| Summary: | The uropathogenic <i>Escherichia coli</i> strain CFT073 causes kidney abscesses in mice Toll/interleukin-1 receptor domain-containing protein C (TcpC) dependently and the corresponding gene is present in around 40% of <i>E. coli</i> isolates of pyelonephritis patients. It impairs the Toll-like receptor (TLR) signaling chain and the NACHT leucin-rich repeat PYD protein 3 inflammasome (NLRP3) by binding to TLR4 and myeloid differentiation factor 88 as well as to NLRP3 and caspase-1, respectively. Overexpression of the <i>tcpC</i> gene stopped replication of CFT073. Overexpression of several <i>tcpC</i>-truncation constructs revealed a transmembrane region, while its TIR domain induced filamentous bacteria. Based on these observations, we hypothesized that <i>tcpC</i> expression is presumably tightly controlled. We tested two putative promoters designated P1 and P2 located at 5′ of the gene c2397 and 5′ of the <i>tcpC</i> gene (c2398), respectively, which may form an operon. High pH and increasing glucose concentrations stimulated a P2 reporter construct that was considerably stronger than a P1 reporter construct, while increasing FeSO<sub>4</sub> concentrations suppressed their activity. Human urine activated P2, demonstrating that <i>tcpC</i> might be induced in the urinary tract of infected patients. We conclude that P2, consisting of a 240 bp region 5′ of the <i>tcpC</i> gene, represents the major regulator of <i>tcpC</i> expression.
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