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Interspecies Interactions in the Oral Microbiome: Modulating an Invasion-Resistance Mechanism

  • Author(s): Ferrer, Daniel
  • Advisor(s): Bradley, Peter;
  • Shi, Wenyuan
  • et al.

Interest in the various microbiomes of the human body is rising as more and more people recognize the importance of these communities in health and disease. They engage in several functions that benefit the host such as breakdown of non-digestible compounds into usable metabolites and protection against pathogenic microbes. The composition and stability of these communities is of the utmost importance as disruption of their stability is what leads to dysbiosis and illness. However, we still do not have a complete picture of how these communities protect themselves from alien microbes despite constant exposure to them. Take the oral cavity for example. The oral cavity is known to have over 700 different bacterial species living in it and has very little overlap with the population of the gut microbiome even though everything that persists in the gut must pass through the oral cavity. We know the environment plays a role in preventing exogenous species from establishing themselves, but we do not know what part the bacterial community itself plays. I set out to elucidate the answers to the question: How does the oral microbiome prevent foreign bacteria from establishing themselves and persisting in the oral cavity. My thesis explores the role of two bacteria, S. infantis and S. sanguinis, in an invasion resistance phenomenon using regulated H2O2 production to prevent foreign species from establishing themselves in the oral cavity.

There are two major components to my thesis: 1) the physiological characterization of the inhibitory relationship between S. infantis and S. sanguinis 2) the mechanistic characterization of the inhibitory relationship between S. infantis and S. sanguinis. To address the first component, I investigated how the interaction between S. infantis and S. sanguinis results in the observed reduction in H2O2 production. I determined that this reduction is neither due to the killing of S. sanguinis by S. infantis nor the degradation of H2O2 by S. infantis in liquid culture. The loss of H2O2 production appears to be due to a transcriptional inhibition of the H2O2 producing gene in S. sanguinis, spxB.

The second component of my thesis addresses how this inhibition of spxB transcription occurs. Live cells of S. infantis are required for inhibition of H2O2 production, however the supernatant from S. infantis cultures can inhibit H2O2 production, suggesting a contact-independent mechanism. The diffusible compound that inhibits H2O2 production is heat stable and not a result of a deficiency of an upstream component, pyruvate. While investigating this phenomenon on solid agar instead of liquid media, I determined that S. infantis secretes a diffusible compound that degrades H2O2 but is not pyruvate which is how this is accomplished in other spxB+ Streptococci. Finally, I began identifying genes in S. sanguinis potentially involved in regulating H2O2 production via a screen of an S. sanguinis mutant library.

My work provides insight into how the human microbiomes may maintain their stable composition and protect themselves from invasion. This will move the study of the role of the microbiome in human health and disease forward by illuminating more of the roles the bacterial themselves play. My work also makes contributions to the field of synthetic ecology. Interest has been growing in pre- and probiotics and how we might be able to manipulate the various human microbiomes to enhance human health or prevent disease. The more we know about how the microbiomes protect themselves and how they help their human hosts, the more capable we will be to engineer a better community or manipulate the community to enhance beneficial functions.

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