The emergence of Pseudomonas aeruginosa as a potential threat in persistent infections can be attributed to the plethora of virulence factors expressed by it. This review discusses the various virulence factors that help this pathogen to establish an infection and regulatory systems controlling these virulence factors. Cell-associated virulence factors such as flagella, type IV pili and non-pilus adhesins have been reviewed. Extracellular virulence factors have also been explained. Quorum-sensing systems present in P. aeruginosa play a cardinal role in regulating the expression of virulence factors. The identification of novel virulence factors in hypervirulent strains indicate that the expression of virulence is dynamic and constantly evolving. An understanding of this is critical for the better clinical management of infections.
Magic spot synthetases are emerging targets to overcome persistence caused by stringent response. The ‘stringent response’ is a bacterial stress survival mechanism, which results in the accumulation of alarmones (also called Magic spots) leading to the formation of dormant persister cells. These ‘sleeper cells’ evade antibiotic treatment and could result in relapse of infection. This review broadly investigates the phenomenon of stringent response and persistence, and specifically discusses the distribution, classification, and nomenclature of proteins such as Rel/SpoT homologs (RSH), responsible for alarmone synthesis. The authors further explain the relevance of RSH as potential drug targets to break the dormancy of persister cells commonly seen in biofilms. One of the significant factors that initiate alarmone synthesis is nutrient deficiency. In a starved condition, ribosome-associated RSH detects deacylated tRNA and initiates alarmone synthesis. Accumulation of alarmones has a considerable effect on bacterial physiology, virulence, biofilm formation, and persister cell formation. Preventing alarmone synthesis by inhibiting RSH responsible for alarmone synthesis will prevent or reduce persister cells’ formation. Magic spot synthetases are thus potential targets that could be explored to overcome persistence seen in biofilms.
Unmanageable bleeding is one of the significant causes of mortality. Attaining rapid hemostasis ensures subject survivability as a first aid during combats, road accidents, surgeries that reduce mortality. Nanoporous fibers reinforced composite scaffold (NFRCS) developed by a simple hemostatic film-forming composition (HFFC) (as a continuous phase) can trigger and intensify hemostasis. NFRCS developed was based on the dragonfly wing structure's structural design. Dragonfly wing structure consists of cross-veins and longitudinal wing veins inter-connected with wing membrane to maintain the microstructural integrity. The HFFC uniformly surface coats the fibers with nano thickness film and interconnects the randomly distributed cotton gauge (Ct) (dispersed phase), resulting in the formation of a nanoporous structure. Integrating continuous and dispersed phases reduce the product cost by ten times that of marketed products. The modified NFRCS (tampon or wrist band) can be used for various biomedical applications. The in vivo studies conclude that the developed Cp NFRCS triggers and intensifies the coagulation process at the application site. The NFRCS could regulate the microenvironment and act at the cellular level due to its nanoporous structure, which resulted in better wound healing in the excision wound model.
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