Yersinia enterocolitica Infection of Mice Reveals Clonal Invasion and Abscess Formation

Abstract

Yersinia enterocolitica is a common cause of food-borne gastrointestinal disease leading to self-limiting diarrhea and mesenteric lymphadenitis. Occasionally, focal abscess formation in the livers and spleens of certain predisposed patients (those with iron overload states such as hemochromatosis) is observed. In the mouse oral infection model, yersiniae produce a similar disease involving the replication of yersiniae in the small intestine, the invasion of Peyer's patches, and dissemination to the liver and spleen. In these tissues and organs, yersiniae are known to replicate predominately extracellularly and to form microcolonies. By infecting mice orally with a mixture of equal amounts of green-and red-fluorescing yersiniae (yersiniae expressing green or red fluorescent protein), we were able to show for the first time that yersiniae produce exclusively monoclonal microcolonies in Peyer's patches, the liver, and the spleen, indicating that a single bacterium is sufficient to induce microcolony and microabscess formation in vivo. Furthermore, we present evidence for the clonal invasion of Peyer's patches from the small intestine. The finding that only very few yersiniae are required to establish microcolonies in Peyer's patches is due to both Yersinia-specific and host-specific factors. We demonstrate that yersiniae growing in the small intestinal lumen show strongly reduced levels of invasin, the most important factor for the early invasion of Peyer's patches. Furthermore, we show that the host severely restricts sequential microcolony formation in previously infected Peyer's patches.

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

“…The resulting strains WA-TTSS-YopE and WA-TTSS-YopP produce YopE or YopP, respectively, but no other effector Yops. To localize yersiniae in cells expressing GFP-LC3 the Yersinia strains WA, WA-C, WA-C-⌬inv, and WA-⌬lcrD were transfected with plasmid pLAC-RFP which constitutively labels the bacteria with RFP (41). Additionally, we investigated cellular effects induced by the E. coli strain HB101-pINV1914 expressing the Y. enterocolica inv gene (E. coli-invϩ) and by its invasin-negative parent E. coli laboratory strain HB101 (42).…”

Susceptibility to Yersinia pseudotuberculosis Infection is Linked to the Pattern of Macrophage Activation

“…In the mouse oral infection model, enteropathogenic yersiniae produce systemic disease, the bacteria replicating in the small intestine, invading the Peyer's patches and disseminating to the liver and spleen [2,3].…”

Yersinia enterocolitica YopH-Deficient Strain Activates Neutrophil Recruitment to Peyer's Patches and Promotes Clearance of the Virulent Strain

“…Control mice received PBS. In coinfection experiments, Y. enterocolitica ⌬yopH was administered in combination with Y. enterocolitica WT or with Y. enterocolitica WT-green fluorescent protein (GFP) (24) with an equal dose of 2.5 ϫ 10 8 or 1 ϫ 10 10 CFU, respectively. The number of inoculated bacteria was controlled by plating of serial dilutions of the inoculated suspension on Trypticase soy agar (TSA) and determining the CFU after incubation at 27°C for 48 h. To determine the bacterial burden after infection, spleen, PP, and feces were obtained and homogenates were prepared in isotonic saline solution or in a cold extraction buffer (50 mM EDTA, 30 mg/ml soybean trypsin inhibitor, 1% bovine serum albumin in PBS) for feces.…”