Genomic Characterization of Emerging Bacterial Uropathogen Neisseria meningitidis, Which Was Misidentified as
Kimberley V Sukhum1,2, Sophonie Jean2,3, Meghan Wallace2
1The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Abstract:
Neisseria meningitidis and Neisseria gonorrhoeae are pathogenic bacteria that can cause human infections. While N. meningitidis infections are associated with bacterial meningitis and bacteremia, a strain of N. meningitidis, isolated from the urogenital system, has recently been associated with urethritis. As this strain is becoming prominent as an emerging pathogen, it is essential to assess identification tools for N. meningitidis and N. gonorrhoeae urogenital isolates. Consecutive N. meningitidis isolates recovered from urogenital cultures of symptomatic patients with presumptive diagnoses of gonorrhea and a random selection of N. gonorrhoeae isolates recovered from the same population within the same time frame were characterized with routine identification systems, antimicrobial susceptibility testing, and whole-genome sequencing. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), multilocus sequence typing, 16S rRNA gene sequence, and average nucleotide identity methods accurately identified 95% (18/19) of N. meningitidis and N. gonorrhoeae isolates. With the Aptima Combo 2 CT/NG test, 30% (3/10) of N. meningitidis isolates were misidentified as N. gonorrhoeae, but no misidentifications were found with the Xpert CT/NG nucleic acid amplification test (NAAT). Phylogenetic core genome and single nucleotide polymorphism (SNP)-based grouping analyses showed that urogenital N. meningitidis isolates were highly related and phylogenetically distinct from N. gonorrhoeae and respiratory N. meningitidis isolates but similar to urogenital N. meningitidis isolates from patients with urethritis in the United States. Urogenital N. meningitidis isolates were predominantly azithromycin resistant, while N. gonorrhoeae isolates were azithromycin susceptible. These data indicate that urogenital isolates of N. meningitidis can cause false-positive detections with N. gonorrhoeae diagnostic assays. Misidentification of urogenital N. meningitidis isolates may confound public health-related activities for gonorrhea, and future studies are needed to understand the impact on clinical outcome of N. meningitidis urogenital infection.
Insights
Certain Neisseria meningitidis strains cause urethritis, leading to misidentification as Neisseria gonorrhoeae by some diagnostic tests. This highlights the need for accurate identification of these emerging urogenital pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Genomics
Background:
- Neisseria meningitidis and Neisseria gonorrhoeae are pathogenic bacteria causing human infections.
- While N. meningitidis typically causes meningitis and bacteremia, a urogenital strain is emerging as a cause of urethritis.
- Accurate identification of these bacteria is crucial, especially with the rise of N. meningitidis in urogenital infections.
Purpose of the Study:
- To assess the accuracy of identification tools for N. meningitidis and N. gonorrhoeae in urogenital isolates.
- To evaluate the phylogenetic relationship and antimicrobial susceptibility of urogenital N. meningitidis.
- To determine the potential for misidentification of urogenital N. meningitidis as N. gonorrhoeae.
Main Methods:
- Characterization of consecutive N. meningitidis urogenital isolates and random N. gonorrhoeae isolates using routine identification systems.
- Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed.
- Identification methods included MALDI-TOF MS, multilocus sequence typing, 16S rRNA gene sequencing, average nucleotide identity, Aptima Combo 2 CT/NG, and Xpert CT/NG NAAT.
Main Results:
- MALDI-TOF MS, multilocus sequence typing, 16S rRNA gene sequencing, and average nucleotide identity accurately identified 95% of isolates.
- The Aptima Combo 2 CT/NG test misidentified 30% of N. meningitidis isolates as N. gonorrhoeae; the Xpert CT/NG NAAT showed no misidentifications.
- Phylogenetic analyses confirmed urogenital N. meningitidis isolates are distinct from N. gonorrhoeae and respiratory N. meningitidis.
- Urogenital N. meningitidis isolates were predominantly azithromycin resistant, unlike azithromycin-susceptible N. gonorrhoeae.
Conclusions:
- Urogenital N. meningitidis can be misidentified as N. gonorrhoeae by certain diagnostic assays, potentially impacting public health surveillance for gonorrhea.
- Accurate diagnostic tools are essential for distinguishing between these two Neisseria species in urogenital samples.
- Further research is needed to understand the clinical implications of urogenital N. meningitidis infections.
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