Cystatin 9 (CST9) is a member of the type 2 cystatin superfamily, which consists of small, structurally conserved cysteine protease inhibitors. These proteins are found in various body compartments and fluids, where they play a crucial role in regulating proteolytic activities by inhibiting cysteine proteases such as cathepsins .
Cystatin 9 is a small protein with a molecular weight of approximately 18 kDa . It functions both intra- and extracellularly to maintain a balance between proteases and their inhibitors, which is essential for preventing excessive proteolytic activity that can lead to tissue damage . The inhibition of cysteine proteases by cystatins is vital for various physiological processes, including immune response modulation, inflammation regulation, and tissue remodeling .
Recombinant human cystatin 9 (rCST9) is produced using recombinant DNA technology, which involves inserting the gene encoding CST9 into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant form retains the functional properties of the native protein and is used in various research and therapeutic applications .
Recent studies have highlighted the potential of rCST9 as an immunomodulatory and antibacterial agent. For instance, rCST9 has been shown to protect against multidrug-resistant (MDR) bacterial infections, such as those caused by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae . In these studies, rCST9 modulated the host’s inflammatory response, reduced bacterial burden, and improved survival rates in infected mice .
Additionally, rCST9 has demonstrated protective effects against Francisella tularensis, a highly virulent bacterium. In vitro and in vivo experiments revealed that rCST9 decreased bacterial replication, induced autophagy in macrophages, and promoted anti-inflammatory and anti-apoptotic responses . These findings suggest that rCST9 could be a promising therapeutic candidate for treating bacterial infections and modulating excessive inflammatory responses.