Kevin Mason, Ph.D.

Kevin Mason, Ph.D., is an Assistant Professor of Pediatrics at The Ohio State University School of Medicine in the Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital. Dr. Mason’s research program focuses on mechanisms of pathogenesis of nontypeable Haemophilus influenzae (NTHI), the causative bacterium of childhood otitis media and upper and lower respiratory tract diseases in both children and adults. Dr. Mason investigates the function of a critical uptake transporter that mediates bacterial nutritional status and resistance to host antimicrobial peptides, effectors of innate immunity.

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Gender:

• Male

Languages Spoken:

• English

Research Center:

• Center for Microbial Pathogenesis

Areas of Interest:

• 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 expresses 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. Lab Web Site: http://www.NationwideChildrens.org/Mason-Lab

Undergraduate School

• The Ohio State University
  Date Completed: 06/30/1992

Post Doctoral

• Wright State University
  Date Completed: 06/30/1998

2008–present

• Assistant Professor of Pediatrics, The Ohio State University

• Harrison A., Santana E.A., Szelestey B.F., Newsom D.E., White P. and Mason K.M. 2013. Ferric uptake regulator and its role in the pathogenesis of nontypeable Haemophilus influenzae.  Infection and Immunity. Vol. 81, no. 4. (April): 1221-1233.
• Raffel F.K., Szelestey B.R., Beatty W.L. and Mason K.M. 2013. The Haemophilus influenzae Sap transporter medites bacterium-epithelial cell homeostasis.  Infection and Immunity. Vol. 81, no. 1. (January): 43-54.
• Vogel,Andrew,R; Szelestey,Blake,R; Raffel,Forrest,K; Sharpe,Samantha,W; Gearinger,Rachel,L; Justice,Sheryl,S; Mason,Kevin,M. 2012. SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus.  Frontiers in cellular and infection microbiology. Vol. 2, no. January: e42.
• Shelton, C.L., Raffel, F.K., Beatty, W.L., Johnson, S.M., and. 2011. Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.  PLoS Pathogens. Vol. 7, no. 11. (November): eE1002360.
• Sharpe, S.W., Kuehn, M.J. and Mason, K.M. 2011. Elicitation of epithelial-derived immune effectors by outer membrane vesicles of nontypeable Haemophilus influenzae.  Infection and Immunity. Vol. 79, no. August: 4361-4369.
• Mason, K.M., Raffel, F.K., Ray, C.W. and Bakaletz, L.O. 2011. Heme Utilization by nontypeable Haemophilus influenzae is essential and dependent on Sap transporter function.  Journal of Bacteriology. Vol. 193, no. 10. (January): 2527-2535.
• McGillivary G., Mason K.M., Jurcisek J.A., Peeples M.E., Bakaletz L.O. 2009. Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae.  Cellular Microbiology. Vol. 11, no. 9. (September): 1399-1408.
• 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. Vol. 2, no. 75. (January): 958-965.
• Mason K.M., Bruggeman M.E., Munson R.S., Bakaletz L.O. 2006. The non-typeable Haemophilus influenzae Sap transporter provides a mechanism of antimicrobial peptide resistance and SapD-dependent potassium acquisition.  Molecular Microbiology. Vol. 62, no. 5. (December): 1357-1372.
• Mason K.M.; Munson R.S. Jr; Bakaletz L.O. 2005. A mutation in the sap operon attenuates survival of nontypeable Haemophilus influenzae in a chinchilla model of otitis media.  Infection And Immunity. Vol. 73, no. 1. (January): e599.
• Novotny L.A., Mason K.M., Bakaletz L.O. 2005. Development of a chinchilla model to allow direct, continuous, biophotonic imaging of bioluminescent nontypeable Haemophilus influenzae during experimental otitis media.  Infection And Immunity. Vol. 73, no. 1. (January): e609.
• 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.  The EMBO Journal. Vol. 23, no. 23. (November): e4538.
• Mason K.M., Munson R.S. Jr, Bakaletz L.O. 2003. Nontypeable Haemophilus influenzae gene expression induced in vivo in a chinchilla model of otitis media.  Infection And Immunity. Vol. 71, no. 6. (June): e3454.
• Mason K.M., Dryden T.D., Bigley N.J., Fink P.S. 1998. Staphylococcal enterotoxin B primes cytokine secretion and lytic activity in response to native bacterial antigens.  Infection And Immunity. Vol. 66, no. 11. (November): e5082.
• Curiel R.E., Mason K.M., Dryden T.D., Maurer M.J., Bigley N.J. 1998. Cytokines produced early in picornavirus infection reflect resistance or susceptibility to disease.  Journal Of Interferon & Cytokine Research: The Official Journal Of The International Society For Interferon And Cytokine Research. Vol. 18, no. 8. (August): e587.
• Mason K.M., Bigley N.J., Fink P.S. 1998. Development of a novel in vitro co-culture system for studying host response to native bacterial antigens.  Journal Of Immunological Methods. Vol. 211, no. 1-2. (February): e147.
• A Harrison and KM Mason. Pathogenesis of Haemophilus influenzae in humans. In Emerging and Re-Emerging Human Infections. Edited by John Wiley & Sons/Wiley blackwell Press.