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.

View CV »

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

• 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

• 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. (August) http://iai.asm.org/cgi/content/abstract/IAI.05332-11v1?etoc. (IF: 4.205)
• 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. : 2527-2535. (IF: 3.94)
• 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 1): 1399-1408. (IF: 6.057)
• 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. : 958-965. (IF: 4.205)
• 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 1): 1357-1372. (IF: 5.361)
• 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 1): 609. (IF: 4.205)
• 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 1): 599. (IF: 4.205)
• 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 24): 4538. (IF: 8.993)
• Bowyer SM; Moran JE; Mason KM; Constantinou JE; Smith BJ; Barkley GL; Tepley N. 2004. MEG localization of language-specific cortex utilizing MR-FOCUSS.  Neurology. Vol. 62, no. 12. (June 22): 2247.
• 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 1): 3454. (IF: 4.205)
• 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 1): 5082. (IF: 4.205)
• 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 1): 587. (IF: 1.627)
• 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 1): 147. (IF: 2.347)
• Mason KM, Bigley NJ and Fink PS. 1996. Superantigen pretreatment alters host immuneresponse to oral microflora [Abstract]. FASEB J.. 10 ed. no. 1043: A1180. [Peer Reviewed] (Published)
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2007. The Sap transporter is critical for the commensal and pathogenic behavior of nontypeable Haemophilus influenzae (NTHi). Presented at 9th Intl. Symp. Recent Adv. in Otitis Media.
• Bruggeman, M.E., McGillivary, G., Mason, K.M., Munson Jr., R.S. Bakaletz, L.O., Poster Presenter. 2007. Microbeinduceddysregulation of expression of mucosal antimicrobial peptides influences colonization of the chinchilla upper respiratory tract by nontypeable Haemophilus influenzae. Presented at 107th General Mtg., Am. Soc. for Microbiol.
• Mason, K.M., Zhang, Y., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2003. A mutation in the sap operon attenuates nontypeable Haemophilus influenzae (NTHI) survival in a chinchilla model of otitis media. Presented at 103rd General Mtg., Am. Soc. Microbiol.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2003. Use of differential fluorescence induction to identify site-specific nontypeable Haemophilus influenzae (NTHI) gene expression in a chinchilla model of otitis media. Presented at 8th Intl. Symp. Recent Adv. in Otitis Media,.
• Mason, K. Kesty, N., Vemulapalli, S., Horstman, A., Kuehn, M., Poster Presenter. 2001. Enterotoxigenic E. coli vesicles deliver toxin into epithelial cells. Presented at Cold Spring Harbor Microbial Pathogenesis and Host Response,. Cold Spring Harbor, NY, USA. (October)
• Mason, K.M., Hill, S.R., Munson Jr., R.S., , R.S. Jr., Bakaletz, L.O., Poster Presenter. 2006. Exposure of nontypeable Haemophilus influenzae (NTHI) to antimicrobial peptides results in rapid development of a resistant phenotype that is dependent upon the sap transporter. Presented at 106th General Mtg., Am. Soc. for Microbiol.
• Mason, K.M., and Bakaletz, L.O., Poster Presenter. 2008. The Sap transporter is critical to survival strategies by nontypeableHaemophilus influenzae (NTHi). Presented at 108th General Mtg., Am. Soc. for Microbiol.
• Kesty, N., K. Mason and M. Kuehn, Poster Presenter. 2003. Heat labile enterotoxin acts as an adhesin and entry mechanism for outer membrane vesicles produced by Enterotoxigenic E. coli. Presented at Gordon Research Conference: Microbial Adherence and Signal Transduction.
• Marshall, J.M., Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2007. The Sap transport systeminner membrane permease of nontypeable Haemophilus influenzae (NTHI) mediates potassiumacquisition in conjunction with antimicrobial peptide resistance. Presented at 107th General Mtg., Am.Soc. for Microbiol.
• Leimbach, C.F., Raffel F.K. and Mason K.M., Poster Presenter. 2009. Tracking the transport and fate of antimicrobialpeptides in nontypeable Haemophilus influenzea (NTHI). Presented at General Mtg., Am. Soc.for Microbiol.
• Raffel, F.K. and Mason K.M., Poster Presenter. 2010. The multifunctional Sap transporter is required for commensalhostcell homeostasis. Presented at 110th General Mtg., Am. Soc. for Microbiol.
• Mason, K.M., Bruggeman, M.E., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2004. Heme regulates sap operon expression in nontypeable Haemophilus influenzae (NTHI) and confers resistance to antimicrobial peptides. Presented at 11th Ann. Midwest Microbial Pathogenesis Mtg.
• McBroom, A., S. Bauman, N. Kesty, K. Mason and M. Kuehn., Poster Presenter. 2005. Bacterial outer membrane vesicles - Biogenesis and host cell interactions. Presented at Cold Spring Harbor Microbial Pathogenesisand Host Response. Cold Spring Harbor, NY, USA.
• Mason, K.M, Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2004. The Sap operon is required for nontypeable H. influenzae (NTHI) survival in a chinchilla model of otitis media. Presented at 104th General Mtg.,Am. Soc. Microbiol.
• Mason K.M., Bruggeman, M.E., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2005. The sap system is required for resistance to antimicrobial peptides and is differentially regulated in vivo in a superinfection model of otitis media. Presented at 105th General Mtg., Am. Soc. for Microbiol.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2006. The nontypeable Haemophilus influenzaeSap transporter provides a mechanism of antimicrobial peptide resistance. Presented at 13th Ann. Midwest Microbial Pathogenesis Mtg.
• Leimbach, C.F., Raffel F.K. and Mason K.M., Poster Presenter. 2009. Special Ops: tracking the transport and fate ofantimicrobial peptides in nontypeable Haemophilus influenzea. Presented at 16th Ann Midwest MicrobialPathogenesis Mtg.
• Hong, W., Mason, K.M., Jurcisek, J.A., Novotny, L.A., Bakaletz, L.O., Swords, W.E., Poster Presenter. 2007. Role of lipooligosaccharides in establishment of stable biofilm communities of nontypeable Haemophilus influenzae strain 86-028NP in a chinchilla model of otitis media. Presented at 4th ASM Conference on Biofilms.
• Kesty NC, Mason KM and Kuehn MJ, Poster Presenter. 2001. Enterotoxigenic Escherichia coli (ETEC) heatlabile enterotoxin (LT) mediates binding and internalization of outer-membrane vesicles by host cells. Presented at 101st General Mtg., Am. Soc. Microbiol.
• McGillivary, G., Mason, K.M., Jurcisek, J.A., Peeples, M.E. and Bakaletz, L.O., Poster Presenter. 2009. NontypeableHaemophilus influenzae colonization of the upper airway is augmented by RSV-induceddysregulation of expression of a mucosal beta-defensin. Presented at 109th General Mtg., Am. Soc.for Microbiol.
• Kuehn M, Mason K, Kesty N and Horstman A, Poster Presenter. 2000. Toxic Outer Membrane Vesicles Secreted by Enterotoxigenic E. coli. Presented at Gordon Research Conference: Bacterial Cell Surfaces. New London, NH, USA.
• Mason, K.M., and Bakaletz, L.O., Poster Presenter. 2008. The Haemophilus influenzae periplasmic Sap protein isessential for both antimicrobial peptide resistance and heme utilization. Presented at HINMAX 2008.1st Intl. Workshop on Haemophilus influenzae and Moraxella catarrhalis. Beurs World Trade Center. Rotterdam, The Netherlands.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2005. The sap operon is a major virulence determinant of NTHI-induced acute otitis media and is differentially regulated by antimicrobial peptides. Presented at Fifth Extraordinary Intl. Symp. Recent Adv. in Otitis Media.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2007. SapA, the sap operon periplasmic binding protein, binds heme and mediates iron homeostasis in nontypeable Haemophilus influenzae(NTHI). Presented at 107th General Mtg., Am. Soc. for Microbiol.
• Mason KM, Bigley NJ and Fink PS, Poster Presenter. 1997. Staphylococcal enterotoxin B (SEB) primes CD8+ interferon-? (IFN-?) secretion in response to bacteria. Presented at 97th General Mtg., Am. Soc.Microbiol.
• Novotny, L.A., Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2004. Construction and evaluation of lux-expressing Haemophilus influenzae for use in chinchilla models of otitis media. Presented at 104th General Mtg., Am. Soc. for Microbiol.
• Szelestey, B.R., Justice S.S., and Mason K.M., Poster Presenter. 2009. Morphological plasticity during hemestarvation and biofilm development in nontypeable Haemophilus influenzae (NTHI). Presented at 109thGeneral Mtg., Am. Soc. for Microbiol.
• Shelton, C.L., Raffel, F.K., Beatty, W.L., Johnson, S.M. and Mason, K.M.. 2011 (May 31). Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus. PLoS Pathogens. [Peer Reviewed] (First submission)
• Mason, K.M., Raffel F.K. and Szelestey B.R., Poster Presenter. 2008. The Haemophilus influenzae Sap proteins areessential for both antimicrobial peptide resistance and heme utilization. Presented at International Pasteurellaceae Society 2008 Meeting. Sorrento, Italy.
• Szelestey, B.R., Justice S.S., and Mason K.M., Poster Presenter. 2009. Morphological plasticity during hemestarvation and biofilm development in nontypeable Haemophilus influenzae (NTHI). Presented at 109th General Mtg., Am. Soc. for Microbiol.
• Mason, K.M., Zhang, Y., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2003. A mutation in the sap operon attenuates nontypeable Haemophilus influenzae (NTHI) survival in a chinchilla model of otitis media. Presented at 103rd General Mtg., Am. Soc. Microbiol.
• Jurcisek, J.A., Mason, K.M., and Bakaletz, L.O., Poster Presenter. 2008. Sub-lethal concentrations of antimicrobial7peptides alter biofilm formation by nontypeable Haemophilus influenzae (NTHi). Presented at 108thGeneral Mtg., Am. Soc. for Microbiol.
• Wallace, S., Kuehn, M., and Mason, K.M., Poster Presenter. 2009. Unraveling the biological relevance of nontypeableHaemophilus influenzae B.O.M.Bs. Presented at 16th Ann. Midwest Microbial Pathogenesis Mtg.
• McGillivary, G., Mason, K. M., Bevins, C.L., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2005. Characterization of two mucosal antimicrobial peptides in a chinchilla model of otitis media. Presented at Gordon Research Conference, Antimicrobial Peptides.
• Mason KM, Bigley NJ and Fink PS, Poster Presenter. 1997. Staphylococcal enterotoxin B (SEB) primes CD8+ interferon-? (IFN-?) secretion in response to native bacterial antigens. Presented at Cold Spring Harbor Lab. Mtg. On Microbial Pathogenesis and Host Response,.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2003. The sap operon confers resistance to antimicrobial peptides and is required for nontypeable Haemophilus influenzae (NTHI) survival in a chinchilla model of otitis media. Presented at 10th Ann. Midwest Microbial Pathogenesis Mtg.
• Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2002. Identification of nontypeable Haemophilus influenzae (NTHi) genes induced in vivo by differential fluorescence induction in a chinchilla model of otitis media. Presented at 102nd General Mtg., Am. Soc. Microbiol.
• Bruggeman, M.E., Mason, K.M., Munson Jr., R.S., Bakaletz, L.O., Poster Presenter. 2005. Nontypeable Haemophilus influenzae respond to micro-environmental cues to mediate an antimicrobial peptide-resistant phenotype. Presented at Fifth Extraordinary Intl. Symp. Recent Adv. in Otitis Media.
• Raffel, F.K. and Mason K.M., Poster Presenter. 2009. The multifunctional Sap transporter is required for commensalhostcell homeostasis. Presented at 16th Ann. Midwest Microbial Pathogenesis Mtg.