Adhesins

 One of the primary pathogenicity mechanisms of uropathogenic is adhesion to host cells, which is also the initial stage of infection establishment (Sarshar et al, 2022). Helped by fimbriae to P. mirabilis bacterial adherence (Hasan, 2020), fimbriae play a pivotal role in the virulence of P. mirabilis, serving as key adhesion structures that facilitate the bacterium’s interaction with host tissues. Characterized by their molecular specificity, enable P. mirabilis to adhere to and colonize various surfaces within the host, including urinary tract epithelial cells (Armbruster et al, 2018)

Motility

 The motility is the main virulence factor of P. mirabilis that influence in invading and spreading of infection in urinary tract parts . The infection begins in the periurethral region, enters the urethra, and proceeds to the bladder and other urinary system organs. (Hickling and others, 2017). The bacterium P. mirabilis is a flagellar peritrichous one (Fattorini et al, 2020). This microorganism is swarming, which indicates enhanced pathogenicity because of its heightened motility (Kotian et al, 2020).

Toxins and Enzymes

 A-Hemolysin

 Hemolysin is a toxin that penetrates the eukaryotic cell's target membrane and produces pores that cause ion efflux and cell disruption (Banerji et al,2021). Hemolysin promotes the growth of bacterial infections in the kidney, which leads to pyelonephritis in ascending UTIs. (Hasan et al, 2021)hemolysin also plays a crucial part in immune evasion. P. mirabilis employs various strategies to evade host defenses. By disrupting host cell membranes, hemolysin facilitates the spread of P. mirabilis within the host, allowing the bacteria to evade immune cells. Thus, contributing to the severity and persistence of infections. The multifaceted functions of hemolysin highlight its importance as a key virulence factor in the pathogenic strategy of P. mirabilis (Norsworthy and Pearson, 2017).

B-Urease

 Urease is a nickel metalloenzyme that catalyzes the hydrolysis of urea to ammonia and carbon dioxide , a highly water-soluble molecule , a virulence factor that is encoded by a phylogenetically diverse group of bacteria Specifically in P. mirabilis.(Norsworthy and Pearson, 2017) . The amalgamation of recent findings with prior fundamental research has illuminated the mechanisms by which this microorganism, and conceivably other urease-generating bacteria, effectively instigates and establishes urinary tract infections (Shahriar et al, 2022). To establish and maintain infections of the urinary tract and colonization of catheters, Proteus species must adjust to the catheterized urinary tract and produce a stash of firmly regulated virulence factors. Urease, which catalyzes stone formation in the kidney and bladder, is important in P. mirabilis pathophysiology (Hasan et al, 2021). This enzyme aids in the production of kidney and bladder stones and encrusting or obstructing the urinary tract (Armbruster et al, 2018)

Quorum Sensing of Proteus mirabilis

 Quorum Sensing is characterized as a system that is mediated by small chemicals that are generated intracellularly and either passively diffuse out of the cells or are actively released, allowing microorganisms to interact with their surroundings and control gene expression. These compounds are referred to as auto-inducers, or otherwise also known as Quorum Sensing Molecules QSMs. (Sharma et al, 2020). Bacteria in a biofilm can coordinate their actions through a communication mechanism known as quorum sensing (QS). A key function of Quorum Sensing (QS) is to control the synthesis of virulence factors. Simply, QS refers to the bacterial population’s communication system. To change the expression of virulence proteins, certain QS receptors can detect their homologous inducers produced by the same bacterial species or even by other species (Elfaky et al, 2023). Despite using different inducers and QS machinery, both Gram-positive and Gram negative bacteria use QS to modulate their pathogenicity (Thabit et al, 2022).

Swarming Motility

When P. mirabilis is added to agar surface, the bacteria grow in place for a time (which varies by medium, humidity, and temperature), differentiate into swarm cells, and move forward as a population. The ability of P. mirabilis to swarm as an organized group across solid surfaces was firstly characterized by Hauser in 1885. During the swarm process, P. mirabilis differentiates into very long (>50 µm), multinucleate, highly motile hyperflagellated cells (Al Otraqchi et al, 2021). At intervals, swarm cells slow down or stop movement and dedifferentiate into shorter rod-shaped cells in what is known as the consolidation phase. Repeated cycles of swarming and consolidation lead to the bull's-eye pattern (De Freitas, 2019). Reflecting this phenotype, P. mirabilis was named for the Greek God Proteus, who was able to change form at will to avoid questioning (Rommes et al, 2021) Figure (1)

fig1. The differentiation process of swarming process.(Chakkour M et al, 2024)

Various studies have been shown to try to understand how and why P. mirabilis swarms, even though much remains unknown. However, it has been absolutely demonstrated that flagella and chemotaxis are necessary for swarming (Matilla et al, 2022). Extracellular matrix components and fatty acids could also play roles in helping P. mirabilis to move across solid surfaces (Saleh, R.O. and Majeed, H.A ., 2021). Cell density may also play a role in the transition between swarming and consolidation phases and in the initiation of swarming (Liu et al, 2021)

Swarming motility initially depends on flagella function. The expression of flagellar biosynthesis genes is organized in a hierarchy, the top of which is directed by a master regulatory transcription factor ('master regulator'). Master regulators serve as an integration point for environmental signaling, activate flagellar gene expression, and govern the production of flagellar basal bodies. Flagellar assembly is complex and there are species-specific mechanisms of transcriptional and post-transcriptional regulation (Abdullah et al, 2022). Swarming behavior is partially controlled by rsbA gene product. rsbA may operate as a protein sensor of environmental circumstances, and rsbA was stimulated biofilm production and extracellular polysaccharide creation gene (Cortes-López et al, 2020).

References                                                                                                
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