Of the many types of bacteria in the oral cavity and throat, one species is especially worrying because it can colonize the lungs, ear or even the meninges and make us ill. Danish researchers are now closer to understanding why most oral bacteria are harmless and a few are not.
Hundreds of bacterial species inhabit your mouth and throat, living in peaceful coexistence with you as a host. They just reside there and do no harm. If anything, their presence may benefit you.
However, there are also oral and throat bacteria that can go astray and cause pneumonia, an ear infection or even meningitis. One species that frequently causes illness is pneumococci (Streptococcus pneumoniae).
Researchers have long wondered why some of the mitis group of streptococci that otherwise seem similar can make people ill and others do not. Danish researchers will now elucidate why this happens.
In a recently published study, the researchers mapped the metabolism of one species in the oral cavity to examine whether differences in metabolism may determine whether a species can make people ill.
“Surprisingly, although the bacteria are so similar, they differ in their ability to make people ill. We are also not sure why pneumococci especially cause illness. We previously examined virulence factors as the reason why some bacteria in the mitis group of streptococci cause disease whereas others do not, but we did not find a smoking gun, so now we are seeking to find the reason in differences in the metabolism of the bacteria,” explains a researcher behind the results, Christian Salgård Jensen, specialist physician and PhD student, Department of Clinical Microbiology, Region Zealand, Slagelse, Denmark.
The research has been published in Frontiers in Genetics.
Mapping the genome and metabolism of oral bacteria
Christian Salgård Jensen and colleagues whole-genome sequenced Streptococcus oralis to identify which of its genes influence its metabolism.
The genomes of the various oral bacteria are so similar that Christian Salgård Jensen suspects that they all share roughly the same genes and signalling pathways for metabolism.
The question is just how the different bacteria express different parts of the metabolism and whether they have small differences that can strongly affect their ability to make people ill.
After whole-genome sequencing, the researchers used advanced mathematical models to identify the biological pathways that translate genes into the actual metabolism of the bacteria.
“The first part of the study, which involved discovering whether differences in metabolism may be the reason why some bacteria can cause disease whereas others do not, was mapping the metabolism of one species, which can then be compared with the others to identify differences. That is what we have done now,” says Christian Salgård Jensen.
Comparing metabolism between bacteria
The researchers created a library of the metabolism of Streptococcus oralis and then compared this with experimental data from the researchers’ laboratory and other laboratories.
The experimental data that showed which types of sugar the bacteria need to grow and which amino acids are essential were almost identical to the predictions made by the library.
The comparison with other bacteria means that the researchers can now see what each specific species needs to thrive and which types of sugar and amino acids the individual bacteria need.
“We created and validated the library for Streptococcus oralis, and now we are starting to do the same for pneumococci. We are sequencing a lot of strains; the next step is experiments that show what each one needs to grow, and then we can use our model to compare them,” explains Christian Salgård Jensen.
May lead to new types of antibiotics
Christian Salgård Jensen says that this is basic research, but finding significant differences in the metabolism between harmless and pathogenic bacteria can provide great perspectives in the long term.
For example, the researchers could discover that the pathogenic bacteria have some specific metabolic requirements resulting from specific genes that can be precisely targeted with medicine.
“In the longer term, our discoveries can lead to better treatments for people who harbour some types of pathogenic bacteria. Few new antibiotics have emerged recently, but this could be a way of finding some new ones,” says Christian Salgård Jensen.
“Reconstruction and validation of a genome-scale metabolic model of Streptococcus oralis (iCJ415), a human commensal and opportunistic pathogen” has been published in Frontiers in Genetics. Co-author Bernhard O. Palsson is the CEO of the Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.