Associate Professor
Dept. of Oral Immunology and Infectious Diseases
Room 341, School of Dentistry
Office Phone: 502-852-8304
Email: matthew.ramsey@louisville.edu
ORCID ID: 0000-0001-7158-5120

Research Summary

Research in the M. Ramsey lab studies interactions between oral bacterial species with a focus on healthy commensals. We live in exciting time in Microbiology with massive observational datasets characterizing the species present in humans in each body site and in health vs disease. Currently, while we know a lot about what bacteria are present, there is very little investigation into what healthy microbes are doing, and whom they interact with. We believe that understanding these interactions will reveal ways in which we can maintain healthy communities, in order to prevent or reverse dysbiotic shifts that often occur in multiple oral diseases. Our current focus is on the highly abundant oral health associated microbes Haemophilus parainfluenzae and Corynebacterium matruchotii and their interactions with spatially adjacent bacterial species in oral biofilms. We utilize microbiome, imaging and transcriptome based technologies alongside bacterial genetics to understand the major drivers of community stability / composition in healthy hosts.

Current Projects

Mechanisms underlying spatial relationships in the human oral microbiome

The human microbiome project (HMP) provided an extensive dataset describing the composition of the microbiome in multiple body sites. Armed with this data we identified significantly positive correlations within sequence data to focus on several highly abundant and prevalent commensal microbes that are also underrepresented in disease conditions. Further, we then showed that spatial correlations between these species were present via species-specific fluorescent probe microscopy of human supragingival plaque (SUPP) samples. We selected two prominent candidate commensals, Haemophilus parainfluenzae and Corynebacterium matruchotii, and investigate their respective interactions with spatially adjacent Streptococcus species.

Using a reductionist approach, we compared in vitro mono vs cocultures of either H. parainfluenzae or C. matruchotii in coculture with Streptococcus mitis or S. cristatus. These data suggested multiple mechanisms of interaction between these species including competition and cooperation for certain salivary nutrients, stress responses and genes that are potentially involved in influencing host immune responses. We have shown that these communities both allow for crossfeeding of adjacent microbes on streptococcal-produced lactic acid as well as differences in vitamin synthesis and uptake in both species which suggest cooperative relationships. Further comparison of our in vitro transcriptomes to in vivo metatranscriptome data has revealed conserved changes in gene expression in each organism that are also present in in vitro coculture, suggesting that these interactions may influence each other the same way in the lab as well as in the host.

We are currently trying to identify further mechanisms of interaction between these species and others that we observe to reproducibly be in close proximity to them. We are also evaluating the fitness of gene knockouts for each species in pathways hypothesized to be important in both in vitro and in vivo interaction and quantifying their impact on fitness for each species. These data will indicate areas in which coculture associations may make a healthy plaque community more resilient or provide a prebiotic or nutrient which can be provided to the host to ensure that community structure is maintained in the onset of disease.

The influence of the healthy oral microbiome on host immune signaling

Based on our spatial relationship studies and transcriptome data discussed above, we identified several candidate genes in H. parainfluenzae and S. mitis, differentially expressed in coculture, that appear to have some relevance to host immune signaling and responses. We are currently investigating host neutrophil responses to each species in mono or coculture and have recently discovered that multiple pro-inflammatory cytokines are upregulated by neutrophils in response to these microbes in monoculture but are significantly diminished in coculture. Further we have determined that H. parainfluenzae renders S. mitis resistant to neutrophil-dependent killing in coculture. We are currently investigating which genes are responsible for these changes in either species. Once the involved genes are known, we hope to engineer strains of each bacteria that may individually be able to help modulate pro-inflammatory cytokine expression, as a potential candidate therapeutic for limiting inflammation during the onset of oral disease. These approaches as well as a general understanding of how these healthy microbe interactions help preserve healthy immune system responses are anticipated to have broad relevance  to understanding oral disease prevention and resolution.

Educational Background

• PhD - University of Texas, 2011
• MS - University of Oklahoma, 2003
• BS - Louisiana Tech University, 2000

Current Funding

Mechanisms underlying spatial interaction in the oral microbiota, National Institute of Dental and Craniofacial Research, R01DE027958 (PI)

Related Publications

de Palma TH, Powers C, McPartland MJ, Mark Welch J, Ramsey M. Essential genes for Haemophilus parainfluenzae survival and biofilm growth. mSystems. 2024 Sep 17;9(9):e0067424. doi: 10.1128/msystems.00674-24. Epub 2024 Aug 21. PubMed PMID: 39166876

Labossiere A, Ramsey M, Merritt J, Kreth J. Molecular commensalism-how to investigate underappreciated health-associated polymicrobial communities. mBio. 2023 Oct 31;14(5):e0134223. doi: 10.1128/mbio.01342-23. Epub 2023 Sep 27. Review. PubMed PMID: 37754569

Almeida E, Puri S, Labossiere A, Elangovan S, Kim J, Ramsey M. Bacterial multispecies interaction mechanisms dictate biogeographic arrangement between the oral commensals Corynebacterium matruchotii and Streptococcus mitis. mSystems. 2023 Oct 26;8(5):e0011523. doi: 10.1128/msystems.00115-23. Epub 2023 Aug 23. PubMed PMID: 37610230

de Palma TH, Loomis E, Perera D, Ramsey M. Whole-genome sequence of Haemophilus parainfluenzae EL1 isolated from healthy supragingival plaque. Microbiol Resour Announc. 2023 Oct 19;12(10):e0047623. doi: 10.1128/MRA.00476-23. Epub 2023 Sep 29. PubMed PMID: 37772865

Puri SR, Almeida E, Elangovan S, Labossiere A, Collins C, Ramsey M, Kim J. Mechanistic Assessment of Metabolic Interaction between Single Oral Commensal Cells by Scanning Electrochemical Microscopy. Anal Chem. 2023 Jun 6;95(22):8711-8719. doi: 10.1021/acs.analchem.3c01498. Epub 2023 May 25. PubMed PMID: 37228117

Perera D, McLean A, Morillo-López V, Cloutier-Leblanc K, Almeida E, Cabana K, Mark Welch J, Ramsey M. Mechanisms underlying interactions between two abundant oral commensal bacteria. ISME J. 2022 Apr;16(4):948-957. doi: 10.1038/s41396-021-01141-3. Epub 2021 Nov 3. PubMed PMID: 34732850

 Complete List of Published Work in MyBibliography

Affiliations

International Association for Dental Research (IADR)

American Association for Dental, Oral, and Craniofacial Research (AADOCR)

American Society of Microbiology (ASM)

NIDCR DSR Study Section, standing member

Associate Editor, Journal of Oral Microbiology