An international team of researchers has for the first time analyzed in detail the evolution and spread of a special strain of methicillin-resistant Staphylococcus aureus (MRSA). The so-called „Bengal Bay“ clone combines a special virulence and the potential for worldwide spread with the multi-resistance of hospital germs. For the elaborate analysis, 38 scientists from 15 countries collaborated over 8 years. InfectoGnostics researchers from the Leibniz Institute for Photonic Technologies (Leibniz-IPHT) and Abbott (Alere Technologies) in Jena were instrumental in the analysis of the gene sequences. The results were recently published in the journal „mBio“ of the American Society for Microbiology (DOI: 10.1128/mBio.01105-19).

Originally, it was a fairly rare and little-known strain of MRSA that English infectiologists discovered about 15 years ago in patients who had traveled to the Bay of Bengal region. But further detections in different parts of the world and the special characteristics of the Bengal Bay clone caught the attention of more and more researchers: This bacterium appeared mostly outside of hospitals, but showed many antibiotic resistances that were really only known from typical hospital pathogens. In addition, it was being detected more and more frequently in other countries. At a congress in Lyon in the summer of 2012, a number of scientists from different countries therefore decided to collect isolates of this MRSA clone and analyze their genomes. Together, they set themselves the goal of understanding the evolution and spread routes of this particular strain.

For the study, 340 isolates of the Bengal Bay clone were collected in 14 countries and then analyzed using whole genome sequencing. Additional experimental data on biofilm formation, growth and toxicity were also collected. For this purpose, the Jena-based InfectoGnostics researchers from the group of Prof. Ralf Ehricht (Leibniz-IPHT) performed virtual microarray analyses on the data of the isolated strains, which significantly simplified evaluation and interpretation of the genome sequences. At the end of years of research, the results of all 38 scientists involved in the paper were pieced together like a puzzle to trace the phylogenetic evolution of the bacterium.

This now-completed analysis of the genomes of hundreds of representative isolates of the strain shows that even assertive, virulent MRSA strains outside the hospital incorporate numerous resistance genes into their genomes – behavior that is otherwise more typical of hospital germs. „We were able to show with the current analysis that precursors of the Bengal Bay clone have existed in India and Bangladesh since the 1960s. The bacterium has gradually integrated mobile genetic elements such as plasmids and gene cassettes into its own genome over the past 30 years, acquiring a whole range of resistance mechanisms. To date, no such multidrug-resistant strain is known that has been able to spread so widely outside hospitals and also carries so many virulence factors,“ explains Dr. Stefan Monecke of Leibniz-IPHT, who was involved in the microarray analyses in Jena.

Improved diagnostics and regulated antibiotic administration urgently needed

According to Dr. Monecke, such a strain poses a problem especially for resource-poor countries that bear the brunt of the outbreak: „Outside the clinic, MRSA strains were previously mostly displaced by more virulent, but more antibiotic-sensitive, competing strains. In contrast, our results show that bacteria circulating outside the hospital setting in the healthy population may well acquire a resistance profile comparable to hospital germs, without affecting their virulence and ability to spread.“ The emergence of such a bacterial strain, he said, has been fueled primarily by uncontrolled antibiotic administration and social factors, such as high population density with poor living conditions.

While a complete and comparative genomic analysis across more than a dozen countries would be very costly, Dr. Monecke added, „such international collaborations are imperative to truly understand a global problem such as antibiotic resistance and to take early preventive measures. Our results show: We need improved diagnostics as soon as possible – for example, inexpensive rapid tests to detect MRSA and its virulence factors – and stricter regulation of antibiotic use.“

In the image above:
Staphylococcus colonies on blood-containing culture medium (Photo: InfectoGnostics/Fotostudio Ebenbild).