NosP Detection of Heme Modulates Burkholderia thailandensis Biofilm Formation

Abstract

Aggregated bacteria embedded within self-secreted extracellular polymeric substances, or biofilms, are resistant to antibiotics and cause chronic infections. As such, they are a significant public health threat. Heme is an abundant iron source for pathogenic bacteria during infection; many bacteria have systems to detect heme assimilated from host cells, which is correlated with the transition between acute and chronic infection states. Here, we investigate the heme-sensing function of a newly discovered multifactorial sensory hemoprotein called NosP and its role in biofilm regulation in the soil-dwelling bacterium Burkholderia thailandensis, the close surrogate of Bio-Safety-Level-3 pathogen Burkholderia pseudomallei. The NosP family protein has previously been shown to exhibit both nitric oxide (NO)- and heme-sensing functions and to regulate biofilms through NosP-associated histidine kinases and two-component systems. Our in vitro studies suggest that BtNosP exhibits heme-binding kinetics and thermodynamics consistent with a labile heme-responsive protein and that the holo-form of BtNosP acts as an inhibitor of its associated histidine kinase BtNahK. Furthermore, our in vivo studies suggest that increasing the concentration of extracellular heme decreases B. thailandensis biofilm formation, and deletion of nosP and nahK abolishes this phenotype, consistent with a model that BtNosP detects heme and exerts an inhibitory effect on BtNahK to decrease the biofilm.

Amphiphilic Janus nanoparticles for nitric oxide synergistic photodynamic eradication of MRSA biofilms

“…1–5 Biofilms, formed by bacteria that adhere to surfaces and aggregate together within a matrix of extracellular polymeric substances (EPS), create a formidable barrier to effective anti-bacterial treatments and evade the host immune system. 6–10 The formation of biofilms further exacerbates the severity of MRSA infections. It is well demonstrated that the encapsulation of EPS creates an oxygen-deficient biofilm microenvironment, which can lead to anaerobic glycolysis.…”