The uropathogen K

The uropathogen K. pneumoniae possesses several surface components that aid infection in the human urinary tract. The surface components, known as virulence factors, enable attachment and persistence which are essential in the process of infection and allow the uropathogen to remain in the urinary tract to cause infection. Without attachment and persistence, the uropathogen would be removed from the system by various processes such as the immune response and natural emptying of the bladder. In addition, attachment can further aid infection as it can trigger uptake inside cells, exposing new areas for colonisation (reference). Through studies conducted, the key surface components involved in pathogenic mechanisms that enable attachment and persistence that permit urinary tract infections have been identified.
Firstly, a key surface component that K. pneumoniae possesses that enables attachment and persistence in the human urinary tract is a surface capsule. The capsule consists of a polysaccharide matrix and is regarded to be the most influential virulence factor of K.pneumoniae as it acts to assist the uropathogen in evading the host immune system, thus enabling persistence in the urinary tract (Martin and Bachman 2018). Immune evasion is essential in persistence as without evasion then the uropathogen would be removed from the urinary tract by the host immune system, thus preventing infection. Upon recognition of the pathogen, the host immune system employs multiple mechanisms to remove the uropathogen; for example, it signals for immune cells to phagocytose the pathogen and also causes lysis via the complement system and antimicrobial peptides. However, the surface capsule defends and protects the uropathogen against these mechanisms by binding antimicrobial peptides and complement components. It is thought to interfere with the complement system by the capsule functiong as a cover, shielding the antibody epitopes on the bacterial surface, and therefore potentially preventing the complement activation completely (Doorduijn et all 2016). Furthermore, the surface capsule prevents activation of the early immune response which allows the uropathogen to persist in the urinary tract. In addition to this, the surface capsule also decreases the inflammatory response by shielding liposaccharides from immune cell receptors through activating a NOD-dependent pathway (Paczosa and Mecsas 2016). It has been proven that the surface capsule is a critical feature in enabling attachment and persistence in the urinary tract. Through studies conducted, it was proven that K. pneumoniae strains that are capsulated are significantly less likely than strains that are not to be removed from the urinary tract by immune cells (figure 1), highlighting the surface capsule as an essential surface feature for K.pneumoniae to persist in the urinary tract.
Another surface feature of K.pneumoniae that enables attachment and persistence in the urinary tract are pili (fimbraie). K. pneumoniae establishes a UTI through the use of pili as they enable attachment to the host, assist in gaining access to host tissues and promote biofilm formation, therefore encouraging attachment and persistence in the human urinary tract (Flores-Mireles et al 2015). Examples of the pili K. pneumoniae produce are type 1 and type 3 pili; types of pili known as chaperone-usher pathway (CUP) pili that are responsible for attachment via the chaperone-usher pathway. Type 1 fimbriae produced carry out their adhesive function through utilisation of the adhesin FimH which is located at the tip of the pili. Glycoproteins such as mannose-containing glycoproteins located on the surface of the urinary tract are recognised by FimH which initiates a cascade involving Rho GTPases to bring about attachment and colonisation of the bladder cells via a zippering mechanism that engulfs the uropathogen (Flores-Mireles et al 2015). Internalisation facilitates persistence in the urinary tract as it presents the uropathogen protection from immune attack and also provides extra nutrients. The importance of the attachment and colonisation via type 1 and type 3 fimbraie has been demonstrated through several studies. For example, the ability of K. pneumoniae with mutated fimbriae to cause an UTI was assessed in studies in which mouse bladders were infected with the wild type or a fimbrial mutant (Murphy et al 2013). Using these experiments, it was shown that both type 1 and type 3 fimbriae function to enable colonisation and persistence as all pathogens with mutated fimbriae were significantly less successful in colonising the urinary tract than wild type pathogens (figure 1). Furthermore, the fimbriae also have an additional role in the persistence of the uropathogen in the urinary tract as they are regulated by phase variation which allows the uropathogen to avoid recognition by the immune system.