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Genome-scale approaches to strengthen Neisseria gonorrhoeae epidemiological and antimicrobial resistance surveillance

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Resumo:Neisseria gonorrhoeae is the human pathogen responsible for the sexually transmitted disease gonorrhoea, whose burden remains a major public health concern. This bacterium has shown an extraordinary ability to develop antimicrobial resistance (AMR) to multiple classes of antimicrobials, with the advent of reaching a “superbug” status. With no available vaccine, managing gonorrhoea infections demands effective preventive measures, antibiotic treatments and epidemiological surveillance. National and international surveillance programmes are increasingly promoting the application of whole-genome sequencing (WGS) data to track N. gonorrhoeae circulation and the emergence and spread of AMR. The major goal of the PhD dissertation was to strengthen N. gonorrhoeae epidemiological and AMR surveillance using WGS. Particularly, we disclose the major AMR trends observed in Portugal throughout 16 years, by reporting data from the National Laboratory Network for Neisseria gonorrhoeae Collection (PTGonoNet), hosted at the Portuguese National Institute of Health (NIH). Using WGS data from across Europe, we report a comprehensive WGS-based genogroup assignment for N. gonorrhoeae. These genogroups represent main circulating lineages and were correlated with other typing techniques and linked to specific AMR signatures. Using a dynamic gene-by-gene approach, we performed the first genome-scale study of N. gonorrhoeae in Portugal, highlighting the genetic diversity of circulating strains, as well as potential transmission chains, which is essential to support epidemiological investigation. Finally, we evaluated a culture-independent strategy to obtain WGS data directly from clinical samples and its suitability for epidemiological surveillance and AMR detection. The findings presented in this dissertation constituted a turning point to consolidate the genomic epidemiology of gonococci in Portugal through the implementation of a WGS-based surveillance methodology in the Portuguese NIH. Ultimately, this work enhances N. gonorrhoeae surveillance by promoting the prospective monitoring of genogroup frequency and geographic spread, towards more oriented Public Health actions to control the spread of N. gonorrhoeae AMR.
Autores principais:Pinto, Miguel Cascais Ferreira
Assunto:Neisseria gonorrhoeae Antimicrobial resistance Surveillance Whole-genome sequencing
Ano:2021
País:Portugal
Tipo de documento:tese de doutoramento
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL
Descrição
Resumo:Neisseria gonorrhoeae is the human pathogen responsible for the sexually transmitted disease gonorrhoea, whose burden remains a major public health concern. This bacterium has shown an extraordinary ability to develop antimicrobial resistance (AMR) to multiple classes of antimicrobials, with the advent of reaching a “superbug” status. With no available vaccine, managing gonorrhoea infections demands effective preventive measures, antibiotic treatments and epidemiological surveillance. National and international surveillance programmes are increasingly promoting the application of whole-genome sequencing (WGS) data to track N. gonorrhoeae circulation and the emergence and spread of AMR. The major goal of the PhD dissertation was to strengthen N. gonorrhoeae epidemiological and AMR surveillance using WGS. Particularly, we disclose the major AMR trends observed in Portugal throughout 16 years, by reporting data from the National Laboratory Network for Neisseria gonorrhoeae Collection (PTGonoNet), hosted at the Portuguese National Institute of Health (NIH). Using WGS data from across Europe, we report a comprehensive WGS-based genogroup assignment for N. gonorrhoeae. These genogroups represent main circulating lineages and were correlated with other typing techniques and linked to specific AMR signatures. Using a dynamic gene-by-gene approach, we performed the first genome-scale study of N. gonorrhoeae in Portugal, highlighting the genetic diversity of circulating strains, as well as potential transmission chains, which is essential to support epidemiological investigation. Finally, we evaluated a culture-independent strategy to obtain WGS data directly from clinical samples and its suitability for epidemiological surveillance and AMR detection. The findings presented in this dissertation constituted a turning point to consolidate the genomic epidemiology of gonococci in Portugal through the implementation of a WGS-based surveillance methodology in the Portuguese NIH. Ultimately, this work enhances N. gonorrhoeae surveillance by promoting the prospective monitoring of genogroup frequency and geographic spread, towards more oriented Public Health actions to control the spread of N. gonorrhoeae AMR.