Abstract
The uropathogenic Escherichia coli 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 E. coli 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 tcpC gene stopped replication of CFT073. Overexpression of several tcpC-truncation constructs revealed a transmembrane region, while its TIR domain induced filamentous bacteria. Based on these observations, we hypothesized that tcpC 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 tcpC 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 FeSO4 concentrations suppressed their activity. Human urine activated P2, demonstrating that tcpC might be induced in the urinary tract of infected patients. We conclude that P2, consisting of a 240 bp region 5′ of the tcpC gene, represents the major regulator of tcpC expression.
Highlights
Urinary tract infections are frequent, often recurrent and most often caused by uropathogenic Escherichia coli (UPEC)
Growth of CFT073 was impaired when the tcpC gene was induced at the beginning of the culture and it stopped when the gene was induced after the culture reached an OD600 density of 0.5 (Figure 1C)
Our results demonstrate that overexpression of Toll/ interleukin-1 receptor domain-containing protein C (TcpC) influences the UPEC strain the results of three independent experiments
Summary
Urinary tract infections are frequent, often recurrent and most often caused by uropathogenic Escherichia coli (UPEC). Expanding antibiotic resistance hampers successful treatment of urinary tract infections with UPECs. exploration of the hostpathogen interaction is crucial for the elucidation of new treatment mechanisms and approaches. We detected a new class of virulence factors in the uropathogenic E. coli strain. CFT073 and in Brucella spp., which impair Toll-like receptor (TLR) signaling [1]. Other groups detected structurally similar virulence factors with almost identical mechanisms in human pathogens such as Salmonella enterica subsp. Enterica Serovars Enteritidis, Dublin, Gallinarum, Yersinia spp., Brucella spp., Staphylococous aureus MSSA476, Enterococcus faecalis, and in non-pathogens such as Paracoccus denitrificans [3,4,5,6,7,8,9,10,11]. At least some of these TLR-inhibiting virulence factors significantly increase disease severity in different murine infection models [1,3,4,6,12]
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