First database of multidrug-resistant bacterial genomes created in Brazil

To contribute to the monitoring and control of multidrug-resistant bacteria, researchers at the University of São Paulo (USP) in Brazil and collaborators have created One Health Brazilian Resistance (OneBR), a platform and genomic database with epidemiological, phenotypic and genetic information on microorganisms classified by the World Health Organization (WHO) as a “critical priority”, against which new antibiotics are urgently needed because existing drugs are no longer effective.

Data on some 500 human pathogens is currently available on the platform, and the total will soon rise to 700. The initiative is supported by FAPESP, the National Council for Scientific and Technological Development (CNPq), and the Bill & Melinda Gates Foundation. 

“The platform isn’t confined to bacteria that infect humans. It also covers the veterinary field, meaning pathogens that cause infections in livestock and pets, as well as environmental and food microbiology. We based it on the One Health concept [recognizing the interconnection between human, plant and animal health and the environment they share],” Nilton Lincopan, a professor at the Biomedical Sciences Institute (ICB-USP) and coordinator of OneBR, told Agência FAPESP.

Another aim of the group is to include data collected by Latin American colleagues. “We’re talking to researchers in Chile, Argentina, Uruguay and Ecuador, among others. It would be more interesting to monitor bacteria at the continental level, given the significant circulation of people and animals between countries. The platform is like Lego. We build the base and from then on the possibilities are infinite,” Lincopan said.

Access to the material is free and online, with no need for registration or authorization. Users simply go to the site and navigate. The information available includes where the pathogen was isolated (with geolocation data for hospitals and health services), patient clinical data (isolation from skin or blood, for example; date isolated; diseases caused; medications administered; whether the patient was hospitalized, etc.); epidemiological data (number of cases reported and geographical distribution, for example); and whole-genome sequence, highlighting the main resistance and virulence genes. All this information can help physicians choose an effective antibiotic.

The genomes in the database were sequenced by Lincopan’s team. Bacterial isolates sent by collaborators throughout Brazil are stored in a biorepository hosted by USP.

“Suppose a multi-resistant bacterium is detected in a patient in Recife [the capital of Pernambuco, some 2,000 km from São Paulo]. A health worker searches in the database and finds that the same clone was isolated by a hospital in São Paulo the previous year. They can ask whether the patient was admitted to the hospital and, if so, alert the institution to the spread and possible origin of the pathogen,” Lincopan said.

The Big Data platform will be useful not just for medical and epidemiological surveillance teams, but also for vets, biologists, environmental engineers and researchers linked to biotechnology, Lincopan believes.

“For example, you can search for molecular markers that could be used to develop diagnostic kits. Another application we’re exploring with colleagues in the field of artificial intelligence [AI] is antibiogram automation based on genomic data,” he said.

An antibiogram is a test that shows how susceptible a bacterium is to a variety of antibiotics. Currently, the technique involves culturing microorganisms in the laboratory for about 48 hours. With genomic data and AI, a result could be reached on the same day as the diagnosis.

Global challenge

In 2017, WHO published its first-ever list of antibiotic-resistant “priority pathogenic agents”, specifying 12 families of bacteria that pose the greatest threat to human health. The list is intended to guide and promote research and development in new antibiotics as part of WHO’s efforts to address growing global resistance to antimicrobial medicines. 

The list is divided into the categories critical, high and medium priority according to the urgency of the need for new antibiotics. The most critical group comprises multidrug-resistant bacteria that pose a particular threat in hospitals, nursing homes, and patients whose care requires devices such as ventilators and blood catheters. They include Acinetobacter baumannii, Pseudomonas aeruginosa, and various Enterobacteriaceae (e.g. Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, and Proteus spp), all of which can cause severe and often deadly infections, and have become resistant to a large number of antibiotics, including carbapenems and third-generation cephalosporins, the best available antibiotics for treating multidrug-resistant bacteria.

The second and third tiers in the list – the high- and medium-priority categories – contain other increasingly drug-resistant bacteria that cause more common diseases such as gonorrhea and salmonella food poisoning. 

One of the first Brazilian studies to analyze genomic data available from the platform was led by Bruna Fuga, a postdoc at ICB-USP. The findings are published in Microbiology Spectrum, a journal of the American Society for Microbiology. The article warns of the rapid spread and adaptation of international E. coli strains, and of the convergence of a wide resistome (genes resistant to antimicrobials) and virulome (virulence genes) at the human-animal-environmental interface, which must be considered a One Health challenge for a post-pandemic scenario.

More information On OneBR and studies using the database published so far can be found at: onehealthbr.com. 

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.