Boston College biologist Tim van Opijnen and computer scientist José Bento reveal how different strains of bacteria use different groups of genes to resist antibiotics. Their approach maps, ranks, and identifies where antibiotic sensitivity functions reside in the genome of strains of S. pneumoniae.
Tim van Opijnen (Boston College Assistant Professor of Biology), José Bento (Assistant Professor of Computer Science) and their colleagues received a $10 million grant from U.S. National Institutes of Health. Scientists undertook a “genome-wide” study to determine where drugs produce stress in the S. pneumoniae genome. They used transposon sequencing, or Tn-Seq, a technique developed by van Opijnen that quickly combs through millions of genetic sequences and singles-out gene functions in bacteria.
S. pneumoniae causes diseases that each year kill millions of people around the world, particularly the young and old. While antibiotics remain a crucial treatment option, the emergence of antibiotic-resistant strains of streptococcus leaves millions more people vulnerable to potentially lethal infection.
Using a novel gene sequencing technique, researchers at Boston College found that two strains of the same bacteria combat a common antibiotic with mostly different sets of genes and their underlying genetic networks, pointing to the need to develop antibiotic-sensitivity profiles for different bacterial species and the strains within them.
More than half of the sensitivity-profile genes that inhibited one strain’s sensitivity to the antibiotic had no effect in the other strain, the team reported. In addition, the project used analytical tools to untangle the underlying genomic networks to reveal further differences between the two strains in genetic-interactions and transcriptional regulation of genetic activity. Furthermore, the study confirmed that developing the antibiotic-sensitivity profile effectively shed new light on the influence of genetic background on the emergence of drug resistance, as well as on how bacteria react to the environmental stressors that influence how they evolve.
Through these detailed, multi-layered understandings of each bacterial strain, the researchers reported this opens a new route to identify strain-specific vulnerabilities in antibiotic-resisting genes. That could pave the way for the development of new or improved drugs or drug combinations capable of attacking infections now shielded by drug resistance.