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Principal Investigator: Katherine Paige Lemon
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $400,000
Funding agency: National Institute of General Medical Sciences
The objective unifying our two areas of NIGMS-funded research is to identify molecular mechanisms underlying
microbe-microbe and microbe-host interactions involving D. pigrum and nasal Corynebacterium species that
shape the human nasal microbiota. Evidence indicates that Corynebacterium species and Dolosigranulum
pigrum play key roles in structuring a nasal microbiota beneficial to human health. For example, people with high
levels of Corynebacterium and/or D. pigrum in their nasal microbiota are less likely to be colonized by pathobionts
and, therefore, are at lower risk of invasive infections in other parts of their bodies. Similarly, nasal microbiota
dominated by Corynebacterium/D. pigrum are often associated with health rather than with diseases such as
otitis media and pneumonia. Our overarching hypothesis is that interactions between D. pigrum and
Corynebacterium species drive a beneficial health-promoting human nasal microbiota. A central goal of this
research is to shift from correlations in compositional data to causation by identifying molecular mechanisms that
underlie both in vivo associations and in vitro phenotypes. Our NIGMS-supported preliminary data show that
there are four common species of nasal Corynebacterium. Three of these are positively correlated with D. pigrum
and enhance D. pigrum growth in vitro. Furthermore, cocultivation of D. pigrum with Corynebacterium
pseudodiphtheriticum together robustly inhibits S. pneumoniae in vitro, compared to either alone. D. pigrum also
inhibits S. aureus growth in vitro. These in vitro results support a role for in vivo interactions with potential health
benefits. To understand microbe-microbe and microbe-epithelium interactions in the human nasal passages, we
will use human nasal epithelial organoids at an air-liquid interface (aka nasanoids) as an innovative biomimetic
model system in collaboration with our Organoid Core. Microbial communities are characterized by a network of
metabolic interactions among microbes and with the environment. Genomic analysis uncovered D. pigrum
auxotrophies indicating it depends on the host or microbial neighbors for key nutrients. Our research will address
gaps in understanding the food web that supports human nasal microbiota; the effects on the epithelium of
hosting microbes; and the physiology and function of potentially beneficial nasal bacteria. A key advantage of
using human nasal microbiota to identify metabolic interactions is that it is a self-contained bacterial-epithelial
system with regard to nutrients. We will use complementary approaches including pan-genomics, metabolic
modeling, dual bacteria-epithelium transcriptomics, metabolomics and genetic engineering. We will also tackle
key technical challenges in the nasal microbiome field to facilitate identification of metabolites, proteins and
genes involved in interactions. To advance research on D. pigrum and nasal Corynebacterium, we have
established a large culture collection of nasal bacteria from > 400 volunteers of all ages. By identifying metabolic
interactions between nasal Corynebacterium species, D. pigrum, and the nasal epithelium that sculpt a health-
promoting human nasal microbiota, we hope to catalyze new approaches for preventing infection.
Terms: <Affect><Age><Air><Area><Bacteria><Benign><Biochemical Pathway><Biologic Models><Biological Mimetics><Biological Models><Biomimetics><Causality><Cell Line><CellLine><Co-culture><Cocultivation><Coculture><Coculture Techniques><Collaborations><Collection><Communities><Corynebacterium><D pneumoniae><D. pneumoniae><Data><Diplococcus pneumoniae><Disease><Disorder><Environment><Epithelium><Etiology><Food Webs><Funding><Generalized Growth><Genes><Genetic Engineering><Genetic Engineering Biotechnology><Genetic Engineering Molecular Biology><Genomics><Goals><Growth><Health><Health Benefit><Health Promotion><Human><In Vitro><Infection><Infection prevention><Liquid substance><Metabolic><Metabolic Networks><Microbe><Model System><Modeling><Modern Man><Molecular><NIGMS><Nasal><Nasal Epithelium><Nasal Passages Nose><National Institute of General Medical Sciences><Nose><Nutrient><Organoids><Otitis Media><Persons><Phenotype><Physiology><Play><Pneumococcus><Pneumonia><Prevent infection><Proteins><Recombinant DNA Technology><Research><Respiratory System, Nose, Nasal Passages><Risk><Role><S aureus><S pneumoniae><S. aureus><S. pneumoniae><Salutogenesis><Shapes><Staph aureus><Staphylococcus aureus><Strains Cell Lines><Streptococcus pneumoniae><Structure><Surface><System><Tissue Growth><ages><auxotrophy><causation><community microbes><cultured cell line><disease causation><fluid><genetically engineered><host microbe association><host microbe relationship><host-microbe interactions><host-microbial interactions><host-microorganism interactions><in vivo><innovate><innovation><innovative><liquid><metabolism measurement><metabolomics><metabonomics><microbial><microbial community><middle ear infection><nasal microbial community><nasal microbiome><nasal microbiota><new approaches><novel approaches><novel strategies><novel strategy><ontogeny><pathobiont><polymicrobial community><promoting health><sinonasal microbiome><sinonasal microbiota><social role><transcriptomics><volunteer>