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Biomedical subjects

C Svanborg Edén

Publications and source records attributed to C Svanborg Edén.

At least 19 recordsLinked to original sources

Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion.

Why do parasites kill their hosts? During this past decade, research in three different areas; evolutionary ecology, medical microbiology, and population genetics has provided theory and data that address this and related questions of selection and the evolution and maintenance of parasite virulence. A general theory of parasite-host coevolution and the conditions for selection to favour parasite virulence has been put forth. Considerable advances have been made in elucidating the mechanisms of pathogenicity and inheritance of virulence in bacteria. The population genetic structure and the relationship between pathogenic and non-pathogenic forms has been determined for a number of species of bacteria. We critically review these developments and their implications for questions of selection and the evolution and maintenance of virulence in bacteria. We postulate how selection may operate on specific types of bacterial virulence and present a general protocol to experimentally test hypotheses concerning selection and the evolution of virulence in bacteria.

Animals

Frequency and organization of pap homologous DNA in relation to clinical origin of uropathogenic Escherichia coli.

The pap operon encodes the gal alpha 1-4gal beta specific adhesins of Escherichia coli. The presence and organization of pap homologous DNA was determined using two probes specific for pap in 217 uropathogenic E. coli samples by dot blot and Southern blot analysis. The frequency of pap homologous DNA was 76% in pyelonephritis, 69% in cystitis, and 52% in an asymptomatic bacteriuria group. Further, the gal alpha 1-4gal beta binding phenotype among the pap-positive strains was expressed more often in acute pyelonephritis (91%) than the cystitis (60%) or asymptomatic bacteriuria (52%) strains. This was explained in part by difference in organization of pap homologous DNA between the genotypically positive pyelonephritis and asymptomatic bacteriuria strains. The pyelonephritis isolates contained three copies of pap significantly more often than the asymptomatic bacteriuria strains, and the pyelonephritogenic O-antigen types had a general increase in pap copy number. The difference in expression of gal alpha 1-4gal beta adhesins between pyelonephritis and asymptomatic bacteriuria isolates was thus not only a function of the frequency of pap homologous DNA but also of phenotypic expression among genotypically pap-positive strains.

Acute Disease

Outbreak of Haemophilus influenzae type b meningitis in a day care center.

Three cases of Haemophilus influenzae type b (Hib) meningitis in a Swedish day care center prompted the investigation of the nasopharyngeal carriage in attendees of that day care center (I), and among children in another day center (II) in the same city, but without meningitis cases. Because the evaluation of the spread of Haemophilus influenzae (Hi) isolates through a population, such as children in day care centers, requires stable identification markers for the bacteria, this study used multilocus enzyme electrophoresis to separate Hib carried by day care attendees from the disease-associated Hib clone. The three meningitis episodes were caused by the same clone of Hib (ET14). This and other Hib clones occurred in the healthy carriers. The frequency of H. influenzae carriage and composition of the H. influenzae flora differed between the two day care centers. Center I with the meningitis cases had a lower overall frequency of H. influenzae carriage, 11 of 40 (28%) compared with both the control day care center (57%) and previous studies. The main difference between the two day care centers was in the nontypable H. influenzae (HiNT) flora. The frequency of HiNT was higher in the center without Hib disease, and there was a higher degree of sharing of HiNT isolates among the children in Center II. This raised the question of an inverse relationship between carriage of HiNT and Hib infection. The results emphasized the importance of accurate identification of the disease isolate in order to estimate the risk of acquisition and dissemination to secondary cases.

Carrier State

Ciclosporin-dependent, nu-independent, mucosal interleukin 6 response to gram-negative bacteria.

Regulation of the mucosal inflammatory response to Gram-negative bacteria was analysed. The interleukin 6 (IL-6) secretion, influx of polymorphonuclear leucocytes into urine, and bacterial clearance from the kidneys were compared between Balb/c (nu/nu) and nu/+/- mice, with and without ciclosporin (CsA) treatment. There was no significant influence of the nu genotype on any of the host responses measured. CsA pretreatment significantly decreased Il-6 secretion in both nu/nu and nu/+/- mice, but did not affect bacterial clearance or the leucocyte response in any mouse strain tested. Tissue damage, in addition to bacterial infection, resulted in significantly higher levels of IL-6 than bacterial infection alone. Tissue-damaged mice were significantly less likely to clear the bacterial infection than their non-damaged counterparts, but there was no significant difference in the leucocyte response. CsA pretreatment did not significantly reduce the levels of IL-6 in the tissue-damaged mice. These results demonstrate that the mucosal inflammatory response to Gram-negative infection, including IL-6 secretion, is nu-independent, and that bacterial infection alone or in combination with tissue damage induce IL-6 secretion by two different pathways.

Animals

Assessment of biological and colony hybridization assays for detection of the aerobactin system in Escherichia coli from urinary tract infections.

A total of 466 E. coli strains from urinary tract infections (UTI) were screened for the presence and expression of the aerobactin system by a colony hybridization test and a bioassay. A probe carrying part of the genes for aerobactin synthesis was used. A total of 43.1% (201) of the strains were positive in the probe test and undoubtedly positive in the bioassay. When doubtfully positive bioassays were included, this figure rose to 49.8% (232). An additional 4.9% (23) of the strains were positive in the colony hybridization test only while 44% (205) of the strains were negative in both tests. Doubtfully positive bioassays were probably due either to a false positive reaction or to a weak expression of the aerobactin system. 01:K1:H- strains were characteristically probe positive and doubtfully positive in the bioassay. The incidence of isolates positive by both methods or by only one of them was significantly higher among isolates from cases of pyelonephritis (Py) than among those from asymptomatic bacteriuria (ABU) and normal feces (FN) (P less than 0.01).

2,2'-Dipyridyl

Special virulence of the Escherichia coli O1:K1:H7 clone in acute pyelonephritis.

The relationship between acute-phase responses and bacterial properties was studied in a population of 88 children with their first known episode of acute pyelonephritis. One strain from each patient was included in the study. Eighty-four of the patients were infected with Escherichia coli, which was assigned a clonotype according to the O:K:H stereotype; 55 patients carried one of the 12 multiply occurring clones. Globotetraosylceramide-specific (globo+) adhesion was present in 90% of these 12 clones, compared with 62% in the remaining 29 singly occurring clones. The patients infected with globo+ strains had significantly increased inflammatory reactions compared with patients with globo- strains. The O1:K1:H7 strain was the single most frequent clone (n = 14) that always expressed globo+ adhesins. Patients infected with O1:K1:H7 had an inflammatory response similar to that of other globo+ infections, but had a shorter duration of symptoms before diagnosis, higher fever, and higher peripheral leukocyte count. These results demonstrate special virulence of the O1:K1:H7 clone, reflected by the acuteness of onset of infection.

Child

Bacterial attachment as a predictor of renal abnormalities in boys with urinary tract infection.

The development of renal scarring was analyzed prospectively in 241 boys with their first known episode of symptomatic urinary tract infection (140 acute pyelonephritis, 61 acute cystitis, and 40 nonspecific). Of 197 boys undergoing urography, 22 (11%) had scars; 20 were in the pyelonephritis group. Vesicoureteral reflux occurred in 81% of those with scarring, compared with 20% of those without scarring. The bacteria causing the first episode of urinary tract infection in each patient were saved, and Escherichia coli organisms were characterized for the expression of both galactose-alpha (1----4)galactose-beta (Gal-Gal)-specific adhesins and pap homologous DNA. Scarring occurred in 41% and other renal abnormalities in 11% of boys infected with bacteria that did not bind Gal-Gal (Gal-Gal negative), compared with 5% and 1%, respectively, in those infected with Gal-Gal-binding strains (Gal-Gal-positive) (relative risk 8.3; 95% confidence limits 3.3 to 20.4; p less than 0.001). That boys infected with Gal-Gal-negative strains more often had reflux did not explain the increased risk for renal scarring in this group. The possibility that the phenotypically negative strains could be induced to express Gal-Gal adhesions in vivo was excluded by dot blot analysis, which showed the absence of pap homologous DNA in all but one of the Gal-Gal-negative strains. The results suggest that the absence of Gal-Gal-specific adhesins in E. coli can be used as an indicator of risk for renal scarring and the need for radiologic examination.

Adolescent

Selective use of excretory urography in women with acute pyelonephritis.

The outcome of excretory urography was analyzed in 103 nonpregnant women followed prospectively after community acquired acute pyelonephritis. Radiological abnormality was found in 40 per cent of the patients (17 per cent had major abnormalities, including renal scarring, calculi and obstruction). All 5 women with surgically correctable lesions had rapid bacteriological relapse or recurrent acute pyelonephritis. Neither a history of urinary tract infection, the acute inflammatory response nor infection due to Escherichia coli with or without adhesins specific for Gal alpha 1----4Gal beta-containing receptors was efficient in predicting major radiographic lesions or the outcome of treatment. Bacteremia was detected in 27 per cent of the patients but in the absence of obstruction. These results suggest that excretory urography is dispensable in most women with acute pyelonephritis, and that those needing such investigation may be identified by failure to respond to antibiotic treatment or by the recurrence pattern.

Acute Disease

Age-related change in anti-carbohydrate antibody levels.

It has been proposed that immunity declines with age. Most evidence for this hypothesis has been obtained from cross-sectional samples of unrelated populations that differ in age, antigen exposure, and morbidity. In the present study, the authors used serum samples collected repeatedly from the same persons in longitudinal studies. Two representative samples of the population in Göteborg, Sweden were obtained; the first was studied at ages 38, 50, and 62 years, and the second at ages 70, 75, 79, and 81 years, respectively. The phosphorylcholine determinant of pneumococcal teichoic acid and the B blood group determinant were selected as model polysaccharide antigens. The results demonstrate a consistent decline in individual antibody levels in the decades before age 70 years but not later. Antibodies to phosphorylcholine and blood group B were highly parallel, suggesting that the decline was a general phenomenon for antibodies to polysaccharide antigens.

ABO Blood-Group System

Bacterial and host determinants of renal scarring.

This review summarizes recent work examining the interaction between host and parasite in recurrent urinary tract infection (UTI) and renal scarring. Virulence in uropathogenic E. coli has been defined by the severity of acute disease. Isolates from patients with acute pyelonephritic strains differ from those causing asymptomatic bacteriuria by multiple traits which contribute to virulence, and which are coexpressed in a non-random manner. The single marker most characteristic for the pyelonephritogenic clones is bacterial adherence to uroepithelial cells binding specifically to the disaccaride Gal alpha 1-4 Gal beta within the globoseries of glycolipids. The notion that the most severe consequence of acute pyelonephritis, i.e. renal scarring, was caused by the most virulent clones, was contradicted by comparison of pyelonephritic strains isolated from children with and without scarring. The virulent clones were significantly less frequent in patients with renal scarring (22%) than in patients with recurrent pyelonephritis not developing renal scars (62%). In view of the unexpected inverse association of bacterial virulence with renal scarring lack of Gal alpha 1-4 Gal beta binding capacity of E. coli strains was found to predict the risk for renal scarring among boys with first-time acute pyelonephritis. Vesicoureteric reflux (VUR) is widely accepted as a host determinant of susceptibility to pyelonephritis and renal scarring. In our study the frequency of renal scarring was 57% among girls with VUR as compared to 8% of those without. The reflux alone did however, not explain the selection of bacteria of low virulence. Individuals prone to UTI and renal scarring were found to be a genetically selected subgroup of the general population. A correlation between P1 blood group phenotype and susceptibility to UTI and between blood group non-secretor state and renal scarring was found. The mechanisms behind these relationships need to be defined. The bacterial and host parameters combined indicate that host parameters are essential for the tendency to develop renal scarring after acute pyelonephritis.

Animals

Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection.

Interleukin-6 (IL-6) was produced in response to mucosal and systemic infection of mice with gram-negative bacteria. The IL-6 response was controlled by the lipopolysaccharide gene, Lps; in C3H/HeN mice (Lpsn/Lpsn), the urinary IL-6 levels increased within 30 min after challenge with Escherichia coli, but no response occurred in C3H/HeJ mice (Lpsd/Lpsd). In lipopolysaccharide-responder mice, the levels of local and systemic IL-6 were related to the degree of infection. The urinary response dominated after intravesical challenge, and the serum response dominated after intraperitoneal challenge. The results demonstrate that IL-6 is activated as part of lipopolysaccharide-induced mucosal and systemic responses to gram-negative bacterial infections.

Animals

Binding specificities of wild-type and cloned Escherichia coli strains that recognize globo-A.

In this study we compared the specificity for the globoseries of glycolipids of Escherichia coli expressing the O-negative, A-positive (ONAP) adhesin and clones transformed with the pap-like (prs or pap-2) gene cluster. Receptor-active glycolipids were identified by the ability of radiolabeled bacteria to bind to the glycolipids on thin-layer chromatogram plates. The ONAP adhesin and pap-like clones bound with high affinity to the globo-A and Forssman glycolipids. The ONAP strains did not recognize other glycolipids of the globoseries. In contrast, the pap-like clones also showed weak binding to globotriaosylceramide and reacted weakly with Gal alpha 1----4 Gal beta-latex beads. We suggest that the pap-like and ONAP adhesins recognize an epitope shared by the globo-A and Forssman structures, e.g., terminal GalNAc alpha 1----3 bound to Gal alpha 1----4Gal beta-containing glycolipids.

Adhesins, Escherichia coli

P blood group and proneness to urinary tract infection in Japanese children.

The globoseries of glycolipids are antigens in the P blood group system as well as epithelial cell receptors for uropathogenic Escherichia coli. The P1 blood group is overrepresented in Swedish girls with recurrent pyelonephritis. In this study, Japanese children with urinary tract infection (UTI) were analyzed for P blood group phenotype. Out of 26 children with recurrent UTI, 50% were of the P1 blood group compared to the 31% of P1 individuals in the Japanese population at large (p less than 0.05). Of children defined as having febrile UTI 62% were P1. The P1 blood group was thus significantly enriched (3.5 times) in the children with febrile UTI. These results support the hypothesis that individuals of blood group P1 run an increased risk for recurrent pyelonephritis.

Adolescent

Aerobactin production of serotyped Escherichia coli from urinary tract infections.

Aerobactin production was examined by a bioassay in 467 Escherichia coli urinary strains from girls. All strains were of known O:K:H serotype. 139, 119 and 112 strains were isolates from pyelonephritis (Py), cystitis (Cy) and asymptomatic bacteriuria (ABU), respectively, and 97 were from fecal samples of healthy girls (FN). The incidence of aerobactin production was significantly higher among Py strains than among ABU and FN strains (P less than 0.001) and also significantly higher than among Cy strains (P less than 0.01). Aerobactin production was associated with serotype, e.g. the majority of O6:K2:H1 strains and of O16:K1:H6 were positive while e.g. the O6:K13:H1 strains were negative. There was no consistent pattern of coappearance of aerobactin and hemolysin.

Bacteriuria

Bacterial virulence and inflammatory response in infants with febrile urinary tract infection or screening bacteriuria.

Two populations were analyzed prospectively after a first episode of urinary tract infection. Asymptomatic infants were screened at 2 weeks and at 3 and 10 months of age, and bacteriuria was confirmed by bladder puncture. Infants with febrile urinary tract infection were enrolled during the same study period. The inflammatory response was characterized by the presence of fever, serum C-reactive protein, microsedimentation rate, urinary leukocyte excretion, and width of the ureters. The bacteria were defined for O:K:H serotype, hemolysin production, resistance to the bactericidal effect of serum, attachment to uroepithelial cells, and specificity for the globoseries of glycolipid receptors. In agreement with previous studies, the frequency of increased inflammatory signs and of attaching Escherichia coli was significantly higher in infants with febrile urinary tract infection than in the screening group. Within both patient groups, however, children infected with attaching E. coli strains had significantly more inflammatory signs. The results suggest that adherence facilitates the presentation of bacterial components capable of causing inflammation in the tissues in the urinary tract.

Blood Sedimentation