Active immunization with LD842, a plasmid-cured strain of Salmonella dublin, protects mice against group D and group B Salmonella infection.
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Animals↗
Biomedical subjects
J Fierer
Publications and source records attributed to J Fierer.
Physical and genetic mapping of the Salmonella dublin virulence plasmid pSDL2. Relationship to plasmids from other Salmonella strains.
Plasmids of approximately 80 kb in size are found in nearly all clinical isolates of Salmonella dublin and are believed to be essential for virulence. We have shown previously that the 80-kb plasmid pSDL2 is required for the S. dublin Lane strain to establish a lethal systemic infection in BALB/c mice after oral or intraperitoneal inoculation. We now present a physical and genetic characterization of pSDL2. We have established a complete restriction endonuclease cleavage map of pSDL2 for five enzymes: Xba I, Bam HI, Xho I, Sal I, and Hind III. The region specifying autonomous replication has been localized to a 10.5-kb region of the Sal I A fragment by subcloning on the vector pBR322. Using transposon insertion mutagenesis with Tn5-oriT, a region encoding the virulence phenotype has been mapped within a 6.4-kb portion of the Sal I B fragment. Deletions generated by partial Eco RI restriction digestion demonstrate that at least 50 kb of the plasmid DNA are not required for replication or virulence functions, confirming the map location of these phenotypes. Plasmids of different sizes and restriction patterns were found in mouse virulent strains of S. dublin Vi+, S. enteritidis, and S. choleraesuis. By Southern hybridization, these putative virulence plasmids share a common 4-kb Eco RI fragment with the virulence region of pSDL2, and the plasmids from S. dublin Vi+ and S. enteritidis were shown to express mouse virulence comparable to pSDL2.
Cloning, Molecular↗
Natural history of oral Salmonella dublin infection in BALB/c mice: effect of an 80-kilobase-pair plasmid on virulence.
BALB/c mice were infected orally with Salmonella dublin strains Lane and LD842, an isogenic derivative of the former that is avirulent because it was cured of its 80-kilobase-pair virulence plasmid pSDL2. Both strains colonized the intestine and invaded Peyer's patches with equivalent efficiency. However, the parent strain multiplied in mesenteric nodes and in the spleen; the plasmid-cured strain reached these organs, but the infection was low grade and remained relatively static until the mice developed active immunity and cured themselves. The histological response to plasmid-free strain LD842 was mononuclear, whereas the virulent parent strain produced abscesses. Sublethal irradiation of the mice before infection with strain LD842 prevented the mononuclear infiltrate in the liver and made the animals susceptible. Thus the virulence plasmid of S. dublin allows multiplication within the reticuloendothelial system and does not have any effect on the organism's ability to colonize the intestine or invade Peyer's patches.
Animals↗
Non-pulmonary Rhodococcus equi infections in patients with acquired immune deficiency syndrome (AIDS).
Rhodococcus equi, formerly known as Corynebacterium equi, was isolated repeatedly from the blood of two patients with the acquired immune deficiency syndrome (AIDS). Neither of the patients had pneumonia while they were bacteraemic, whereas pneumonia has been present in all previously reported cases of human infection with R equi. One of our patients had diarrhoea and the organism was isolated from a stool culture; the other patient had a large granulomatous soft tissue mass in his pelvis caused by R equi. Both isolates were resistant to penicillin and one produced a beta-lactamase. Both patients were treated with vancomycin but only one recovered.
Acquired Immunodeficiency Syndrome↗
Acute pyelonephritis.
Microbial factors that contribute to the virulence of uropathogens, and host factors that predispose to urinary tract infection are summarized in this article. The limitations of methods used to differentiate between upper and lower urinary tract infections are discussed. Recommendations for the treatment of pyelonephritis and its complications are outlined, with an emphasis on the use of safe, potent, renally excreted antimicrobials.
Acute Disease↗
Streptococcus sanguis II (viridans) prosthetic valve endocarditis with myocardial, splenic and cerebral abscesses.
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Abscess↗
Influence of vegetation size on clinical outcome of right-sided infective endocarditis.
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Endocarditis, Bacterial↗
Intraosseous and intradiscal gas in association with spinal infection: report of three cases.
The detection of a vacuum phenomenon within the intervertebral disk usually confirms the diagnosis of degenerative disease rather than an infective process. A similar phenomenon in the vertebral body generally indicates ischemic necrosis. However, spinal infection may rarely be accompanied by intradiscal or intraosseous gas so that the latter finding does not entirely exclude the possibility of infection. Three cases are reported to illustrate gas formation in association with vertebral infection.
Escherichia coli Infections↗
Infections and infection risk in residents of long-term care facilities: a review of the literature, 1970-1984.
We reviewed the English-language peer-reviewed journals and the Centers for Disease Control's Morbidity and Mortality Weekly Reports between 1970 and 1984 presenting information about infections and infection risk in residents of long-term care facilities. More than 50 articles met review criteria. Approximately one third of the articles were reports of outbreaks, primarily of respiratory and gastrointestinal infections. Seven articles reported rates for several infection sites, but most rates were not directly comparable to one another because numerators and/or denominators were different. Many of the studies have been done in Veterans Administration hospitals with largely male populations, which may limit their applicability to freestanding long-term care facilities with largely female clients. This review establishes the need for high-quality observational studies of infections in long-term care facilities. Such studies are needed before intervention studies can be done to measure the effect of manipulation of risk factors on infection outcome.
Aged↗
D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice.
Two strains of mice (C57BL/10ScN and C3H/HeJ) that carry the same mutant lipopolysaccharide gene (Lpsd) which makes them resistant to the toxic effects of endotoxin (LPS) are also partially resistant to the hepatotoxic effects of D-galactosamine. As measured by serum alanine aminotransferase, the degree of liver injury induced by D-galactosamine in the LPS-resistant strains is only 10%-30% that of closely related strains of LPS-sensitive mice. Similarly, histopathologic changes are less pronounced in the endotoxin-resistant strains than in LPS-susceptible mice. By transferring spleen cells from LPS-susceptible strains to lethally irradiated, LPS-resistant mice, we established that susceptibility to D-galactosamine is mediated by lymphoreticular cells. Radiation-resistant spleen cells transferred D-galactosamine sensitivity, suggesting a role for macrophages. We did not exclude the possibility that lymphocytes can also transfer the response to D-galactosamine. These results establish that in mice, D-galactosamine sensitivity is associated with endotoxin sensitivity and that the former is mediated by lymphoreticular cells, not by hepatocytes.
Animals↗
Plantar compartmental infection in the diabetic foot. The role of computed tomography.
This review discusses the role of computed tomography (CT) in the evaluation of extent of plantar soft tissue infection in the diabetic foot. CT abnormalities are correlated with conventional radiography, results of preoperative aspiration cultures, intraoperative assessment, and bone, gallium, and 111In-leukocyte scan findings. Plantar soft tissue disease respects compartmental boundaries in general, with transcompartmental spread possible along musculotendinous units that normally transgress the intervening fascial septae. CT correlates well with the extent of infection as determined by other modalities, but cannot precisely predict its proximal boundary due to gradual transition between unequivocally abnormal and normal tissue. CT may be useful in establishing an appropriate level for contemplated amputation and can detect extension of superficial diabetic foot infections at an earlier stage than existing clinical methods, potentially resulting in less extensive surgical procedures.
Bacterial Infections↗
Plasmid-mediated virulence in Salmonella dublin demonstrated by use of a Tn5-oriT construct.
Salmonella dublin, a serotype which causes invasive disease in cattle and humans, carries a characteristic 80-kilobase plasmid (pSDL2). We were able to cure the plasmid from a strain of S. dublin. The cured strain was avirulent for mice by either the oral or intraperitoneal route of infection. A derivative of Tn5 which contains the transfer origin of the broad-host-range plasmid RK2 (Tn5-oriT) was transposed onto pSDL2, allowing mobilization of the plasmid by an RK2 helper plasmid. Reintroduction of the pSDL2 derivative plasmid into the cured strain restored virulence, demonstrating that the plasmid is necessary for virulence. These studies also demonstrate the usefulness of the Tn5-oriT construct for genetic manipulations.
Animals↗
Chronic osteomyelitis: monitoring by 99mTc phosphate and 67Ga citrate imaging.
Thirteen patients with chronic osteomyelitis, treated for 6 months with rifampin, had serial 99mTc phosphate and 67Ga scans to determine their value in assessing response to treatment. In patients who responded to treatment, gallium scans were deemed more accurate than 99mTc phosphate bone scans. The gallium scans, although still abnormal at the end of 6 months of antibiotic therapy, showed an improvement trend in all the responders except one in whom fracture recurred. Worsening or lack of improvement on gallium scans predicted active bone infection in five of six "clinical-failure" patients who had documented active bone infection. 67Ga scans eventually became normal in all patients who remained asymptomatic (excluding one with recurrent fracture). 99mTc phosphate scans became normal in only one of five clinical responders. All nonresponders had persistently abnormal scans, although after 6 months of therapy only four of seven showed worsening or no improvement on the scan. Therefore, 67Ga is preferred over 99mTc phosphate bone scans in the assessment of response to therapy in chronic bone infection. Clinical utility of the gallium scan is most significant in patients whose clinical assessment is uncertain, but routine use of this technique does not appear to be warranted. Gallium images are most valuable when obtained over a period of time, so that the trend of improvement versus nonimprovement is evident.
Chronic Disease↗
Genetic control of resistance to Coccidioides immitis: a single gene that is expressed in spleen cells determines resistance.
We have previously reported that inbred mice vary widely in their resistance to Coccidioides immitis peritonitis. To investigate the number of genes controlling resistance, (susceptible X resistant)F1 X susceptible backcross mice were tested for resistance to infection. A 1:1 ratio of resistant:susceptible offspring was observed, which is consistent with a single dominant gene determining resistance. To find out whether this gene, which we designated Cms, is expressed in the immune and/or the inflammatory responses, radiation chimeras were constructed by transplanting spleen cells from the resistant F1 mice into the susceptible parental strain. These chimeras were consistently more resistant to infection than the susceptible parental strain. We concluded that resistance to C. immitis is determined primarily by a single gene, and that this gene is expressed by spleen cells.
Animals↗
African trypanosomiasis alters prostaglandin production by murine peritoneal macrophages.
Many factors contribute to the severe immunosuppression associated with African trypanosomiasis. Macrophages have been shown to be important target cells which after uptake of parasites, mediate immune dysfunction in vivo. We observed that infection of mice with Trypanosome brucei brucei (clone NIM 6) induces profound changes in arachidonic acid metabolism and prostaglandin (PG) secretion by macrophages. Normal macrophages release more PGI2 than PGE2 and production of both these prostaglandins is stimulated equally by endotoxin (LPS). Macrophages taken from NIM 6 infected mice at the peak of the first parasitaemia, release increased amounts of PGE2 and are hyperresponsive to LPS stimulation, while PGI2 secretion remains normal. As the infection progresses, there is a striking decrease in both basal PGE2 and PGI2 secretion and the ability of macrophages to respond to LPS. By the third week of infection, shortly before death, peritoneal macrophages resemble thioglycollate elicited macrophages in their inability to be stimulated by LPS to synthesize prostaglandins. Infection with a more virulent clone of T. brucei (NIM9) results in suppression of both PGE2 and PGI2 release by day 9 of infection. The increased production of PGE2 by macrophages during the height of infection is likely to contribute to the general immunosuppression associated with African trypanosomiasis.
Animals↗
Cyclosporin A inhibits Coccidioides immitis in vitro and in vivo.
BALB/c mice infected intraperitoneally with Coccidioides immitis were treated with cyclosporin (CyA) subcutaneously. CyA prevented infection when treatment was started at day zero. When treatment was delayed until day 6 after infection, the mice that received either 75 or 25 mg/kg per day survived, but those treated with 7.5 mg/kg per day had the same mortality rate as controls. The higher doses of CyA prevented dissemination of the fungus from the peritoneum to the lung but did not eliminate the peritoneal infection. In vitro, CyA inhibited the growth of the mycelial phase of eight test strains of C. immitis at a concentration of 1.0 microgram/ml. One or two strains of 10 other fungi were tested for susceptibility to CyA; only Aspergillus niger was inhibited, at a concentration of 0.1 microgram/ml. CyA is structurally unrelated to the polyenes and imidazoles and has a very restricted spectrum of antifungal activity. CyA may represent a new class of antifungal agents with a novel mechanism of antifungal activity.
Animals↗
Inbred mouse strains differ in resistance to lethal Coccidioides immitis infection.
Inbred strains of mice were infected intraperitoneally with Coccidioides immitis, and the mean lethal dose was determined after 28 days. DBA/2N mice had a mean lethal dose of greater than 10(5) arthroconidia, whereas BALB/cAnN, C57BL/6N, and C57L/J mice had a mean lethal dose of less than or equal to 10(3). Since both BALB/c and DBA/2 mice are the H-2d haplotype, resistance is not primarily determined by the major histocompatibility locus. Resistance was the dominant phenotype. The pattern of C. immitis-resistant strains does not correspond to the strain distribution of the lsh gene or to the pattern of resistance to Blastomyces dermatitidis or Cryptococcus neoformans. Both resistant and susceptible mice, however, could be successfully immunized with a killed spherule vaccine, and susceptible BALB/cAnN mice were protected from an otherwise lethal infection by prior immunization with an attenuated mutant of C. immitis. Despite the evidence that BALB/cAnN mice could respond to immunization, nonimmune mice did not control the later phase of intraabdominal infection as well as DBA/2N mice. Dissemination of C. immitis to the lung occurred frequently in BALB/cAnN but not in DBA/2N mice. This suggests that BALB/cAnN mice cannot mount an effective immune response to C. immitis during the course of infection.
Animals↗
Distinctive biochemical features of Salmonella dublin isolated in California.
We examined 34 strains of Salmonella dublin that were isolated in California between 1978 and 1982. All were of a characteristic biotype; they did not grow on Simmons citrate or acetate and did not ferment arabinose. Their apparent inability to use citrate as the only carbon source was due to a nutritional requirement for nicotinic acid. Because S. dublin strains are of a characteristic biotype, are host adapted to bovines, and are unusually virulent for humans, we suggest that S. dublin be considered a separate species of the genus Salmonella. It is important that clinical laboratories recognize and differentiate this organism from less pathogenic salmonellae so that they can alert clinicians to the presence of this invasive microorganism.
Animals↗