this condition.

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Section: Introductionmentioning

confidence: 99%

Pharyngeal microbiome alterations during Neisseria gonorrhoeae infection

et al. 2020

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“…Antibiotics have played a key role in shaping gonococcal evolution 1–3 , with N. gonorrhoeae gaining resistance to each of the first line antibiotics used to treat it 4–6 . As N. gonorrhoeae is an obligate human pathogen, the mucosal niches it infects—most commonly including the urethra, cervix, pharynx, and rectum—must also influence its evolution 7 . The gonococcal phylogeny suggests the interaction of these factors, with an ancestral split between a relatively drug-susceptible lineage circulating primarily in heterosexuals and a relatively drug-resistant lineage circulating primarily in men who have sex with men 3 .…”

Section: Introductionmentioning

confidence: 99%

Increased antibiotic susceptibility inNeisseria gonorrhoeaethrough adaptation to the cervical environment

Mortimer

Hicks

et al. 2020

Preprint

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28Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and 29 antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that 30 have reverted to susceptibility regularly appear, prompting questions about which pressures 31 compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide 32 association on the largest collection of N. gonorrhoeae isolates to date (n=4882) to identify loss-33 of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased 34 antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical 35 isolates relative to urethral isolates (odds ratio (OR) = 3.74, 95% CI [1.98-6.70]). In support of a 36 model in which pump expression incurs a fitness cost in this niche, cervical isolates were also 37 enriched relative to urethral isolates in LOF mutations in the mtrCDE activator mtrA (OR = 8.60,) and in farA, a subunit of the FarAB efflux pump (OR = 6.25, 95% CI [3.90-39 9.83]). In total, approximately 1 in 3 cervical isolates (36.4%) contained a LOF mutation in either 40 the efflux pump components mtrC or farA or the activator mtrA. Our findings extend beyond N. 41 gonorrhoeae to other Neisseria: mtrC LOF mutations are rare (<1%) in the primarily 42 nasopharyngeal-colonizing N. meningitidis in a collection of 14,798 genomes but enriched in a 43 heterosexual urethritis-associated lineage (8.6%, p = 9.90×10 -5 ), indicating that efflux pump 44 downregulation contributes broadly to the adaptation of pathogenic Neisseria to the female 45 urogenital tract. Overall, our findings highlight the impact of integrating microbial population 46 genomics with host metadata and demonstrate how host environmental pressures can lead to 47 increased antibiotic susceptibility. 48 49 50 51Neisseria gonorrhoeae is the causative agent of the sexually transmitted disease gonorrhea. 52Antibiotics have played a key role in shaping gonococcal evolution 1-3 , with N. gonorrhoeae 53 gaining resistance to each of the first line antibiotics used to treat it 4-6 . As N. gonorrhoeae is an 54 obligate human pathogen, the mucosal niches it infects-most commonly including the urethra, 55 cervix, pharynx, and rectum-must also influence its evolution 7 . The gonococcal phylogeny 56 suggests the interaction of these factors, with an ancestral split between a relatively drug-57 susceptible lineage circulating primarily in heterosexuals and a relatively drug-resistant lineage 58 circulating primarily in men who have sex with men 3 . 59 60 Despite the deeply concerning increase in antibiotic resistance reported in gonococcal 61 populations globally 8 , some clinical isolates of N. gonorrhoeae have become more susceptible 62 to antibiotics 9,10 . This unexpected phenomenon prompts questions about which environmental 63 pressures could be drivers of increased susceptibility and the mechanisms by which 64 suppression or reversion of resistance may occur. To address these questions, we analy...

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“…Neisseria gonorrhoeae (Gc) is a strict human pathogen and the causative agent of the sexually transmitted infection, gonorrhea (Quillin and Seifert, ). Symptomatic Gc infection is characterized by a robust innate immune response consisting of an influx of polymorphonuclear leukocytes to the site of infection.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional initiation of a small RNA, not R‐loop stability, dictates the frequency of pilin antigenic variation in Neisseria gonorrhoeae

Prister

Ozer

Cahoon

et al. 2019

Molecular Microbiology

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Summary Neisseria gonorrhoeae, the sole causative agent of gonorrhea, constitutively undergoes diversification of the Type IV pilus. Gene conversion occurs between one of the several donor silent copies located in distinct loci and the recipient pilE gene, encoding the major pilin subunit of the pilus. A guanine quadruplex (G4) DNA structure and a cis‐acting sRNA (G4‐sRNA) are located upstream of the pilE gene and both are required for pilin antigenic variation (Av). We show that the reduced sRNA transcription lowers pilin Av frequencies. Extended transcriptional elongation is not required for Av, since limiting the transcript to 32 nt allows for normal Av frequencies. Using chromatin immunoprecipitation (ChIP) assays, we show that cellular G4s are less abundant when sRNA transcription is lower. In addition, using ChIP, we demonstrate that the G4‐sRNA forms a stable RNA:DNA hybrid (R‐loop) with its template strand. However, modulating R‐loop levels by controlling RNase HI expression does not alter G4 abundance quantified through ChIP. Since pilin Av frequencies were not altered when modulating R‐loop levels by controlling RNase HI expression, we conclude that transcription of the sRNA is necessary, but stable R‐loops are not required to promote pilin Av.

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Neisseria gonorrhoeae host adaptation and pathogenesis

Cited by 256 publications

References 177 publications

Pharyngeal microbiome alterations during Neisseria gonorrhoeae infection

Pharyngeal microbiome alterations during Neisseria gonorrhoeae infection

Increased antibiotic susceptibility inNeisseria gonorrhoeaethrough adaptation to the cervical environment

Transcriptional initiation of a small RNA, not R‐loop stability, dictates the frequency of pilin antigenic variation in Neisseria gonorrhoeae

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