**6. Lipopolysaccharide**

**4.2. Enterobactin**

**4.3. Yersiniabactin**

**4.4. Salmochelin**

**4.5. Hemin uptake system**

mum kidney colonization [51].

**5. Capsule**

Enterobactin is another specialized highly prevalent catecholate siderophore which is less soluble and less stable than aerobactin [53–55]. But this siderophore has a higher iron affinity and can deferrate transferrin more rapidly than aerobactin in aqueous solution [13, 54]. However, iron is released from enterobactin through the hydrolysis of this siderophore [13]. Besides these, enterobactin may afford UPEC the ability to colonize within an iron-limiting environment such as the urinary tract [56]. But this siderophore has a limitation that it can be

Yersiniabactin, a mixed-type siderophore, is widespread in *Enterobacteriaceae* including *E. coli* and encoded on the high-pathogenicity island [53]. Yersiniabactin has a high iron affinity and produced yersiniabactin-Fe3+ complex binding to the iron molecule which recognizes the specific bacterial outer membrane TonB-dependent receptor and Fyu (Psn). The iron molecule is released from yersiniabactin in the cytosol with the help of membrane-embedded proteins [57]. In addition, this siderophore increases resistance to copper stress by chelating Cu2+ [10].

Salmochelin is a glucosylated derivative of enterobactin which is not recognized by siderocalin and thus escapes from the host immune response [53]. However, siderocalin, neutrophil gelatinase-associated lipocalin is also known as lipocalin 2 that binds enterobactin and prevents its uptake [53, 56]. To overcome this, enterobactin is modified to salmochelin by glucosylation via the action of glucosyltransferase and is not recognized by lipocalin 2 [56]. However, a recent study found that salmochelin siderophore receptor IroN is involved in the invasion of urothelial cells, and thus IroN may play both an iron uptake receptor and an

There is another iron acquisition system called hemin uptake system including ChuA and Hma, which involves direct upregulation of haem receptors. This system uptakes free iron during UTIs, and several studies found its role in bacterial growth and biofilm formation [48, 58, 59]. ChuA expression is regulated by other regulatory proteins, for instance, in uropathogenic *E. coli* strain 536, increase in RfaH level induces the expression of ChuA [60]. But the other receptor Hma functions independently of ChuA, and a residue, Tyr-126, is necessary for its function. However, both ChuA and Hma contribute to haem utilization which is required for the maxi-

The main role of a capsule is to cover and protect the bacterium from various unfavorable conditions as well as the host immune system, which is mainly constituted of polysaccharide [1].

inactivated by host proteins such as serum albumin and siderocalin [25].

14 Microbiology of Urinary Tract Infections - Microbial Agents and Predisposing Factors

internalization factor in the establishment of urinary tract infections [26].

Lipopolysaccharide (LPS) is an integral component of the cell wall and consists of the highly conserved lipid A-core and repeating O-antigen subunits that differ greatly between strains based on the sugar residues and their linkage patterns within the repeating subunits [37, 61]. LPS is very well known to activate host response and to induce nitric oxide and cytokine (IL-1, TNF-α) production which enhances the inflammatory response [1, 15]. It also induces the synthesis of specific antibodies to the somatic antigen and exerts an immune-adjuvant effect that promotes the humoral immune response to other antigens of the pathogen. However, certain antigenic types of LPS are also involved in resistance of the pathogen to the killing effect of the normal human serum [46]. According to study upon animal models, acute renal failure due to LPS depends on the systemic response to LPS and does not depend on expression of functional LPS receptor, TLR4, in the kidney. But it is not clear whether LPS plays a role in mediating a renal failure and acute allograft injury in patients with ascending UTIs [1].
