Urinary Bladder Matrix Protects Host in a Murine Model of Bacterial-Induced Lung Infection

Abstract

The extracellular matrix (ECM) is composed of a complex mixture of structural and functional macromolecules that are important during growth, development, and wound repair. In this study, we seek to determine if an ECM derived from the porcine urinary bladder, specifically urinary bladder matrix (UBM), can act to prevent bacterial infection in the context of lung injury. In this study, we examined a digested form of UBM, which prevented bacterial biofilm formed by both Gram-positive bacteria (GPB) such as methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and Gram-negative bacteria (GNB), including Pseudomonas aeruginosa (PA) and Klebsiella pneumoniae (KP) in vitro. Furthermore, exogenously administered UBM digest exhibited host protection from MSSA-, MRSA-, and PA-induced respiratory infection in a murine infection model. The protection against both GPB- and GNB-induced infection demonstrated by UBM suggests the antibacterial function is likely through biofilm prevention. In addition, two potential off the shelf UBM product forms (preformulated digested UBM and intact UBM particulate) showed significant protection from acute severe respiratory infection. Taken together, our results support further study of the use of UBM as an alternative treatment to attenuate bacterial-induced infection.

Impact Statement

Lung infection is a leading cause of human life lost to morbidity and/or mortality. This problem is exacerbated by the alarming emergence of increasingly antibiotic-resistant (AR) microorganisms worldwide and the lack of effective antimicrobials to overcome the AR bacterial infection. Urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue regeneration and remodeling in a variety of body systems. Our novel findings demonstrate that the preformulated UBM effectively protects the host from methicillin-resistant Staphylococcus aureus (MRSA)- and Pseudomonas aeruginosa-induced murine pneumonia and may provide a viable alternative/supplement for protection against respiratory AR bacterial infection.