High throughput sequencing of Antimicrobial Resistance: A One Health Approach

Summary

Antimicrobial resistance (AMR) is one of the greatest challenges facing both clinical (human) and veterinary medicine. The problem is exacerbated by the slow pace of development of new antimicrobial drugs. In developing countries, the causes of antimicrobial resistance are complex and may be attributed to different factors such as improper prescription practices and patient education, limited diagnostic facilities and the unauthorized prescription of antimicrobials in clinical settings and for non-human use such as in animal production. Therefore, tackling ongoing and emerging infectious disease epidemics and antimicrobial resistance require a synergistic collaboration to achieve common public health goals. “One Health” is a coordinated and holistic approach to meeting this demand which accounts for comprehensive comparisons across different human, animal and environmental reservoirs of disease.

The AMR challenge

Overuse and misuse of antibiotics in clinical and veterinary medicine contributes directly to the emergence of multidrug resistant (MDR) pathogens known as “superbugs”. In developing countries, this is driven in part by the broader weakness of antibiotic stewardship (ASP), as evidenced by the very limited, if any, regulations to govern the use of antibiotics in both humans and animals. Most developing countries report an alarming escalation in MDR infections, which have a major impact not only within each country but also on neighbouring nations, since dissemination of resistant strains can occur via both human travel and trade exchange, leading to the spread of MDR infections in hospitals, communities and in livestock herds. Most antimicrobial agents used in human medicine have analogues for veterinary practice, in which some powerful antibiotics are used as growth promotors and as empiric first-line agents in the treatment of mild or self-limiting infections. Overconsumption of these drugs leads to strong selective pressure in favour of MDR bacteria.

AMR is a significant barrier to achieving the Sustainable Development Goals (SDGs). For instance, SDG3 calls for ensuring healthy lives and promoting well-being for all at all ages, but overconsumption of antibiotics directly frustrates the goal of reducing the frequency of bloodstream infections due to MDR pathogens that are resistant to third generation cephalosporins (broad-spectrum antimicrobial agents useful in a variety of clinical situations.) Similarly, MDR pathogens undermine SDG2 (Zero hunger) and SDG8 (Decent work and economic growth) by undermining sustainable food production and food security.

Towards genomics-based AMR surveillance

Our laboratory studies microbial genomics to compare MDR pathogens to determine the complex dynamics of AMR profile, multi-host ecology, host adaptation and dissemination dynamics of various MDR, locally and globally. Through whole genome sequencing and the application of bioinformatics tools, our laboratory has identified different resistance determinants and mechanisms that advance the development of an AMR genomics-based surveillance program to inform decision makers on the application of targeted prevention and infection control policies and procedures for different clinical and veterinary sectors. Through comparative genomic analysis of multiple MDR pathogens at the human, food, environment and animal interface, our multidisciplinary research projects seeks to:

1. Characterize the genetic determinants and detect the complex dynamics of selection and transmission of AMR through a multidisciplinary One Health approach. High throughput sequencing is a more precise approach to quantifying the genomic relatedness of human and animal isolates, crucial to comprehensively strengthening AMR surveillance across species and environments;
2. Develop an open-access resource for comparative genomics (genomic databases and analysis pipelines), AMR phenotypic profiles, AMR outbreaks and emerging resistance of screened pathogens at the human, animal and environment interface. This resource will host and link genomic sequencing data and phenotypic antimicrobial susceptibility testing from different clinical, human, animal and environmental sources from different public and private online repositories and databases, thus facilitating the monitoring of AMR pathogens. Information will include various types of antimicrobial genes and resistant clones circulating in the region, and their mode of their dissemination across different hosts. This will enable all scientists to contribute to and work with each other’s data, the most way to advance discovery and treatment.

Future directions and applications

Implementation of different accessible bioinformatics tools available to forecast AMR determinants and mechanisms will further support pathogen surveillance and AMR tracking based on genomics. This will enable treatment of individual patients using “precision medicine” that is tailored to the characteristics of the particular pathogen and host. The data from these multidisciplinary projects will underpin an evidence-led strategic recommendation to enable local public health workers, researchers, community leaders, government officials and policy makers to focus resources on well-planned antibiotic stewardship programmes and provide feasible interventions to reduce the burden of MDR infections.

About Mohamed Elhadidy

Mohamed Elhadidy is an Egyptian Microbiologist and a professor of Biomedical Sciences at Zewail City of Science and Technology in Egypt. His research interests are in population genetics, and comparative genomic studies of bacterial pathogens and investigating the ecology, epidemiology and evolution of zoonotic bacterial pathogens causing human infection using different comparative genome analysis and population genetics studies. Elhadidy is a member of the African Academy of Sciences (AAS) Affiliate Programme, which recognises, mentors and develops early career researchers into world-class research leaders. He is also a member of the Global Young Academy and the Egyptian Young Academy of Sciences (EYAS), and National Microbiology Council.