Genomic analysis of the meningococcal ST-4821 complex–Western clade, potential sexual transmission and predicted antibiotic susceptibility and vaccine coverage

Jay Lucidarme*, Bingqing Zhu, Li Xu, Xilian Bai, Yuan Gao, Juan José González-López, Robert Mulhall, Kevin J. Scott, Andrew Smith, Paola Stefanelli, Bianca Stenmark, Paul Torpiano, Georgina Tzanakaki, Raymond Borrow, Zhujun Shao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Introduction The ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates. Methods Genomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST. Results Four lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC <0.03 mg/L) and reduced penicillin susceptibility (MIC 0.094 to 1 mg/L). A third of these were from anogenital sites in men who have sex with men and had unique denitrification gene alleles. Generally 4CMenB vaccine strain coverage was reliant on strain-specific NHBA peptides. Discussion The previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape.

Original languageEnglish
Article numbere0243426
JournalPLoS ONE
Issue number12 December
Publication statusPublished - Dec 2020

Bibliographical note

Funding Information:
This work was supported by grants (ZS) from the National Key Program for Infectious Disease of China (contract no. 2013ZX10004221 and 2018ZX10714002-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This publication made use of the Neisseria Multi Locus Sequence Typing website (https:// sited at the University of Oxford [43]. The development of this site has been funded by the Wellcome Trust and European Union. The authors would like to thank Dr Desiree Bennett and Dr Robert Cunney of the Irish Meningitis and Sepsis Reference Laboratory, Children?s Health Ireland at Temple Street, Dublin, Ireland, and Dr. Judit Serra-Pladevall from the Clinical Microbiology Department of Hospital Universitari Vall d?Hebron. Thank you also to Dr David Pace?Department of Child and Adolescent Health, Mater Dei Hospital, Malta, and Ms Marlene Farrugia, Ms Sabrina Goodlip, Ms Julie Haider, Dr Graziella Zahra?Department of Pathology, Mater Dei Hospital, Malta for their instrumental contribution to the Maltese meningococcal carriage study referred to in this research. Thank you to Roisin Ure of the Bacterial Respiratory Infection Service, Scottish Microbiology Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom and Dr Andrew Winter, Consultant in Sexual Health & HIV Medicine & Joint Clinical Lead for e-Health, NHS Greater Glasgow and Clyde. Thank you to Dr Paola Vacca of the Department of Infectious Diseases, Istituto Superiore di Sanit?, Rome, Italy, and Andrea Ciammaruconi, Antonella Fortunato, Silvia Fillo, and Florigio Lista of the Scientific Department, Army Medical Center, Rome, Italy. We would also like to thank Aiswarya Lekshmi and the staff of the Public Health England Meningococcal Reference Unit.

Publisher Copyright:
© 2020 Lucidarme et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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