– If this germ becomes truly resistant to these antibiotics, it would have a very serious impact on millions of children around the world. That is a very concerning but plausible notion based on our findings. Development of resistance to beta-lactam antibiotics would have a major public health impact globally, said James M. Musser, M.D., Ph.D., lead author of the study and chair of the Department of Pathology and Genomic Medicine at Houston Methodist Hospital.

Musser and members of his department collaborated with nearly a dozen institutions across seven countries, and this research appears online in the Jan. 29 issue of the Journal of Clinical Microbiology.

Research published earlier in 2019 describing two related bacterial strains compelled Musser’s group at Houston Methodist Research Institute and his collaborators to undertake this sizeable international project. They exploited their genome sequence library derived from 7,025 group A streptococcus strains collected over several decades from countries around the world.

– Of these, we discovered approximately 2 % with gene mutations of interest. We then tested the strains in the clinical microbiology laboratory to confirm their decreased susceptibility to beta-lactam antibiotics, says Professor of Bacteriology Jaana Vuopio, one of the scientists who participated in the research.

Research highlights the importance of infectious disease follow-up

Nearly a third of the bacterial strains selected for the study were from Finland. The Finnish data was collected from the national population-based follow-up register of infectious diseases, which is based on an extensive national collaboration with clinical microbiology laboratories.

The research showed that over the years A streptococcus strains have tried to develop resistance to penicillin and other related antibiotics several times. This has happened at different points of time and in a number countries.

– We can no longer be lulled into believing that no A streptococcus strain will become resistant to these important and widely-used antibiotics. If these kinds of strains were to become common, treating even mild A streptococcus infections would be difficult, says Vuopio.

The findings also highlight how important it is to invest in diagnostics and the follow-up of infectious diseases so that these kinds of mutations can be identified as quickly as possible.

– The next steps for the investigative team involve experiments to understand how the mutations arise in human patients, how they may affect human disease, and how they may change the virulence of the germ, sums Chief Specialist Jari Jalava from the Finnish Institute for Health and Welfare.

Long thought to lack gene mutations that may lead to penicillin resistance, the findings of reduced susceptibility in some strains suggest that penicillin and related antibiotic treatments for strep throat may eventually become less effective or completely ineffective. These findings underscore the urgent need for a vaccine that protects humans against group A streptococcus.

– We could be looking at a worldwide public health infectious disease problem. When strep throat doesn’t respond to frontline antibiotics such as penicillin, physicians must start prescribing second-line therapies, which may not be as effective against this organism, said Musser, the Fondren Presidential Distinguished Chair at the Houston Methodist Research Institute and Houston Methodist Hospital.

Other researchers collaborating on this paper included Stephen B. Beres, Luchang Zhu and Randall J. Olsen (Houston Methodist Research Institute and Houston Methodist Hospital); Jaana Vuopio and Kirsi Gröndahl-Yli-Hannuksela (Institute of Biomedicine, University of Turku, Finland); Hanne-Leena Hyyryläinen (Finnish Institute for Health and Welfare, Helsinki, Finland); Karl G. Kristinsson (Landspitali University Hospital and University of Iceland, Reykjavik, Iceland); Jessica Darenberg (Public Health Agency of Sweden, Solna, Sweden); Birgitta Henriques-Normark (Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden); Steen Hoffmann (Statens Serum Institut, Copenhagen, Denmark); Dominque A. Caugant (Norwegian Institute of Public Health, Oslo, Norway); Andrew J. Smith and Diane S. J. Lindsay (Glasgow Dental Hospital, School University of Glasgow, Scottish Microbiology Reference Laboratory, Scotland); and David Boragine and Timothy Palzkill (Baylor College of Medicine).

The findings were published in the Journal of Clinical Microbiology.

More information:

Jaana Vuopio, Professor, Institute of Biomedicine, University of Turku, tel. +358 29 450 4547, jaana.vuopio@utu.fi

Jari Jalava, Chief Specialist, Finnish Institute of Health and Welfare, tel. +358 29 524 6629, jari.jalava@thl.fi