Luanne Hall-Stoodley, Ph.D. Assistant Professor Microbiology and Immunology Assistant Professor, Center for Genomic Sciences, ASRI 320 East North Avenue Pittsburgh, PA 15212 Phone: 412-359-5016 Fax: 412-359-6995 Email: lstoodle@wpahs.org Ph.D., 1995, Montana State University, Bozeman, Montana

Keywords:

Biofilms, host-pathogen interactions, environmental mycobacteria, Streptococcus pneumoniae, Mycobacterium  tuberculosis, innate immunity

Research Interests:

My research interests are in biofilms and host pathogen interactions. 

• Biofilm development by pathogenic bacteria including Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus mutans and opportunistic environmental mycobacteria.
• Bacterial attachment/adhesion to host proteins (Mycobacterium  tuberculosis) and how these interactions affect adherence to airway epithelial cells.
• Interactions of pathogens with the host and innate immunity.
• Bacterial pathogen persistence.

Biofilms

Biofilms are matrix-enclosed microbial populations adherent to biological or non-biological surfaces, which represent an important, but incompletely understood mode of growth for bacteria.  Most bacteria in the natural environment grow in biofilms rather than as single planktonic (free swimming) cells.  Biofilms are dynamic, structurally complex biological communities.  Biofilm development represents a protected mode of growth that allows bacteria to survive in hostile environments and disperse to colonize new niches. These survival and propagative mechanisms have fundamental implications in the context of both environmental microbiology and in infectious disease (Hall-Stoodley et al. 2004.  Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews: Microbiology. 2(2): 95-108).

Pathogenic biofilms

Some pathogens are only known to exist in the human host.  S. pneumoniae is an important pathogen which causes localized respiratory infections as well as life-threatening systemic infections.  Pneumococcus is an important pathogen in otitis media (OM) in children.  OM with effusion (OME) has been hypothesized to be a biofilm infection because of its chronic clinical course and its recalcitrance to antibiotic treatment.  Recently, we have shown that several pathogens associated with OME, including S. pneumoniae, H. influenzae and Moraxella catarrhalis, are present in biofilms on the mucosal epithelium of the middle ear in children undergoing typanostomy tube placement for the treatment of chronic otitis media (Hall-Stoodley et al. 2006. J. Am. Med. Assoc. 296(2):202-211). These biofilms were characterized as clusters of pathogenic bacteria identified in situ by fluorescent in situ hybridization (FISH) and immunostaining.  I am particularly interested in investigating pneumococcal biofilms and how biofilm development may contribute to chronic disease such as OME. 

Recently, I have characterized pneumococcal biofilm development by six clinical strains of S. pneumoniae isolated from children with otitis media.  This work demonstrated that various strains were extremely heterogeneous in their biofilm ultrastructure, including the production of an EPS matrix.  These clinical isolates also exhibited differences in resistance to the antibiotic azithromycin. All isolates, however, increased the number of attached bacteria on a glass or polystyrene surface over the 6-8 day culture period, suggesting that S. pneumoniae biofilm development contributes to extended survival in surface-attached structures (Hall-Stoodley et al. “Clinical Strains of Streptococcus pneumoniae Exhibit Extensive Variability in  Biofilm Formation, Extracellular Carbohydrate Matrix Production, and Resistance to Antibiotic Treatment”, submitted). 

My research interests also include biofilm formation by environmental nontuberculous mycobacteria (NTM).  These opportunistic pathogens exist in the environment, outside animal hosts, as indigenous inhabitants of aqueous systems, including freshwater, estuarine and marine environments and municipal water distribution systems.  The transmission of these pathogens occurs from the environment (Hall-Stoodley and Stoodley.  2005. Biofilm formation and dispersal and the transmission of human pathogens. Trends in Microbiol. 13(1): 7-10).  Several mechanisms may make opportunistic pathogens in biofilms more likely to cause disease than planktonic organisms; however, their ability to accrue large numbers of bacterial cells that can be inhaled, ingested, or abraded into the skin of a host is a central factor.  Biofilm development by mycobacteria is well documented and relevant to their ability to persist in these oligotrophic environments.  More research needs to be done on pathogenic mycobacterial biofilms to investigate the mechanisms that these organisms use to colonize surfaces and cause persistent infections. 

Finally, I am also interested in Mycobacterium tuberculosis and have investigated the ability of M. tuberculosis to attach to human proteins that play a role in innate immunity.  My research has showed that M. tuberculosis quickly attached to surfactant protein A and fibronectin under shear conditions used to select for high-affinity robust binding interactions.  Fibronectin also increased the number of bacilli that adhered to human primary small airway epithelial cells.  These results suggest that fibronectin may increase bacilli adherence to epithelial cells in the lung and that these cells may play an additional role in pathogenesis (Hall-Stoodley et al. Mycobacterium tuberculosis Binding to Human Surfactant Proteins A and D, Fibronectin and Small Airway Epithelial Cells Under Shear. Inf. Immun. 74(6):3587-96).

Selected Publications:

1. Hall-Stoodley, L. and H.M. Lappin-Scott.  1998.  Biofilm formation by the rapidly growing non-tuberculous mycobacteria species Mycobacteria fortuitum.  FEMS Microbiological Letters, 168:79-84.
2. Hall-Stoodley, L., C.W. Keevil and H.M. Lappin-Scott.  1999.  Mycobacterium fortuitum and Mycobacterium chelonae form biofilms under high and low nutrient conditions.  J. Appl. Microbiol. Vol. 85: 60S-69S.
3. Stoodley, P., Hall-Stoodley, L. and H.M. Lappin-Scott.  2000.  Detachment, surface migration and other dynamic behavior in bacterial biofilms revealed by digital time-lapse imaging. Methods in Enzymology: Microbial Growth in Biofilms. Ed. R.J. Doyle. 337:306-319.
4. Stoodley, P., Wilson, S., Hall-Stoodley, L., Boyle, J.D., Lappin-Scott, H.M. and J.W. Costerton. 2001.  Growth and detachment of cell clusters from mature mixed species biofilms.  Appl. Env. Microbiol. Vol. 67, No. 12, p. 5608-13.
5. Hall-Stoodley, L. and P. Stoodley. 2002. Developmental regulation of microbial biofilms. Curr. Opin. Biotech. 13:228-233.
6. Fux, C.A., Stoodley, P. Hall-Stoodley, L. and W.J. Costerton. 2003. Bacterial biofilms - a diagnostic and therapeutic challenge. Expert Review of Anti-Infective Therapy. 1(4): 667-683.
7. Hall-Stoodley, L., Costerton, J.W., and P. Stoodley. 2004. Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews: Microbiology. 2(2): 95-108.
8. Post , J. C., Stoodley, P., Hall-Stoodley, L. and G. D. Ehrlich.  2004. The role of biofilms in otolaryngologic infections. Current Opinions in Otolargology and Head & Neck Surgery.  12(3):185-190.
9. Hall-Stoodley, L. and P. Stoodley.  2005.  Biofilm formation and dispersal and the transmission of human pathogens. Trends in Microbiol. 13(1): 7-10.
10. Stoodley, P., Kathju, S., Ze Hu, F., Erdos, G., Levenson, J.E., Mehta, N.S., Dice, B.L., Johnson, S.L., Hall-Stoodley, L., Nistico, L., Sotereanos, N.G., Sewecke, J.J.,  Post, J.C. and G.D. Ehrlich. 2005. Molecular and imaging techniques for bacterial biofilms in arthroplastic joint infections.  Clinical Orthopedics and Related Research. 437:31-40.
11. Braxton, E.E. Jr, Ehrlich, G.D., Hall-Stoodley, L., Stoodley, P., Veeh, R., Fux, C., Hu, F.Z., Quigley, M. and J.C. Post.  2005. Role of biofilms in neurosurgical device-related infections. Neurosurg Rev.  28;4:249-255.
12. Hall-Stoodley, L., Brun, O.S., Polshyna G.P. and L.P. Barker.  2006. Mycobacterium marinum Biofilm Formation Reveals Cording Morphology.  FEMS Microbiology Letters.  257:43-49.
13. Hall-Stoodley, L., Watts G., Crowther, Balagopal A, Torrelles, J.B., J., Robison-Cox, J., Bargatze, R., Harmsen, A.G., Crouch, E.C. and L. D. Schlesinger.  Mycobacterium tuberculosis binding to human surfactant proteins A and D, fibronectin and small airway epithelial cells under shear.  Inf. Immun. 74(6):3587-96
14. Hall-Stoodley, L., Hu, F., Gieseke, A., Nistico, L., Nguyen, D., Hayes, J., Forbes M., Greenberg, D., Dice, B., Burrows, A., Stoodley, P., Post, J.C., G. D. Ehrlich and J. Kerschner.  2006. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. [Preliminary Communication]  J. Am. Med. Assoc. 296(2):202-211. Rapid Publication.
15. Hall-Stoodley L., Nistico, L. Nguyen, D., Mershon, W.J., Hayes, J., Hu, F.Z.,  Post, J.C., Stoodley, P. and G.D. Ehrlich.  Clinical strains of Streptococcus pneumoniae exhibit extensive variability in biofilm formation, extracellular carbohydrate matrix production, and resistance to antibiotic treatment, J Bacteriol, submitted.