Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili.
Uropathogenic Escherichia coli, the predominant causative agent of urinary tract infections, use type 1 pili to bind and invade bladder epithelial cells. Upon entry, the bacteria rapidly replicate and enter a complex developmental pathway ultimately forming intracellular bacterial communities (IBCs), a niche with biofilm-like properties protected from innate defences and antibiotics. Paradoxically, bacteria within IBCs produce type 1 pili, an organelle thought only to be an extracellular colonization factor. Thus, we investigated the function of type 1 pili in IBC development. The cystitis isolate, UTI89, was genetically manipulated for conditional fim expression under control of the tet promoter. In this strain, UTI89-tetR/P(tet) fim, piliation is constitutively inhibited by the tetracycline repressor, TetR. Repression is relieved by anhydrotetracycline (AHT) treatment. UTI89-tetR/P(tet) fim and the isogenic control strain, UTI89-tetR, grown in the presence of AHT, colonized the bladder and invaded the superficial umbrella cells at similar levels at early times in a murine model of infection. However, after invasion UTI89-tetR/P(tet) fim became non-piliated and was unable to form typical IBCs comprised of tightly packed, coccoid-shaped bacteria in contrast to the control strain, UTI89-tetR. Thus, this work changes the extracellular colonization functional paradigm of pili by demonstrating their intracellular role in biofilm formation.
Wright
Kelly J
KJ
Department of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Seed
Patrick C
PC
Hultgren
Scott J
SJ
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000378:metabolism*; D005260:Female; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006168:Guinea Pigs; D006384:Hemagglutination; D051379:Mice; D008809:Mice, Inbred C3H; D014552:Urinary Tract Infections / Q000378:metabolism / Q000382:microbiology; D019459:Urothelium / Q000166:cytology / Q000378:metabolism / Q000382:microbiology