The Role of Streptokinase as a Virulence Determinant of Streptococcus pyogenes – Potential for Therapeutic Targeting

Abstract

. (2012). The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting. Current Drug Targets, 13 (3), 297-307. The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies for disruption of streptokinase mediated plasminogen activation which could be employed to treat severe invasive S. pyogenes infections. AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome.These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein.Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies that disrupt streptokinase mediated plasminogen activation and could be employed to treat severe invasive S. pyogenes infections.3

Bacterial Plasminogen Receptors: Mediators of a Multifaceted Relationship

“…Commandeering the host plasminogen activation system is a common mechanism employed by a variety of bacteria [17–20]. The ability to acquire cell surface plasminogen is not host species restricted or limited to specific sites of infection.…”

A Key Role for the Urokinase Plasminogen Activator (uPA) in Invasive Group A Streptococcal Infection

“…This has inspired research to develop therapeutic inhibitors of bacterial plasminogen activation and recruitment [2], [3], [4], [5]. To be successful, such strategies require a comprehensive understanding of how bacteria interact with the host fibrinolytic system.…”

In Vivo Tracking of Streptococcal Infections of Subcutaneous Origin in a Murine Model

“…Because virulence of streptococcal pathogens is related to the expression of microbial virulence factors, including exotoxins (i.e., strep-tolysin O and S, streptococcal pyogenic exotoxin A and C), hyaluronidase, C5a peptidase, streptococcal chemokine protease, and SK, we evaluated streptococcal infections in a Pg-independent model of cutaneous infection, thereby testing whether activation of host Pg is strictly required for S. pyogenes virulence. One example of these Pg-independent disseminative virulence factors is the cysteine protease SpeB, which is found in all GAS strains and cleaves cytokine precursors, immunoglobulins, and immune system-associated receptors [31]. Inactivating SpeB decreases the GAS dissemination, potentially through inactivation of SK causing modulation of Pg activation [32, 33].…”

“…Inactivating SpeB decreases the GAS dissemination, potentially through inactivation of SK causing modulation of Pg activation [32, 33]. Streptococcal deoxyribonuclease, called strepto-dornase, and phage-acquired DNases function to clear the infection site to aid in dissemination and immune system evasion [31]. Therefore, we sought to determine if these factors, along with others, are sufficient to allow for the spread of the S. pyogenes infections in the absence of a productive SK-Pg system [34].…”