Virulence factors of uropathogenic
Uropathogenic Escherichia coli (UPEC) strains are those that cause infections in the urinary tract. They acquired virulence factors which enable them to survive in the urinary tract and elicit pathogenicity. The virulence factors are classified into two categories: (i) bacterial cell surface virulence factors and (ii) bacteria secreted virulence factors. Adhesins, toxins and iron up-take systems are major groups of virulence factors. The variety of virulence factors of UPEC is presented in this chapter.
- extraintestinal E. coli
- uropathogenic Escherichia coli
- urinary tract infection
2. Adhesins of uropathogenic
Adhesins are adhesive organelles, notably fimbriae, that promote bacterial colonization. Some adhesins also promote bacterial invasion of the host cell. Adhesins are thought to be the most important virulence-associated molecules which function in UPEC pathogenicity. The adhesins can also directly trigger host and bacterial cell signaling pathways. They can also facilitate the delivery of other bacterial products to the host tissues . Prominent bacterial cell surface virulence factors, which play significant roles in UPEC pathogenicity include type 1 fimbriae ; Class I, Class II, and Class III of P-fimbriae [18, 19, 20]; Dr. family of adhesins for binding to the decay-accelerating factor (DAF) ; Curli fimbriae which functions as binding factor and biofilm producer ; and S-fimbriae [14, 23, 24]. Type 1 fimbriae have the most significant effects in UTIs as they enhance bacterial survival and growth, enhance inflammatory reaction at the mucosa, bacterial invasion, and control biofilm production . P-fimbriae have the second most prominent role in UPEC-associated pathogenesis of human ascending UTIs and pyelonephritis. They promote UPEC adherence to the matrix of the mucosa and tissues and trigger cytokine production [25, 26, 27, 28, 29, 30].
3. Toxins of uropathogenic
UPEC secrete several virulence toxins which are responsible for the damage of the host cells and host inflammatory response. α-hemolysin (HlyA) is the most virulent toxin produced by UPEC. The effects of HlyA in UTIs are dependent on its dosage produced by UPEC. At high concentration, HlyA destroys the erythrocytes and allow UPEC to break through the mucosal barriers, damage immune system, and depletes iron stores of the host [31, 32, 33, 34]. At low concentration, HlyA induces cell death in the bladder using proinflammatorycaspase-1/caspase-4. This causes kidney damage and scarring; oscillations of Ca2+; ascension and colonization of ureters and kidney parenchyma in the renal tubule epithelia resulting in the disruption of normal flow of urine [35, 36, 37, 38]. The stimulation of
4. Iron uptake systems of uropathogenic
Urinary tract has limited iron. However, UPEC are able to produce small iron chelator molecules, known as siderophores, to scavenge ferric iron (Fe3+) in the host. The most prominent ones are yersiniabactin, salmochelin, and aerobactin [48, 49]. The yersiniabactin and its receptor, FyuA, are encoded in a PAI [50, 51]. It has also been reported that for efficient biofilm formation by UPEC, FyuA is required . UPEC also secretes another important hydroxamate siderophore called aerobactin. This is produced from the condensation of two lysine and a citrate molecules. During UPEC invasion, the bacterium secretes salmochelin. Its outer membrane siderophore receptor (IroN) transports different catechol siderophores, including N-(2,3-dihydroxybenzoy)-L-serine and enterochelin also called enterobactin . Enterobactin has less solubility and stability than aerobactin [54, 55, 56] but has higher iron affinity than aerobactin in aqueous [55, 57]. UPEC also uses enterobactin for Fe3+ scavenging in the urinary tract . However, enterobactin can be inactivated by the host proteins such as serum albumin and siderocalin thereby preventing its uptake . UPEC overcomes this instability by modifying the enterobactin to salmochelin by glucosylation through the enzymatic action of glucosyltransferase and prevents it from being recognized by the host proteins . Also, UPEC has another iron acquisition system called haemin uptake system consisting of Ton-B dependent receptor (ChuA) and heavy metal associated (
5. Lipopolysaccarides of uropathogenic
Lipopolysaccharide (LPS) is a major part of the cell wall which has highly conserved lipid A-core and repeating O-antigen subunits which vary in different strains of
6. Capsule of uropathogenic
Capsule is made up of polysaccharides and it covers and protects UPEC from various harsh environmental conditions . The capsule helps UPEC to resist phagocytosis and bactericidal effects of complements in the host. It also confers antimicrobial resistance and antiserum activity to UPEC [54, 61]. Capsules like K1 and K5 interfere with the proper response of the humoral immunity of the infected host . The K1 polysaccharide plays a significant role in intracellular bacterial community (IBC) development and the pathogenesis of several UTI stages [54, 67].
7. Other virulence factors of uropathogenic
Toll receptor (TIR)/interleukin1 (IL-1) receptor domain-containing protein (TcpC) is a novel class of virulence factors that destabilize TIR signaling for UPEC to survive during UTIs . Interaction of TcpC with myeloid differentiation primary response 88 (MyD88) found in the host ends the downstream signaling pathways mediated by TLRs .
UPEC produces outer membrane protease T (OmpT) that catalyzes plasminogen activation to plasmin . OmpT helps UPEC to persist in the urinary tract when protamine and other cation peptides cleave with antibiotic activity [71, 72]. UPEC also decreases cytokines production by blocking nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) . In Table 1, prominent UPEC virulence factors, their role and genetic markers are presented.
|Virulence factor||Role||Genetic markers/gene name||References|
|Afimbrial adhesions||Binding factor||[23, 24, 54]|
|Cytotoxic necrotizing factor 1||Toxin||[38, 39]|
|Dr family of adhesions||Binding factor|||
|Haemin||Iron uptake and biofilm formation||[59, 60, 61]|
|Type 1 fimbriae||Binding factor|||
|Ferric yersiniabactin uptake receptor||Iron uptake and biofilm formation|||
|α-hemolysin||Lyses red blood cells|||
|Aerobactin||Iron chelation and uptake|||
|Outer membrane protease T||Outer membrane protease production to degrade protamine peptides||[73, 74]|
|Uropathogen specific protein||Movement of UPEC from the urinary tract to the bloodstream|||
|Class I, Class II, and Class III P-fimbriae||For binding to the uroepithelial cells||[18, 20, 21]|
|Serine-protease autotransporter toxin||Vacuolation and tissue damage||[73, 74]|
|S-fimbrial family||Binding factor||[8, 23, 24]|
Apart from possessing virulence factors, for the medical importance of