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Biomedical subjects

C A Jacobi

Publications and source records attributed to C A Jacobi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model.

BACKGROUND: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. METHODS: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. RESULTS: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.

Adenocarcinoma↗
PubMed1999

Impact of laparoscopic colonic resection on tumour growth and spread in an experimental model.

BACKGROUND: The influence of surgical manipulation and carbon dioxide pneumoperitoneum on intraperitoneal tumour growth and port-site metastasis during laparoscopic colon resection is still unknown. METHODS: Some 33 male WAG/Rij rats were randomized into three experimental groups: a laparoscopy group with carbon dioxide pneumoperitoneum (n = 11), a gasless laparoscopy group (n = 11) and a laparotomy group (n = 11). After transanal injection of a tumour cell suspension (1 x 106 CC 531 cells) into the distal colon, a colon segment resection and an end-to-end anastomosis (laparoscopy; intra-abdominal technique) were performed. Tumour growth was scored semiquantitatively 24 days after the operation. Data were analysed by the Kruskal-Wallis test. RESULTS: The tumour indices from the four locations with the greatest tumour growth were significantly decreased in the laparoscopy group with carbon dioxide pneumoperitoneum compared with the gasless laparoscopy and laparotomy groups (P < 0.01). Port-site metastases were significantly decreased in the carbon dioxide pneumoperitoneum group compared with the gasless laparoscopy group (P = 0.05). CONCLUSION: A full laparotomy incision promotes greater tumour growth than does carbon dioxide pneumoperitoneum. Surgical manipulation stimulates local tumour spread more than the establishment of a carbon dioxide pneumoperitoneum.

Animals↗
PubMed1999

Repeated boluses of local anaesthetic for pain relief after inguinal hernia repair.

OBJECTIVE: To compare the effect of repeated boluses of local anaesthetics with an oral analgesic for pain management after tension-free inguinal hernia repair. DESIGN: Prospective randomised study. SETTING: University hospital, Germany. SUBJECTS: 104 patients undergoing elective hernia repair. INTERVENTIONS: 52 patients were given boluses of 0.5% bupivacaine 10 ml through a subcutaneous catheter and 52 dipyrone 500 mg orally 6, 12 and 24 hours after operation. MAIN OUTCOME MEASURES: Postoperative pain measured on a visual analogue scale, complications, systemic side effects, supplementary analgesics, costs, and time taken to give the analgesics. RESULTS: There were no significant differences between the groups in absolute pain scores, course of pain, and the effects of analgesics. Thirteen patients [5 in the bupivacaine group and 8 in the dipyrone group] required additional dipyrone [mean (range) 2000 mg (500-5000) and 2500 mg (500-4000) respectively]. There were no systemic side effects of either treatment. There were 5 wound haematomas in the bupivacaine group (10%), and 2 wound haematomas and 1 superficial wound infection in the dipyrone group (6%). Mean costs of material and time taken to give the analgesics were pound sterling 104.70 and 47 minutes in the bupivacaine group compared with pound sterling 3.40 and 6 minutes in the dipyrone group. The median (range) hospital stay was 2 (1-3) days in both groups. CONCLUSIONS: Repeated boluses of local anaesthetic did not result in better or cheaper pain control than oral analgesics after tension-free inguinal hernia repair.

Analgesics↗
PubMed1999

Impact of laparoscopy with carbon dioxide versus helium on local and systemic inflammation in an animal model of peritonitis.

Increased intraperitoneal pressure and insufflation of carbon dioxide during laparoscopy may cause sepsis by promoting systemic inflammation in patients with intra-abdominal inflammatory diseases. The influence of carbon dioxide and helium during laparoscopy on bacteremia, endotoxemia, the plasma concentration of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha secretion ex vivo by peripheral blood mononuclear cells (PBMCs), and intraperitoneal abscess formation was investigated in an animal model. A standardized fecal inoculum was injected intraperitoneally, and rats underwent laparoscopy with either carbon dioxide (N = 20) or helium (N = 20) or no further manipulation (control group; N = 20). Bacteremia was significantly more common 1 hour after laparoscopy with CO2 than in animals receiving helium or the control group. Furthermore, helium use led to a significant decrease of bacteremia 1 week after intervention. Fecal inoculation caused significant leukocytopenia in all groups within 1 hour after intervention, with complete recovery only in the helium-treated group (p < 0.05). The TNF-alpha plasma concentration was significantly lower in the helium-treated group, and suppression of ex vivo production recovered only in the animals undergoing laparoscopy with helium (p < 0.05). The number of intraperitoneal abscesses was significantly lower after laparoscopy with helium (2+/-1.5) than after CO2 laparoscopy (6.3+/-5.1) or in the control group (5.2+/-4.8). Laparoscopy with CO2 increased systemic inflammation only slightly, while helium use was associated with a significant lower incidence of bacteremia and local and systemic inflammation compared with the control group.

Abscess↗
PubMed1999

Does dietary alpha-linolenic acid promote liver metastases in pancreatic carcinoma initiated by BOP in Syrian hamster?

BACKGROUND: alpha-Linolenic acid (ALA) has been shown to have a promoting effect on pancreatic carcinogenesis. The purpose of this study was to evaluate the influence of ALA on liver metastases in a model of BOP-induced pancreatic ductular carcinoma in the Syrian golden hamster. METHODS: While the control group (group V) received a standard diet low in fat (soya oil, 3 w/v) without ALA, groups I-IV were fed a diet high in fat (soya oil 25 w/v) with increasing percentages of ALA (2.5, 5, 7.5 and 10%) for 16 weeks. RESULTS: No significant differences in mean body weight and pancreas weight were found between the groups. But significant differences (p = 0.0001) were observed in the mean weight of the resected liver. Treatment with BOP alone resulted in the induction of well-differentiated ductal pancreatic adenocarcinoma in 91%, while all groups treated with different amounts of ALA had induction of 100%. The incidence of liver metastases differed significantly between the groups. The incidence of liver metastases in group I (2.5% ALA) was 18%, in group II (5% ALA) 27%, in group III (7.5% ALA) 50%, and in group IV (10% ALA) 91%. Moreover, the diameter of liver metastases increased significantly according to ALA supplementation (p = 0.001). CONCLUSION: The results indicate that dietary ALA increases liver metastases in BOP-initiated pancreatic cancer.

Animals↗
PubMed1999

New therapeutic strategies to avoid intra- and extraperitoneal metastases during laparoscopy: results of a tumor model in the rat.

BACKGROUND: Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. METHODS: The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1beta by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin. RESULTS: In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 +/- 153 mg) and povidone iodine (134 +/- 117 mg) compared to the control group (541 +/- 291 mg), but even less when taurolidine (79 +/- 82 mg) or taurolidine/heparin (18.3 +/- 30 mg) were instilled. CONCLUSION: Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin.

Adenocarcinoma↗
PubMed1999

[The influence of alanyl-glutamine on immunologic functions and morbidity in postoperative total parenteral nutrition. Preliminary results of a prospective randomized trial].

Glutamine seems to play an important role in metabolism and function of immunologic cells and therefore could also influence postoperative immunosuppression in surgical patients. Nevertheless, the influence of glutamine substitution in postoperative total parenteral nutrition on immunologic function and postoperative morbidity of patients is still unknown. Therefore, the impact of glutamine substitution on postoperative immunosuppression and incidence of complications was investigated in patients with surgical interventions on esophagus or stomach and total parenteral nutrition in a prospective randomized trial. To analyse the immunologic competence of the patients, the expression of CD-3, CD-4, and CD-8 on lymphocytes as well as the expression of HLA-DR and CD-14 on monocytes were evaluated before, 1, 2, 4, 7 days after surgery. Furthermore, plasma levels of IL-6 and IL-10 were analysed during the perioperative course. Actually, 34 patients have been included (with glutamine: n = 18 vs. without glutamine: n = 16) in the study. Patients with glutamine substitution showed non significantly decreased systemic inflammation (IL-6-plasma levels, leucocytosis) and significantly faster compensation of postoperative immunosuppression (HLA-DR-monocytes). Incidence of postoperative complications was decreased after glutamine substitution compared with the control group. Patients without postoperative complications showed no significant difference in postoperative immunosuppression. Although additional substitution of the amino acid glutamine might possibly decrease incidence of postoperative complications in patients with total parenteral nutrition a general advantage in postoperative immune function could not be demonstrated.

Adult↗
PubMed1998

Is tissue oxygen tension during esophagectomy a predictor of esophagogastric anastomotic healing?

PURPOSE: The genesis of anastomotic leakage and late stenosis of esophagogastrostomy is still unknown, although minimal blood flow and tissue hypoxia of the gastric tube are discussed as main reasons. However, the changes in tissue oxygen tension (PtO2) on esophagogastric anastomoses have not yet been evaluated in the perioperative course. METHODS: Submucosal tissue oxygen tension (PtO2) was measured in 33 patients with cervical esophagogastrostomy during resection of esophageal carcinoma and reconstruction by a gastric tube. Measurements were taken close to the projected resection line and latter anastomosis using a Clark-type oxygen electrode. RESULTS: Mean baseline PtO2 was 55.1 +/- 10.4 mmHg. Following the ligature of the vasa gastricae brevis and the left gastroepiploic artery (46.1 +/- 9.7 mmHg), the left gastric artery (34.8 +/- 9.8 mmHg), and the pull up of the gastric tube, PtO2 decreased to 25.8 +/- 9.4 mmHg. Anastomotic leakage occurred in 6 patients and late stenosis in 10 patients. During the operation there was no significant evidence of decreased PtO2 levels in these two groups. Postoperative PtO2 levels showed a significant increase in patients with anastomotic leakage. CONCLUSION: A disorder in oxygen consumption may cause a significant increase of PtO2 in anastomotic tissue, which is associated with anastomotic leakage.

Adult↗
PubMed1998

Increased systemic inflammation after laparotomy vs laparoscopy in an animal model of peritonitis.

OBJECTIVE: To study the influence of laparotomy and laparoscopy on local and systemic inflammation in a rat model of peritonitis. DESIGN: Bacteremia, peripheral leukocyte subpopulations, tumor necrosis factor alpha (TNF-alpha) plasma levels, and ex vivo secretion of peripheral blood mononuclear cells were investigated after laparotomy and laparoscopy in a prospective randomized experimental study. SETTING: Surgical department of a university hospital. ANIMALS: 60 male inbred Wistar rats. INTERVENTIONS: Standardized fecal inoculum was injected intraperitoneally and rats underwent laparotomy (n=20), laparoscopy (n=20), or no further manipulation (control group, n=20). Blood samples were obtained during the perioperative course to determine bacteremia, leukocytic subpopulations, TNF-alpha plasma levels, and ex vivo secretion. The number of intraperitoneal abscesses was determined in each animal after 1 week. MAIN OUTCOME MEASURE: The hypothesis of the experiment was that laparoscopy with carbon dioxide leads to an increase of local and systemic inflammation in comparison with the laparotomy and control groups. RESULTS: One hour after intervention, bacteremia was significantly higher in the laparotomy and laparoscopy groups compared with the control group (P=.01). Fecal inoculum caused significant monocytopenia and lymphocytopenia in all groups within 1 hour after intervention (P<.05), with complete recovery on day 2 only in the laparoscopy and control groups. Laparotomy caused a significant increase in TNF-alpha plasma levels and decrease of ex vivo production of TNF-alpha compared with the other 2 groups (P<.05). CONCLUSIONS: Laparotomy and laparoscopy increased the incidence of bacteremia and systemic inflammation in this peritonitis model. The inflammatory response was significantly higher in the laparotomy group compared with the laparoscopy group.

Abdominal Abscess↗
PubMed1998

Talc pleurodesis in recurrent pleural effusions.

BACKGROUND AND AIMS: The treatment of recurrent malignant pleural effusions is known to be difficult and varies from observation in asymptomatic patients to pleurectomy with varying results. This prospective study presents the efficacy and the limits of iodized talc pleurodesis in patients with malignant and non-malignant recurrent pleural effusions. METHODS: In a prospective trial talc pleurodesis was performed in 50 patients with recurrent pleural effusions (malignant effusions: n=36, non-malignant effusions: n=14). After insertion of a chest tube and complete re-expansion of the lung, 5 mg of talc and 3 mg of thymol iodine were installed with 0.5 ml of 1% xylocaine/kg body weight and 30 ml 0.9% saline solution. The chest tube was removed after an average time of 4 days and chest radiographs were performed 1 month after instillation to evaluate the efficacy of pleurodesis. RESULTS: Successful therapy was achieved in 31 of 33 patients (94%) with malignant effusions within a follow-up period of 7 months. Three patients died within 1 month after therapy due to progressive malignant disease. The treatment was successful in all cases of non-malignant effusions and complications did not occur in either group. CONCLUSIONS: These results indicate that pleurodesis with iodized talcum slurry is a simple and inexpensive method with high efficacy in controlling malignant and non-malignant pleural effusions.

Chest Tubes↗
PubMed1998

General oncologic effects of the laparoscopic surgical approach. 1997 Frankfurt international meeting of animal laparoscopic researchers.

The results from the majority of the reviewed studies support the hypothesis that abdominal surgery, performed via either a large incision or CO2 pneumoperitoneum, systemically encourages tumor growth in the postoperative period. A full laparotomy incision appears to have a significantly greater effect than CO2 pneumoperitoneum on postoperative tumor growth. Whether the large tumor observed in the surgical groups are the result of increased tumor cell proliferation or diminished tumor cell death remains unclear. There is some evidence pointing to both mechanisms. The loss of the postoperative tumor growth differences between the open and pneumo animals in the athymic mouse experiment suggests that cell-mediated immune function plays a role in tumor containment. The proliferation study results, however, suggest that other stimulatory influence(s) are also at work. Clearly, much research needs to be done regarding the etiology of these tumor growth differences. Other tumor cell lines need to be studied, and investigations regarding tumor growth in an intra-abdominal location need be performed as well. This body of research suggests that the manner in which the surgeon gains access to the abdominal cavity may have an impact on the propensity of tumor cells to implant, survive, and grow in the period immediately after surgery. If true, this may be the most compelling justification for the use of minimally invasive techniques for the curative resection of malignancies. However, it remains to be proven that human tumors will demonstrate differences in tumor growth similar to those noted in some of these animals models. Furthermore, it is not all clear that slight differences in tumor growth postoperatively will translate into significant differences in long-term survival or recurrence rates. At first glance, the existence of port-site tumors would appear to contradict totally the conclusions of many studies discussed in this synopsis. If laparoscopic methods are associated with decreased rates of tumor growth and establishment, then why do port-site tumors form? This is a complex issue calling for discussion that goes far beyond the scope of this article. However, several brief comment on this topic follow. The etiology of port tumors is unknown, although traumatization of the tumor during mobilization, resection, or removal is likely to play a significant role in the liberation of tumor cells from the primary. A relatively small protective benefit, in terms of slower tumor growth rates in laparoscopic patients, will likely not be sufficient to prevent a large inoculum of viable tumor cells in an abdominal wound from establishing a metastasis. Furthermore, as suggested earlier, the systemic effects on tumor growth may be different from the local (i.e., intra-abdominal or abdominal wound) effects. Finally, the true incidence of port tumors remains unknown. It has not been definitively established that the laparoscopic wound tumor incidence is significantly higher than the open rate, although this is the assumption of most surgeons. Several relatively large recently published laparoscopic series have reported port tumor incidences of 0 to 1.2%, which is in the same "ballpark" as the 0.6 1.0% abdominal wound tumor incidences mentioned in several open colectomy series. Clearly, much more research in this area is needed to understand port tumors better and to reconcile the port tumor results with the systemic tumor growth benefits that may be associated with minimally invasive methods.

Animals↗
PubMed1998

Prospective randomized study comparing laparoscopic and open tension-free inguinal hernia repair with Shouldice's operation.

BACKGROUND: Although tension-free techniques of hernia repair using synthetic meshes revealed encouraging results, the best method of inguinal hernia repair is still unclear. METHODS: In a prospective randomized phase-II-B study, early postoperative results of laparoscopic transabdominal preperitoneal repair (n = 80), open plug and patch repair (n = 80), and Shouldice's operation (n = 80) were compared. Postoperative pain and patient's comfort were defined as main endpoints. RESULTS: The laparoscopic approach had significantly longer operation time and was more expensive (61 +/- 12 minutes; $1,211) than plug and patch repair (36 +/- 14 minutes; $124) and Shouldice's operation (47 +/- 17 minutes; $69). Main postoperative complications were wound hematomas, seromas, and superficial wound infection, without significant difference between the groups. Postoperative pain, analgesia requirements, limitation of daily activities, and return to work did not differ between laparoscopic and open tension-free repair but were significantly lower in both groups compared with Shouldice's operation. So far, no recurrence was observed after a mean follow-up of 25 months. CONCLUSION: Open plug and patch repair is a promising technique of hernia repair in adults, because it offers the same excellent patient comfort as the laparoscopic repair but is less expensive and can be performed under local anesthesia.

Adult↗
PubMed1998

Experimental study of the effect of intra-abdominal pressure during laparoscopy on tumour growth and port site metastasis.

BACKGROUND: The influence of raised intraperitoneal pressure during laparoscopy on tumour growth and port site metastasis is still unknown. METHODS: Tumour growth of colonic adenocarcinoma DHD/K12/TRb was measured after laparoscopy with carbon dioxide at different pressures (0, 5, 10 and 15 mmHg) in a rat model. Cell kinetics were determined after incubation with carbon dioxide (0, 5, 10 and 15 mmHg) in vitro (n=60). Additionally, tumour growth was measured subcutaneously and intraperitoneally 4 weeks after laparoscopy at different intraperitoneal pressures (5, 10 and 15 mmHg) (n=100). RESULTS: In vitro tumour growth decreased significantly after incubation with carbon dioxide at 10 and 15 mmHg compared with a pressure of 0 or 5 mmHg. In vivo, mean(s.d.) intraperitoneal tumour weight was significantly increased after laparoscopy at 5 mmHg (919(1085) mg) and at 10 mmHg (1274(1523) mg) (P< 0.05), but decreased again after laparoscopy with an intraperitoneal pressure of 15 mmHg (731(929) mg) compared with the control group (365(353) mg) (P=0.3). Mean(s.d.) subcutaneous tumour growth was promoted after laparoscopy at 5 mmHg (172(234) mg), at 10 mmHg (190(253) mg) and at 15 mmHg (178(194) mg) compared with controls (48(33) mg) (P < 0.05). CONCLUSION: In vitro, raised intraperitoneal pressure leads to suppression of tumour growth. In vivo, intraperitoneal tumour growth is suppressed only by higher pressure (15 mmHg). Subcutaneous tumour growth is stimulated by carbon dioxide independently of the intraperitoneal pressure.

Adenocarcinoma↗
PubMed1998

In vitro and in vivo expression studies of yopE from Yersinia enterocolitica using the gfp reporter gene.

The Yersinia outer protein YopE belongs to the translocated effector proteins of pathogenic yersiniae. We constructed various truncated yopE genes fused to gfp (encoding the green fluorescent protein) to study yopE gene expression and YopE-GFP translocation of Y. enterocolitica in cell culture and mouse infection models. The hybrid gene fusions were co-expressed in Y. enterocolitica (i) on a low-copy plasmid in the presence of the virulence plasmid pYV08 (in trans configuration) and (ii) after co-integration by homologous recombination of a yopE-gfp-carrying suicide plasmid into pYV08 (co-integrate configuration). After 30min of infection of HEp-2 cell monolayers, extracellularly located yersiniae began to emit green fluorescence after excitation. In contrast, internalized bacteria were weakly fluorescent. Translocation of YopE-GFP into HEp-2 cells by attached yersiniae was visualized by optical sectioning of fluorescent HEp-2 cells using confocal laser scanning microscopy and was confirmed by immunoprecipitation of cytosolic YopE-GFP from selectively solubilized HEp-2 cells. The co-translocation of other Yops was not significantly impaired by YopE-GFP as shown by YopH/YopE-mediated suppression of the oxidative burst of infected neutrophils. The time course of yopE-gfp expression (in trans as well as in the co-integrate configuration) in the HEp-2 cell infection model as well as after in vitro induction was studied using a highly sensitive CCD camera and a flow cytometer. Similar results were obtained with a YopE-LUC (firefly luciferase) protein fusion as reporter. After intraperitoneal, intravenous and orogastrical infection of Balb/c mice with the recombinant yersiniae strains, green fluorescing bacteria could be visualized microscopically in the peritoneum, the spleen, the liver and in the Peyer's patches. However, only weakly fluorescent yersiniae were observed in the intestinal lumen. These results were quantified by flow cytometric measurements. The application of gfp as a reporter gene turned out to be promising for the study of protein translocation by protein type III secretion systems and differential virulence gene expression in vivo.

Animals↗
PubMed1998

The yersiniabactin biosynthetic gene cluster of Yersinia enterocolitica: organization and siderophore-dependent regulation.

The ability to synthesize and uptake the Yersinia siderophore yersiniabactin is a hallmark of the highly pathogenic, mouse-lethal species Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica 1B. We have identified four genes, irp1, irp3, irp4, and irp5, on a 13-kb chromosomal DNA fragment of Y. enterocolitica 08, WA-314. These genes constitute the yersiniabactin biosynthetic gene cluster together with the previously defined irp2. The irp1 gene consists of 9,486 bp capable of encoding a 3,161-amino-acid high-molecular-weight protein 1 (HMWP1) polypeptide with a predicted mass of 384.6 kDa. The first 3,000 bp of irp1 show similarity to the corresponding regions of the polyketide synthase genes of Bacillus subtilis and Streptomyces antibioticus. The remaining part of irp1 is most similar to irp2, encoding HMWP2, which might be the reason for immunological cross-reactivity of the two polypeptides. Irp4 was found to have 41.7% similarity to thioesterase-like protein of the anguibactin biosynthetic genes of Vibrio anguillarum. Irp5 shows 41% similarity to EntE, the 2,3-dihydroxybenzoic acid-activating enzyme utilized in enterobactin synthesis of Escherichia coli. Irp4 and Irp5 are nearly identical to YbtT and YbtE, recently identified in Y. pestis. irp3 has no similarity to any known gene. Inactivation of either irp1 or irp2 abrogates yersiniabactin synthesis. Mutations in irp1 or fyuA (encoding yersiniabactin/pesticin receptor) result in downregulation of irp2 that can be upregulated by the addition of yersiniabactin. A FyuA-green fluorescent protein translational fusion was downregulated in an irp1 mutant. Upregulation was achieved by addition of yersiniabactin but not desferal, pesticin, or pyochelin, which indicates high specificity of the FyuA receptor and autoregulation of genes involved in synthesis and uptake of yersiniabactin.

Amino Acid Sequence↗