SJIF IMPACT FACTOR (2015): 5.79 CRDEEP Journals International Journal of Life Sciences Sikander Ali et. al., Vol. 6 No. 3 ISSN: 2277-193x Online version available at: www.crdeepjournal.org/ijls 96 International Journal of Life Sciences. Vol. 6 No. 3. 2017. Pp. 96-103 ©Copyright by CRDEEP Journals. All Rights Reserved Review Paper From Simple to its Extreme: Proteases Serving as Innovative Bacterial Weapon Sikander Ali; Muhammad Zain Ul Abbdin; Muhammad Faiq Ali and Waqas Ali Awan Institute of Industrial Biotechnology, Government College University, Lahore, Pakistan. Introduction Proteases are group of enzymes that function as protein degraders. The most commonly known function of protease is digestion of protein components of organic matter. Most of the bacteria especially saprotrophic bacteria use proteases to digest or decay organic matter. However, proteases are also a very useful tool to bring about normal cellular functions. But it could be regarded as innovation after that some of bacteria had been reported to use protease a destructive weapon and a very important virulent factor. So, for bacteria the protease is something more than just degrading protein content. Bacteria have moulded this protein digester to perform number of different cellular functions. For instance it regulates signal transmission through cell membrane and play role in quality control of cellular proteins. Protease also regulates protein secretions and maintains cell homeostasis. Furthermore, Proteases are also reported to help proper bacterial motility by ensuring normal biosynthesis of flagella. Proteases play direct role in signal transductions of a bacterial cell. Site-2 proteases (S2Ps) are common in bacteria and known to participate in different pathways which share the requirement for proteolysis of a transmembrane protein [3]. In this context S2Ps can be defined as multipass transmembrane proteins bearing a conserved zinc metalloprotease active site within a transmembrane domain while a motif within another transmembrane domain [1], [2]. The S2Ps of B. subtilis (YluC and SpoIVFB) and E. coli (RseP) have been intensely studied and are the best understood in terms of signal transduction mechanism, upstream activating signals along with downstream regulons. Further investigation of S2Ps in bacterial pathogens has revealed roles for S2Ps in sensing host signals and regulating virulence gene expression during infection period [3]. Generally, the signalling cascades in which S2Ps participate follow the same general pathway. For example, site-1 protease usually cleaves extra cytoplasmic segment of the transmembrane substrate in response to inducer signal. This site-1 cleavage is instantly followed by cleavage of substrate present with in membrane by S2P, So it results liberating the cytosolic fragment of the substrate. Normally, the fragment released into the cytosol by the S2P cleavage is a transcriptional regulator [3]. In quality control of cellular proteins FtsH is a membrane bounded protease with N-terminal part embedded in transmembrane along with a cytosolic region comprising of an AAAþ ATPase and a Zn2þ metalloprotease. Enzyme FtsH is known to degrade number different short lived proteins and to degrade proteins that are misassembled in membrane [4]. Proteases also take part in control of cell secretions. A Gram negative pathogen Salmonella typhimurium, causative agent gastroenteritis in humans colonizes the small intestine. S. typhimurium mutants that lack Lon protease was unable to colonize. Salmonella pathogenicity island 1, SPI1 has been found to have ability to induce apoptosis in macrophages and enhanced ability to invade epithelial cells [5], [6]. Type III secretion system that is encoded by SPI1 is critical [7]. The SPI1 system composed of many proteins that arrange to form a specific needle shaped structure to inject effector proteins in cytosol of host. In host actin cytoskeleton is rearranged by these injected proteins helping Article history Received: 30-05-2017 Revised: 14-06-2017 Accepted: 18-06-2017 Corresponding Author Sikander Ali Institute of Industrial Biotechnology, Government College University, Lahore, Pakistan. Abstract Proteases are group of enzymes that catalyse protein digestion. Large numbers of bacterial proteases perform different roles in bacteria. Most of bacteria especially saprotrophic bacteria uses proteases to digest organic matter. Somehow bacteria proved to be smart enough to cash protein digesting ability of proteases to execute different cellular functions. These normal cellular functions include protein digestion (pepsin), quality control (FtsH), control of cell secretions (Lon), regulation of flagella synthesis (clpXP) and signal transduction (YluC). However, some bacteria proved to be even smarter as they managed to use proteases as an effective weapon. As a bacterial weapon these have potential to disfigure host tissues (glutamylen- o-peptidase SspA) confront host defences (ScpC) and to escalate infection (V8 serine protease). Collectively these functional shifts are symbol of bacterial innovation. All these mechanism used by bacteria can be exploited and can pave way in antibiotics production. Keywords-Proteases, Protein digestion, Quality control, Signal transduction, Disfigure host tissues, Confronting defenses, Escalating infection.