Mason, Kevin

Background: 
Education:
1998 - Ph.D. Immunology, Wright State University, Dayton, Ohio
     
1992 - B.S. Microbiology, The Ohio State University, Columbus, Ohio

Professional:
2008-present: Assistant Professor of Pediatrics, The Ohio State University School of Medicine and The Research Institute at Nationwide Children’s Hospital, Center for Microbial Pathogenesis, Columbus, Ohio.

2006- 2008: Research Scientist, Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital (f.k.a. Columbus Children’s Research Institute), Columbus, Ohio.

2000- 2006: Postdoctoral Researcher (Mentor:  Dr. Lauren Bakaletz), Center for Microbial Pathogenesis, Columbus Children’s Research Institute, Columbus, Ohio.

1998-2000: Postdoctoral Researcher (Mentor:  Dr. Meta Kuehn), Dept. of Biochemistry, Duke University, Durham, North Carolina. 

Description of Research:
Studies in my laboratory focus on understanding the complex molecular mechanisms that underlie bacterial pathogenesis and the host response.  Nontypeable Haemophilus influenzae (NTHi) is a common member of the host normal flora (a commensal) and yet predominates in both chronic otitis media with effusion, acute otitis media and in other localized respiratory diseases such as acute sinusitis, community-acquired pneumonia and has important consequences in patients with chronic obstructive pulmonary disease and cystic fibrosis (opportunistic pathogen).  We hypothesized that NTHi differentially express a number of genes as the microbe transitions to an opportunistic disease state.  Our investigations provided one of the earliest description and understanding of Haemophilus pathogenesis in vivo.  Importantly, NTHI adaptation to the diverse host environment resulted in the up-regulation of sap (sensitivity to antimicrobial peptides) operon gene expression, previously shown in other microorganisms to mediate resistance to killing by antimicrobial peptides (APs), key components of the host innate immune response.  These genes encode the Sap transporter, a member of an ABC transporter family that mediates recognition of small peptides, cations, or iron-containing proteins, which are then targeted for transport across the inner membrane into the bacterial cytoplasm.  We hypothesized that the pathogenic potential of NTHI is dictated by its ability to resist immune-mediated clearance mechanisms and specifically, killing by host APs.  Using genetic tools and biophotonic imaging of NTHi-infected chinchillas, we demonstrated that the sap genes are expressed in vivo early in infection and mutants defective in sap gene expression are sensitive to killing by host APs, and thus, are rapidly cleared in vivo.  Our work showed that APs directly bind the Sap transporter binding protein, supporting a model of AP transport to the bacterial cytoplasm and subsequent proteolysis or destruction, and initiation of a regulatory cascade that activates other resistance determinants.  We further demonstrated that components of the Sap transporter are also required for potassium uptake in NTHi, a function which counters rapid potassium efflux from the bacterium, a hallmark of AP lethality.  Current work in my laboratory continues to define how NTHI senses and transports APs, and define a role for Sap proteins in ATP-dependence on potassium transport, thus supporting a dual molecular mechanism that promotes bacterial survival and establishment of disease.  Further, we are interested in the role Sap gene products play in NTHi survival on epithelial cells since mutations in the Sap transporter alter NTHi biofilm formation, adherence properties and alter host cell responses.  Since Sap system homologues are conserved among bacterial species, our long-range goal is to better define a global resistance mechanism which, if targeted, could have far-reaching implications and therapeutic value.

Selected Publications:
1. Mason, K.M., Munson, R.S., Bakaletz, L.O. (2003).  Gene expression induced in vivo in a chinchilla model of otitis media due to nontypeable Haemophilus influenzae (NTHi).  Infect Immun, 71(6):3454.

2. Kesty, N.C*., Mason, K.M*., Reedy, M., Miller, S.E., Kuehn, M.J.  (2004).  Enterotoxigenic Escherichia coli vesicles target toxin delivery into mammalian cells.  EMBO J, 23(23):4538.
*Equal contribution

3. Mason, K.M., Munson Jr., R.S., Bakaletz, L.O. (2005).  A mutation in the sap operon attenuates survival of NTHI in a chinchilla model of otitis media.  Infect Immun, 73(1):599.

4. Novotny LA, Mason, K.M., Bakaletz, L.O.) (2005). Development of a chinchilla model to allow direct continuous biophotonic imaging of bioluminescent NTHI during experimental otitis media. Infect Immun, 73(1):609.

5. Mason, K.M., Bruggeman, M.E., Munson Jr., R.S., Bakaletz, L.O.  (2006). The nontypeable Haemophilus influenzae Sap transporter provides a mechanism of antimicrobial peptide resistance and SapD-dependent potassium acquisition.  Mol Micro.  62(5):1357-1372.

6. Hong, W*., Mason, K.M.*, Jurcisek, J.A., Novotny, L.A., Bakaletz, L.O., Swords, W.E.  (2007).       Phosphorylcholine decreases early inflammation and promotes establishment of stable biofilm communities of NTHI strain 86-028NP in the chinchilla models of otitis media.  Infect Immun, 75(2):958-965.
*Equal contribution

Contact Info: 
The Research Institute at Nationwide Children's Hospital and
The Ohio State University School of Medicine
Center for Microbial Pathogenesis
700 Children's Drive, W531
Columbus, OH 43205
Phone:  614-355-3534
Fax:  614-722-2818
E-mail:  kevin.mason@nationwidechildrens.org

Links:
The Research Institute at Nationwide Children's Hospital
Dr Mason's Page at Nationwide Children's Hospital