A heparan sulfate proteoglycan binding protein and Light-Emitting Diodes-LEDs/Complex Electromagnetic Fields-CMFs technologies as innovative eco-sustainable strategies to counteract chronic wound infections associated to Staphylococcus pseudintermedius resistant strains: an interdisciplinary approach to animal-human health
Project The antimicrobial resistance-(AMR) phenomenon is a worldwide challenge involving human, animal and environmental health that strongly requires new sustainable intervention strategies. The focus of this project is twofold:
1) to address the knowledge of the physiopathology of S. pseudintermedius- (Sp) responsible of dynamic animal-human transmission and chronic wound-(CW) infections; 2) to study the antimicrobial/anti-virulence effects of sustainable combination consisting of recombinant protein-NK1 and novel technologies (Light-Emitting-Diodes-LEDs/Complex Electromagnetic Fields-CMFs) at low environmental impact. The project is in line with the “UN Agenda 2030” for Sustainable Development suggesting treatments to counteract the AMR based on natural compounds and novel technologies. Sp, an emerging zoonotic agent of canine origin, is an opportunistic pathogen causing diseases in dogs such as otitis externa, pyoderma, and wound infections. The worldwide spread of multidrug- resistant methicillin-resistant-Sp-(MRSP) and methicillin-susceptible- (MSSP) strains represents a health problem for both pets and humans. Biofilm formation is one of the most important virulence factors of Staphylococci, facilitating the bacterial colonization and hindering the treatments. Thus, the discovery of novel agents for treatment of Sp- associated and biofilm-related infections is highly warranted. The main objectives include: the elucidation of the molecular mechanisms involved in the Sp virulence; the identification of sustainable approaches to fight Sp infections in dog and human CWs. To address these objectives, MRSP and MSSP strains will be isolated from dog CWs and characterized for their virulence profiles. The selected strains, combined with the main microorganisms isolated in dog and human CWs, will be studied for their interactions in 3D gradient that mimics the CW spatial microbial distribution and environment, the Lubbock Chronic Wound Biofilm-(LCWB) model. The bacteria of Staphylococcus genus bind to the host cell surface or the extracellular matrix components, in which heparan sulfate proteoglycans- (HSPGs) play key roles. The recombinant synthesis of a natural splice variant of hepatocyte growth factor-(HGF), NK1, which is able to bind HSPGs and interfere with microbial adhesion and internalization into target cells, will be carried out. The role of novel technologies, LEDs and CMFs, as additional instruments to affect the antibiotic resistance/tolerance has emerged. Thus, NK1 alone or combined with novel technologies will be investigate against MRSP and MSSP in the LCWBs. To explore the molecular mechanism of NK1 action, and its capability to inhibit Sp infection in cellular tools and to modulate the cellular signaling pathways involved in the pathogenesis of Sp, will be also evaluated. The results will identify sustainable strategy to counteract CW infections associated to Sp strains both in dog and human populations.