Bakaletz, Lauren

Lauren O. Bakaletz, Ph.D., is Director of the Center for Microbial Pathogenesis, Columbus Children’s Research Institute and Professor of Pediatrics, The Ohio State University College of Medicine. Our laboratory’s research focus is attempting to understand the pathogenic mechanisms operational in the polymicrobial disease, otitis media (OM) (or middle ear infection). Specifically, we are interested in elucidating how upper respiratory tract viruses predispose the middle ear to invasion by any of the three predominant bacterial pathogens of OM. We are also interested in understanding how the mammalian host responds to each of these groups of microbes, particularly at the level of innate immunity, as well as determining how the bacteria involved (primarily nontypeable Haemophilus influenzae) defend themselves against these innate immune effectors. Using multiple approaches, we then attempt to identify potential molecular targets for the design, development and pre-clinical testing of vaccine candidates using an animal model of viral-bacterial superinfection that we developed. Our long-term goal is to develop novel methods to treat or preferably, to prevent, otitis media.

To date, the laboratory has extensively characterized one of these targets in particular, a nontypeable Haemophilus influenzae (NTHI) adhesin, defining its role in the pathogenesis of NTHI-induced OM as well as its contribution to the ability of NTHI to ascend a virus-compromised Eustachian tube from its colonization site in the nasopharynx.  Via concurrent epitope mapping efforts, a minimal focused region of the NTHI adhesin of interest (OMP P5-homologous adhesin), that contains both an adhesin binding domain as well as a protective epitope, was identified and incorporated into the design of two novel vaccine candidates.  Both vaccine candidates have now been extensively evaluated in preclinical vaccine trials using multiple rodent host model systems.

The laboratory has also collaborated with the Munson Lab at CCRI, to obtain and annotate the genome of a clinical isolate of NTHI which, when combined with multiple molecular techniques, has allowed the identification of several novel NTHI virulence determinants that are currently being analyzed further for both their role in pathogenesis as well as their potential utility as a vaccine candidate.  We are currently collaborating to study both type IV pili and oxidative stress in NTHI.  Through collaboration with the laboratories of Drs. Joan Durbin and Mark Peeples, both in the Center for Vaccines and Immunity at CCRI, we have developed murine and chinchilla models of RSV infection of the uppermost airway and are currently using these models to better understand RSV pathogenesis as well as to test viral vaccine candidates for efficacy in the chinchilla host.  We are also collaborating with the Partida-Sanchez Lab to analyze the role of dendritic cells during OM and its prevention via immunization.  Lastly, the Bakaletz Lab is collaborating with the laboratory of Dr. Samantha King to study pneumococcal deglycosylation of antimicrobial peptides.

Selected Publications
McGillivary, G., Ray, W.C., Bevins, C.L., Munson Jr., R.S., Bakaletz, L.O.  (2007). A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media.  Mol Immunol, 44(9):2446-58.

Harrison, A., Ray, W.C., Baker, B.D., Armbruster, D.W., Bakaletz, L.O., Munson Jr., RS.  (2007). The OxyR regulon in nontypeable Haemophilus influenzae.  J Bacteriol, 189(3):1004-12.

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):958-65.

Jurcisek, J.A., Bakaletz, L.O.  (2007). Biofilms formed by nontypeable Haemophilus influenzae in vivo contain both dsDNA as well as type IV pilin protein.  J Bacteriol, 189(10):3868-75.

Jurcisek, J.A., Bookwalter, J.E., Baker, B.D., Fernandez, S., Novotny, L.A., Munson Jr., R.S., Bakaletz, L.O.  (2007). The PilA protein of nontypeable Haemophilus influenzae plays a role in biofilm formation, adherence to epithelial cells and colonization of the mammalian upper respiratory tract.  Mol Micro, 65(5):1288-99.

Jewell, N.A., Vaghefi, N., Mertz, S.E., Akter, P., Peebles, R.S. Jr., Bakaletz, L.O.,  Durbin, R.K., Flano, E., Durbin, J.E.  (2007). Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo.  J Virol, 81(18):9790-800.

Luke, N., Jurcisek, J.A., Bakaletz, L.O., Campagnari, A. (2007). Contribution of Moraxella catarrhalis type-IV to nasopharyngeal colonization and biofilm formation.  Infect Immun, 75(12):5559-64.

Bakaletz, L.O. (2007). Bacterial biofilms in otitis media: evidence and relevance.  Pediatr Infect Dis J, 26(10 Suppl):S17-9.  

Bookwalter, J.E., Jurcisek, J.A., Gray-Owen, S.D., Fernandez, S., McGillivary, G., Bakaletz, L.O.  (2008). A carcinoembryonic antigen-related cell adhesion molecule 1 homologue plays a pivotal role in nontypeable Haemophilus influenzae colonization of the chinchilla nasopharynx via the outer membrane protein P5-homologous adhesin.  Infect Immun, 76(1):48-55.

Novotny, L.A., Partida-Sanchez, S., Munson Jr., R.S., Bakaletz, L.O.  (2008). Differential uptake and processing of an OMP P5-derived immunogen by chinchilla dendritic cells.  Infect Immun, 76(3):967-77.

Laboratory Personnel

Contact
Email:  Lauren.Bakaletz@nationwidechildrens.org 
Phone:  614-722-2915

The Research Institute at Nationwide Children’s Hospital
700 Children's Drive, W591
Columbus, OH  43205

Links

http://www.ccri.net/ccri/index.html
Dr. Bakaletz's Site at The Research Institute