Recombinant Pseudomonas aeruginosa Pseudolysin (lasB) protein [His-SUMO]

Pseudomonas aeruginosa (PA) is a Gram-negative pathogen, which in the clinic has come to be known as an opportunistic organism. Its quorum sensing mechanism controls biofilms and thus bacterium pathogenicity and resistance to antibiotics. PA is resistant to most antibiotics mainly due to the outer membrane barrier, efflux pump systems and the release of several enzymes, which make antimicrobial drugs useless. It can also degrade drugs by changing the antibiotic's target or producing antibiotic-degrading enzymes. In epidemiological studies, PA's pervasive presence in hospital settings is highly associated with cross-infections, with high levels of isolation in the very seriously ill from ventilator-associated pneumonia, urinary tract infections and burn infections.

PA possesses a large genome and a complex regulatory system, which together with its extensive arsenal of virulence factors, antibiotic resistance, and genetic/metabolic diversity under various environmental conditions, endows it with significant pathogenic capabilities. Elastase LasB is one of the extracellular virulence proteins secreted by PA, capable of degrading host tissue proteins, extracellular matrix (ECM), and components of the immune system. It leads to immediate harm to the cells of the host tissue, as well as severe impairment of the immune system, which makes infection possible to form and sustain. LasB (or pseudolysin) is an old-fashioned zinc-dependent metalloprotease whose 33,000-molecular weight gene encodes the lasB protein. It is a member of the thermolysin protease group and its three-dimensional conformation is almost identical to the thermolysin in Bacillus cereus (63%) in amino acid sequence. The catalytic site of LasB consists of a zinc finger structure, an active center, and a substrate binding site, where the binding sites for zinc and calcium ions are crucial for maintaining the stability of LasB's three-dimensional structure and its proteolytic activity.

Figure 1. Schematic representation of secreted LasB protein in Pseudomonas aeruginosa
(Source: Everett MJ, et al. 2021)

LasB participates in the hydrolysis of non-terminal peptide bonds in proteins and has multiple cleavage sites. It shows a preference for aromatic and aliphatic amino acids at the P1' position, while favoring acidic residues at the P2' position, which gives LasB a broad protein cleavage activity. Once secreted at the site of infection, LasB exerts its proteolytic effects, damaging a wide range of tissues and host immune defense components. The former targets the host's ECM and tight junctions between basal lateral cells, which exacerbates tissue damage and allows PA to acquire nutrients from these degraded components for sustained growth and enhanced invasiveness. The latter plays an immune regulatory role by degrading immune components such as cytokines, chemokines, immunoglobulins, and complement factors, creating a favorable environment for PA's survival. In addition to its extracellular effects, LasB also acts intracellularly by triggering pathways that initiate bacterial biofilm growth. Biofilms exhibit high resistance to host immune responses and antimicrobial agents, further intensifying the pathogenic effects and maintaining the infection.

Recombinant P. aeruginosa Pseudolysin (lasB) protein [His-SUMO]
Recombinant Pseudomonas aeruginosa Pseudolysin protein [His-SUMO]
Recombinant Pseudomonas aeruginosa Elastase lasB protein [His-SUMO]