This project aims to define how Moraxella catarrhalis (Mcat) senses quorum signals produced by other organisms. Mcat is among are the predominant agents causing otitis media and other opportunistic airway infections, and our data show that Mcat can sense dihydroxypentanedione (DPD) quorum signals produced by Haemophilus influenzae. We hypothesize that Mcat """"""""eavesdrops"""""""" on quorum signal molecules produced by other pathogens, resulting in increased production of the Hag adhesin and concomitant increases in biofilm resistance properties. In order to address this hypothesis we will complete the following Specific Aims:
Specific Aim 1 : To identify determinants of DPD uptake by Mcat.
Specific Aim 2. To define the determinants of DPD response in Mcat.
Specific Aim 3. To define importance of quorum signal eavesdropping in Mcat persistence and virulence during experimental otitis media. Otitis media is among the most common pediatric infectious diseases, affecting the majority of children and accounting for billions of dollars in total health care costs per year. It is clear that a significant proportion of these infections are caused by Mcat, for which there is no currently licensed vaccine. Unfortunately, our ability to treat these infections is increasingly limited by the continued emergence of antibiotic-resistant bacterial strains. The results of these studies will provide significant insight into mechanisms for the persistence of Mcat in the polymicrobial infections that represent the majority of cases. Such insights could be pivotal advances in the design of new means for treatment of chronic Mcat infections.
Otitis media is a major common and costly pediatric illness worldwide, accounting for billions of dollars per year in total economic impact. Otitis media infections are the leading reason for pediatric office visits, new antibiotic prescriptions, and surgical instillation of tympanic drain tubes to relieve chronic and recurrent otitis media is the most commonly performed surgical procedure in the U.S. and it is clear that Moraxella catarrhalis is a major cause of these infections. It is thus of great importance to improve our knowledge of M. catarrhalis biology and pathogenesis.
|Barenkamp, Stephen J; Chonmaitree, Tasnee; Hakansson, Anders P et al. (2017) Panel 4: Report of the Microbiology Panel. Otolaryngol Head Neck Surg 156:S51-S62|
|Kyd, Jennelle M; Hotomi, Muneki; Kono, Masamitsu et al. (2017) Panel 5: Immunology. Otolaryngol Head Neck Surg 156:S63-S75|
|Reimche, Jennifer L; Kirse, Daniel J; Whigham, Amy S et al. (2017) Resistance of non-typeable Haemophilus influenzae biofilms is independent of biofilm size. Pathog Dis 75:|
|Murrah, Kyle A; Turner, Roberta L; Pang, Bing et al. (2015) Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media. Pathog Dis 73:1-8|
|Perez, Antonia C; Pang, Bing; King, Lauren B et al. (2014) Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo. Pathog Dis 70:280-8|
|Swords, W Edward (2012) Quorum signaling and sensing by nontypeable Haemophilus influenzae. Front Cell Infect Microbiol 2:100|
|Swords, W Edward (2012) Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections. Front Cell Infect Microbiol 2:97|
|Armbruster, Chelsie E; Pang, Bing; Murrah, Kyle et al. (2011) RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP. Mol Microbiol 82:836-50|
|Armbruster, Chelsie E; Swords, W Edward (2010) Interspecies bacterial communication as a target for therapy in otitis media. Expert Rev Anti Infect Ther 8:1067-70|
|Weimer, Kristin E D; Armbruster, Chelsie E; Juneau, Richard A et al. (2010) Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis 202:1068-75|