Hongwei D. Yu, Ph.D.

Professor and Research Cluster Coordinator
Department: Biochemistry and Microbiology; Pediatrics
Research Cluster: Infectious and Immunological Diseases
Office: BBSC 435-R | Laboratories: BBSC 428 and 429
Phone: (304) 696-7356 | Fax: (304) 696-7207
E-mail: yuh@marshall.edu


Research Interests

Two projects are on-going in the Yu laboratory.

Regulation of Alginate Biofilms in Pseudomonas aeruginosa

P. aeruginosa is a ubiquitous bacterium that readily forms a biofilm by producing an exopolysaccharide capsule called alginate.  The overproduction of alginate (mucoidy) is a virulence factor that allows greater adhesion to lung epithelial cells, as well as protection from antibiotics and the host’s immune system.  Individuals afflicted with cystic fibrosis (CF) are particularly susceptible to P. aeruginosa infections.  The current paradigm regarding alginate overproduction is that mutations in the transmembrane protein MucA result in the activation of the alginate biosynthetic operon.  However, there are clinical isolates that are highly mucoid but possess a wild-type MucA.  The molecular mechanism responsible for the mucoid phenotype in these clinical isolates is not fully understood.  Recently, we and others found that alginate overproduction in the mucA+ strains seems to be regulated by a series of proteases, AlgW, MucP, ClpX, ClpP, and ClpP2 (Figure 1).  Elucidation of this novel pathway will lead to better understand the initial colonization factors, and development of therapeutics to improve the quality of life for individuals with CF.

Figure 1 - Alginate Production Model

Figure 1. Schematic outlining the model of regulated proteolysis of anti-sigma factor MucA for mucoid conversion in strains with the wild type mucA. There are two envelope proteases AlgW and MucP that require activation prior to degradation of MucA. MucE can activate AlgW to degrade the C-terminal portion of MucA. Inactivation of MucD can bypass AlgW by directly activating MucP to degrade MucA. ClpXP and ClpP2 are involved in degradation of cyto-MucA.

Modeling Bacterial Lung Infections

Most of bacterial lung infections initiate with the colonization of the upper respiratory tract. Aspiration of oropharyngeal secretions containing colonizing bacteria deep into the lung allows for the establishment of lower respiratory tract infections. Cystic fibrosis broncho-pneumonia is characterized by infections in the lower respiratory tract, which is otherwise a sterile environment.  We are using an inhalation exposure system to deposit the airborne pathogens into distal airways of the mouse lungs, causing the establishment of acute pneumonia (Figure 2).  This model is being utilized to study the host and bacterial factors that confer increased susceptibility to lung infections by P. aeruginosa, Staphylococcus aureus and Klebsiella pneumonia. The goal of this project is to better understand the etiology of bacterial lung infections using the mouse model for the development of novel therapeutics.

Figure 2. Inhalation System Model

Figure 2. (A). The inhalation exposure system is the infection mouse model to be used for the current study. This is a whole-body bacterial aerosol-based infection model where artificially generated bacterial aerosols are evenly introduced, without anesthesiat. (B). Schematic diagram of the aerosol inhalation machine system. Utilizing a negative pressured system powered by a vacuum pump at the end of the arrangement, room air is passed through a HEPA filter (#1) before entering the system. A compressor produces the air pressure needed to aerosolize the bacterial suspension, as shown in the inset. A valve controls the flow of the compressed air, regulating the level of aerosolization. The main air is responsible for carrying the aerosol from the nebulizer-Venturi unit to the inhalation chamber. Exhaust air with bacteria is filtered (HEPA filter #2) and incinerated. UV lamps destroy residual bacteria within the chamber as well as on the animal coats.


Selected Publications

Damron, F. H, J. P. Owings, Y. Okkotsu, J. J. Varga, J. R. Schurr, J. B. Goldberg, M. J. Schurr, and H. D. Yu. 2012. Analysis of the Pseudomonas aeruginosa Regulon Controlled by the Sensor Kinase KinB and Sigma Factor RpoN. J Bacteriol. 194(6):1317-30. PMID: 22210761

Damron, F. H., M. R. Davis Jr., T. R. Withers, R. K. Ernst, J. B. Goldberg, G. Yu, and H. D. Yu. 2011. Vanadate and triclosan synergistically induce alginate production by Pseudomonas aeruginosa strain PAO1. Mol. Microbiol. 81: 554-570. PMID: 21631603.

Damron, F. H., and H. D. Yu. 2011. Pseudomonas aeruginosa MucD regulates alginate pathway through activation of MucA degradation via MucP proteolytic activity. J. Bacteriol.193:286-291. PMID: 21036998

Damron, F. H., D. Qiu, and H. D. Yu. 2009. Pseudomonas aeruginosa sensor kinase KinB negatively controls alginate production through AlgW-dependent MucA proteolysis. J. Bacteriol. 191: 2285-2295. PMID: 19168621

Qiu, D., F. H. Damron, T. Mima, H. P. Schweizer, and H. D. Yu. 2008. PBAD-based shuttle vectors for functional analysis of toxic and highly-regulated genes in Pseudomonas and Burkholderia spp. and other bacteria. Appl. Environ. Microbiol.74: 7422-7426. PMID: 18849445

Qiu, D., V. M. Eisinger, N. E. Head, G. B. Pier and H. D. Yu. 2008. ClpXP proteases positively regulate alginate over-expression and mucoid conversion in Pseudomonas aeruginosa. Microbiol. 154: 2119-2130. PMID: 18599839

Qiu, D., V. M. Eisinger, D. W. Rowen, and H. D. Yu. 2007. Regulated proteolysis controls mucoid conversion in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 104: 8107-8112. PMID: 17470813

Wilson, K. R., J. M. Napper, J. Denvir, V. E. Sollars, and H. D. Yu. 2007. Defect in early lung defense against Pseudomonas aeruginosa in DBA/2 mice is associated with increased pulmonary inflammation and reduced bactericidal activity in naive macrophages. Microbiol. 153: 968-979. PMID: 17379707.

A complete list of publications from the Yu lab can be found at the following link:



1996-99 Post-doc, Microbial Pathogenesis University of Michigan Medical School
Ann Arbor, MI
1994-96 Post-doc, Microbial Pathogenesis UT Health Science Center
San Antonio, TX
1990-94 Ph.D., Molecular Pathogenesis University of Calgary
Alberta, Canada

Selected Patents

Yu, H. D., and D. Qiu. 2007. Methods of Detecting and Controlling Mucoid Pseudomonas Biofilm Production, USPTO No. 7,781,166

Laboratory Personnel

T. Ryan Withers, BMS Ph.D. Candidate (WVU and Johns Hopkins University)

Yeshi (Jake) Yin, Ph.D. Postdoctoral fellow (Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences)

Hongwei D. Yu, PI