Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Perfusion computed tomography in posterior circulation stroke: predictors and prognostic implications of focal hypoperfusion.

BACKGROUND AND PURPOSE: The aim was to determine the predictors of focal hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute posterior circulation stroke and its association with long-term outcome. METHODS: Patients with posterior circulation stroke were selected from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as an area of visually well demarcated mean transit time prolongation corresponding to an arterial territory on standard reconstruction CTP imaging maps. Areas of hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis Early CT Score. Clinical and imaging associations with focal hypoperfusion were identified using multiple imputation analyses, and the adjusted functional outcome measured by the modified Rankin Scale at 3 and 12 months was determined. RESULTS: Of the 3595 consecutive patients from the ASTRAL registry between 2003 and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic changes and 37.4% had focal hypoperfusion. In multiple imputation analysis, visual field deficits, reduced level of consciousness, cardiac and multiple stroke mechanisms, significant vessel pathology and ischaemic changes visible on plain CT were associated with focal hypoperfusion. Focal hypoperfusion was independently associated with outcome at 12 months (odds ratio 2.04, 95% confidence interval 1.22-3.42, P < 0.01). CONCLUSIONS: In posterior circulation stroke patients undergoing acute CTP, multiple clinical, aetiological and radiological variables were associated with focal hypoperfusion. Patients with focal hypoperfusion had a worse 12-month outcome.

[Organized Post-Stroke Care through Case Management on the Basis of a Standardized Treatment Pathway : Results of a Single-Centre Pilot Study]. / Koordinierte Schlaganfallnachsorge durch Case Management auf der Basis eines standardisierten Behandlungspfades : Ergebnisse einer monozentrischen Pilotstudie.

BACKGROUND: Post-stroke care programs based on a standardized treatment pathway supported by case management may prevent secondary stroke and minimize risk factors. OBJECTIVES: We aimed to determine the feasibility of a standardized treatment pathway and its impact on risk factor control, life-style changes and adherence to secondary prevention medication. METHODS: We conducted a prospective pilot study in consecutive stroke patients. The 12-month post-stroke care program included regular perosnal and phone contact with a certified case manager. Target values for vascular risk factors following current recommendations of stroke guidelines were monitored and treated if necessary. In the case of deviations from the treatment pathway the case manager intervened. Patients were screened for recurrent stroke at the end of the program after 12 months. RESULTS: We enrolled 101 patients: 57.4 % were male, the median age was 72 (IQR, 62-80) years, median baseline NIHSS score was 2(IQR, 1-5), 79.2 % had an ischemic stroke, 3 % a hemorrhagic stroke, and 17.8 % a transient ischemic attack (TIA). Eighty-six (85.1 %) patients completed the program, 12 (11.9 %) withdrew from the program and 3 died of malignant diseases. In total, 628 personal (6.2/patient) and 2,683 phone contacts (26.6/patient) were conducted by the case manager. Three hundred-seventy-nine specific interventions were necessary mostly because of missing medication, non-compliance, and social needs. After 12 months, target goals for blood pressure, body mass index, nicotine use, and cholesterol were more frequently (p < 0.05) achieved than at baseline. No recurrent stroke occurred during the program. CONCLUSIONS: Our pilot data demonstrate that case management-based post-stroke care is feasible and may contribute to effective secondary prevention of stroke.

Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin.

Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75(NTR)) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75(NTR) receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury-induced loss of DRG neurons. This result demonstrates that previous findings linking p75(NTR) and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS.

Multimodal Computed Tomography Based Definition of Cerebral Imaging Profiles for Acute Stroke Reperfusion Therapy (CT-DEFINE): Results of a Prospective Observational Study.

PURPOSE: To prospectively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy. METHODS: Anterior circulation stroke patients underwent non-contrast CT (NCCT), CT-angiography, and CT-perfusion within 12 h from symptom-onset. Patients could be treated with intravenous-tissue plasminogen activator (IV-tPA), endovascular or combined reperfusion therapies. Cerebral imaging profiles (IP) were NCCT-Alberta Stroke Program Early CT Score (ASPECTS) > 7 (IP1); NCCT-ASPECTS > 5 and proximal occlusion on CT-angiography (IP2); CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS, and cerebral blood flow (CBF)-ASPECTS ≥ 2 (IP3). Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months. RESULTS: Of 102 included patients, 62 (61%) received any reperfusion therapy. In IP2 and IP3, favorable outcome was more frequent in patients with reperfusion therapy than in those without; however, this did not reach statistical significance (IP2: 39% vs 15%, p = 0.26; IP3: 50% vs 17 %; p = 0.31). No difference was seen in IP1 (58% vs 58%, p = 1.0). In IP2, patients with IV-tPA alone achieved better functional outcome (50% vs 11%, p = 0.03) and lower mortality (0% vs 28%, p = 0.045) than those without. CONCLUSIONS: Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infarction and a visible intracranial occlusion in patients receiving IV-tPA. Reperfusion therapy may be futile in patients without proven vessel occlusion.

Analgesic efficacy with rapidly absorbed ibuprofen sodium dihydrate in postsurgical dental pain: results from the randomized QUIKK trial.

OBJECTIVE: To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid). MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, crossover trial, patients requiring surgical removal of two impacted or partially impacted mandibular third molars received: ibuprofen sodium dihydrate 400 mg plus conventional ibuprofen placebo (Group 1); or conventional ibuprofen 400 mg plus ibuprofen sodium dihydrate placebo (Group 2) following the first surgery. Patients were then crossed over to the alternative treatment. RESULTS: 72 patients were enrolled in Group 1 and 72 patients in Group 2. Ibuprofen sodium dihydrate produced faster initial pain relief than conventional ibuprofen as assessed by time to first pain relief (24.6 vs. 30.5 minutes; p = 0.004), and patient-assessed pain relief at 15 minutes ("some" to "complete" pain relief: 43% vs. 29%; p < 0.001) and 30 minutes (82% vs. 63%; p < 0.001) and pain intensity at 30 minutes (p < 0.001). Substantial pain relief with ibuprofen sodium dihydrate was twice that of conventional ibuprofen at 30 minutes (11% vs. 5%; not significant); 29% and 33% of patients did not reach substantial pain relief at 120 minutes. There were no adverse events leading to treatment discontinuation and only two serious adverse events (oral abscess and facial paresis with conventional ibuprofen) considered unrelated to treatment. CONCLUSIONS: Ibuprofen sodium dihydrate was as effective as conventional ibuprofen, but had a faster onset of initial pain relief and significantly reduced pain intensity within the first 30 minutes after administration, providing rapid clinically meaningful pain relief for patients.

Characterization of human mucin (MUC15) and identification of ovine and caprine orthologs.

The glycoprotein MUC15 (mucin 15) was initially isolated from the bovine milk fat globule membrane. The present work demonstrates the existence of immunologically similar proteins ( approximately 130 kDa) in ovine, caprine, porcine, and buffalo milk samples. Purification and N-terminal amino acid sequencing confirmed the presence of ovine and caprine MUC15 orthologs in milk fat globule membranes. Expression of MUC15 in human milk was demonstrated by immunostaining ( approximately 150 kDa) as well as by mass spectrometry. Screening of a human multiple tissue expression array showed abundant MUC15 gene expression in placenta, salivary gland, thyroid gland, trachea, esophagus, kidney, testis, and the leukemia K-562 cell line. Furthermore, moderate expression was seen in the pancreas, adult and fetal lung, fetal kidney, lymph node, adult and fetal thymus, and parietal lobe. Structural motifs for interactions (epidermal growth factor receptor and Src homology 2 domains) are identified in the intracellular region. Implication of the mucin in signal transduction and the potential physiological function of MUC15 are discussed.

Epidemiology of European community-associated methicillin-resistant Staphylococcus aureus clonal complex 80 type IV strains isolated in Denmark from 1993 to 2004.

In Europe, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been caused predominantly by isolates belonging to the "European CA-MRSA" clone (sequence type 80, staphylococcal cassette chromosome mec type IV). In this study, the epidemiology of European CA-MRSA was investigated on a nationwide scale, covering the period from 1993 to 2004. Denmark has been a low-prevalence country regarding MRSA since the mid-1970s but has experienced an increase in the number of new MRSA cases in recent years. Our results show that European CA-MRSA contributed to this increase. The isolates primarily caused skin and soft tissue infections (SSTIs) in patients outside hospitals, and transmission between household members was the predominant mode of spread. Although some of the isolates were found in hospitalized patients, nosocomial transmission seemed likely in only one instance, pointing to endogenous infections as an important factor. Compared to the CA-MRSA clone most common in the United States (USA300), the European CA-MRSA clone seems less well adapted to persist in hospital environments. Patients with a recent history of travel or family relation to the Mediterranean or Middle East were highly overrepresented. The epidemiological data indicated that the European CA-MRSA isolates were introduced into Denmark on multiple occasions, paralleled by an increasing level of genetic diversity of the isolates found during the study period. European CA-MRSA has previously been described as a rather uniform clone. However, we found pronounced, diverse pulsed-field gel electrophoresis subtypes, staphylococcal protein A gene (spa) types, and susceptibility patterns.

Characterization of carbohydrate structures of bovine MUC15 and distribution of the mucin in bovine milk.

The present work reports the characterization of carbohydrate structures and the distribution of the newly identified mucin MUC15, a highly glycosylated protein associated with the bovine milk fat globule membrane (MFGM). Distribution of MUC15 was investigated in various fractions of bovine milk by densitometric scanning of Western blots. In raw milk, MUC15 was shown to constitute 0.08% (wt) of the protein and approximately 1.5% (wt) of the MFGM-associated proteins. Surprisingly, this study showed that in addition to the fat-containing fractions, such as MFGM and buttermilk, MUC15 was present in nonfat-containing fractions as well, such as skim milk and whey. Compositional and structural studies of the carbohydrates of bovine milk MUC15 showed that the glycans are composed of fucose, galactose, mannose, N-acetylgalactosamine, N-acetylglycosamine, and sialic acid. The carbohydrate was shown to constitute 65% of the total molecular weight, and the molar ratios of the individual sugars to protein of the O-linked glycans were determined. The glycan structures of MUC15 were further studied by enzymatic deglycosylation experiments using different endo- and exoglycosidases as well as a panel of lectins. The N-linked glycans were shown to contain mainly hybrid-type N-glycans. In addition, the N-glycans were shown to be sialylated and contain terminal poly-lactosamine structures. The O-linked glycans were found to constitute some unsubstituted Core-1 structures and a substantial number of sialylated Core-1 O-linked glycans. By comparing the results of peanut agglutinin lectin binding, enzymatic deglycosylation, and monosaccharide composition analysis, we concluded that bovine MUC15 also contains more complex O-glycans containing high amounts N-acetylglucosamine residues. Furthermore, a small subset of the O-linked glycans is decorated with lactosamine on their terminal ends.

Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000.

Staphylococcus aureus is a leading cause of bacteraemia. This study analysed temporal trends from 18,702 adult cases of S. aureus bacteraemia in Denmark between 1981 and 2000. After stratification for mode of acquisition, 57% of cases were hospital-acquired (HA), 28% were community-acquired (CA) and 15% were of undetermined acquisition (UA). Incidence rates increased from 18.2 to 30.5 cases/100,000 population. Annual rates increased by 6.4% for CA, by 2.2% for HA and by 3.6% for UA cases, respectively. Case-mortality associated with HA bacteraemia decreased from 36.2% to 20.7% (43% rate reduction, p 0.0001), compared with a decrease from 34.5% to 26.5% (23% rate reduction, p 0.0001) for CA bacteraemia. Following multivariate analysis, age, pneumonia, endocarditis and chronic illness were associated with increased mortality, regardless of the mode of acquisition. Overall, mortality associated with S. aureus bacteraemia declined significantly between 1981 and 2000, but incidence rates doubled, so that the total number of deaths increased. These data emphasise the public health importance of S. aureus bacteraemia and the need for further preventive measures and improved care in order to reduce incidence rates and improve outcomes.

Inhibitory effects of human and bovine milk constituents on rotavirus infections.

Among etiologic agents, rotavirus is the major cause of severe dehydration diarrhea in infant mammals. In vitro and in vivo studies have indicated that the human milk-fat globule protein lactadherin inhibits rotavirus binding and protects breast-fed children against symptomatic rotavirus infection. The present work was conducted to evaluate the effect of lactadherin, along with some other milk proteins and fractions, on rotavirus infections in MA104 and Caco-2 cell lines. It is shown that human, and not bovine, lactadherin inhibits Wa rotavirus infection in vitro. Human lactadherin seems to act through a mechanism involving protein-virus interactions. The reason for the activity of human lactadherin is not clear, but it might lie within differences in the protein structure or the attached oligosaccharides. Likewise, in our hands, bovine lactoferrin did not show any suppressive activity against rotavirus. In contrast, MUC1 from bovine milk inhibits the neuraminidase-sensitive rotavirus RRV strain efficiently, whereas it has no effect on the neuraminidase-resistant Wa strain. Finally, a bovine macromolecular whey protein fraction turned out to have an efficient and versatile inhibitory activity against rotavirus.

Purification of MUC1 from bovine milk-fat globules and characterization of a corresponding full-length cDNA clone.

The highly glycosylated protein MUC1 was purified from bovine milk-fat globule membranes by a procedure involving detergent extraction, ion-exchange chromatography and reverse-phase chromatography. The identity of the purified mucin protein was confirmed by N-terminal sequencing and partial amino acid sequences obtained by peptide mapping. The complete amino acid sequence of MUC1 was determined by cloning and sequencing the corresponding bovine mammary gland cDNA, which was shown to encode a protein of 580 amino acid residues comprising a cleavable signal peptide of 22 residues. The deduced amino acid sequence demonstrated structural features characteristic for mucins, including an extracellular tandem repeat region with 11 partially conserved repeats (20 amino acids each), a membrane-proximal SEA module, a transmembrane domain, and a cytoplasmic C-terminal region. Monosaccharide composition determinations suggested significant structural differences between O-linked glycans of MUC1 originating from either bovine or human milk. Interspecies differences of the consensus repeat sequence in MUC1 and the physiological functions are discussed.

A 41-year history of a mandibular subperiosteal implant.

The subperiosteal implant was originally described in the 1940s. The inadequate long-term results of subperiosteal implants are in contrast to the excellent results documented for endosseous osseointegrated oral implants. Consequently, subperiosteal implants and other soft-tissue-anchored implants should not be used presently. Furthermore, these implants are seldom seen today, because they generally were removed rather shortly after placement. The present report documents a full 41-year history of a mandibular subperiosteal implant inserted in 1957 by focusing upon the consequences of not removing an implant in spite of continuous periods of complications during 4 decades. Implant exposure, inflammation, infection, and fistula formation occurred persistently. Total implant removal was refused by the patient in 1973. After 25 years without control, tremendous resorption of the mandible was observed in 1998. Consequently, the entire implant was then removed. Placement of osseointegrated oral implants was impossible without extensive autogenous bone grafting. The present report has demonstrated that regular control of patients with subperiosteal implants is mandatory. Furthermore, subperiosteal implants should definitely be removed, if continuous periods of complications occur.

Evaluation of a new 3-h hybridization method for detecting the mecA gene in Staphylococcus aureus and comparison with existing genotypic and phenotypic susceptibility testing methods.

A new 3-h hybridization assay for detection of the staphylococcal mecA gene and the Staphylococcus aureus nuclease gene was evaluated by comparing the assay with existing genotypic and phenotypic methods. A total of 275 S. aureus strains were tested, including 257 epidemiologically unrelated strains (135 mecA-positive and 122 mecA-negative; collection I), and 18 strains with known borderline resistance to methicillin (collection II). Complete agreement was obtained for both collections when comparing the new assay with genotypic methods. We further evaluated a range of phenotypic susceptibility methods recommended in Europe and/or USA using the presence of the mecA gene as the defining standard. For collection I a high degree of agreement was found for both Etests (256 strains) and the oxacillin screen plate test (255 strains); the degree of agreement was lower for agar dilution methicillin (250 strains) and oxacillin 1 microg discs (239 strains). For the borderline strains a high degree of agreement was only obtained by the oxacillin screen plate test (17 of 18 strains). The other tests were less accurate, in the following order: agar dilution methicillin, Etest methicillin, Etest oxacillin and oxacillin discs with disagreement for four, five, nine and 13 strains, respectively. In conclusion, the new hybridization assay is a rapid and exact method for detecting the mecA gene and the S. aureus nuclease gene. This study confirms that phenotypic tests for methicillin resistance in S. aureus strains creates both false-susceptible and false-resistant results, especially for borderline resistant strains.

Detection of clinical vancomycin-resistant enterococci in Denmark by multiplex PCR and sandwich hybridization.

Since the first cases of human infection with vancomycin-resistant enterococci (VRE) were reported in the late eighties, there has been a dramatic increase in VRE all over the world. So far, there have not been any reports of clinical VRE in Denmark. In this study we have investigated 131 clinically important enterococci sent to Statens Serum Institut from all over Denmark during the period July 1995 to May 1997. The susceptibility to vancomycin, teicoplanin, ampicillin and gentamicin was tested by the agar dilution method. In addition, two methods were developed to detect the different genotypes of glycopeptide resistance described in enterococci: a multiplex PCR assay for detection of vanA, vanB, vanC-1, vanC-2/3 ligase genes including 16S rRNA gene control primers and a sandwich hybridization assay to confirm vanA and vanB PCR-positive strains. The highest frequency of resistance to the tested antibiotics was found in the Enterococcus faecium group. Four strains were found with acquired resistance to glycopeptides: one E. faecium and one E. gallinarum were vanA positive, and two E. faecium isolates were vanB positive. These strains were isolated from different hospitals in different periods of time, and all patients recovered from their infections with VRE. Today, the PCR and sandwich hybridization methods are used for screening of vancomycin-resistant enterococci in humans as part of the Danish surveillance programme.

Glycopeptide susceptibility among Danish Enterococcus faecium and Enterococcus faecalis isolates of animal and human origin and PCR identification of genes within the VanA cluster.

The MICs of vancomycin and avoparcin were determined for isolates of Enterococcus faecium and isolates of Enterococcus faecalis recovered from the feces of humans and animals in Denmark. Two hundred twenty-one of 376 (59%) isolates of E. faecium and 2 of 133 (1.5%) isolates of E. faecalis were resistant to vancomycin (MICs, 128 to > or = 256 micrograms/ml), and all vancomycin-resistant isolates were resistant to avoparcin (MICs, 64 to > or = 256 micrograms/ml). All vancomycin-resistant isolates examined carried the vanA, vanX, and vanR genes, suggesting that a gene cluster similar to that of the transposon Tn1546 was responsible for the resistance.

Vancomycin-resistant enterococci at a large university hospital in Denmark.

Enterococci are part of the normal human fecal flora and also part of the fecal flora of many animals. Vancomycin- and ampicillin-resistant enterococci give rise to infections that may virtually be untreatable with antibiotics. Antibiotic use in humans is a risk factor for development or selection of vancomycin-resistant enterococci. In animals the related glycopeptide avoparcin is used, especially in poultry, as a food additive to promote growth. Selective pressures for vancomycin-resistant enterococci are high in Denmark with the production of 105 million poultry and the use of 24,000 kg avoparcin per year. The possible impact on vancomycin resistance among human isolates of enterococci remains to be defined. Furthermore, there has been a 3-fold increase in vancomycin usage during the last 5 years at our hospital, from 2.4 to 7 kg/year. We examined 91 stool specimens from 67 patients in risk units at our hospital. Using a selective medium (KAA agar), 17 strains of Enterococcus faecium grew on the selective medium and 3 (18%) were vancomycin-resistant (MIC > 256 mg/l). Using PCR and an internal probe, vanA was found in the vancomycin-resistant enterococci. No association between vancomycin therapy and carriage of VRE was demonstrated in these patients.

Linker insertion analysis of the FimH adhesin of type 1 fimbriae in an Escherichia coli fimH-null background.

The gene encoding the Escherichia coli FimH adhesin of type 1 fimbriae has been subjected to linker insertion mutagenesis. Amino acid changes were introduced at a number of positions spanning the entire sequence in order to probe the structure-function relationship of the FimH protein. The effect of these mutations on the ability of bacteria to express a D-mannose binding phenotype was assessed in a fimH null mutant (MS4) constructed by allelic exchange in the E. coli K-12 strain PC31. Mutations mapping at amino acid residues 36, 58 and 279 of the mature FimH protein were shown to completely abolish binding to D-mannose receptors. Differences in the level of fimbriation were also observed as a result of some of the mutations in the fimH gene. These mutants may prove useful in dissecting receptor-ligand interactions by defining regions of the FimH protein that are important in erythrocyte binding.

Selection of multiple resistance in Salmonella enteritidis during treatment with ciprofloxacin.

We report on a strain of Salmonella enteritidis which was found to be resistant to both ciprofloxacin and beta-lactams and chloramphenicol in a patient treated with ciprofloxacin for a splenic abscess. We conclude that in invasive infections such as a splenic abscess caused by Salmonella, early surgical intervention is important. Multiple-drug-resistant strains of Salmonella may be selected by treatment with ciprofloxacin alone.

Chimeric FimH adhesin of type 1 fimbriae: a bacterial surface display system for heterologous sequences.

The FimH adhesin of type 1 fimbriae has been tested as a display system for heterologous protein segments on the surface of Escherichia coli. This was carried out by introduction of restriction site handles (BglII sites) in two different positions in the fimH gene, followed by in-frame insertion of heterologous DNA segments encoding two reporter sequences. In the selected positions such insertions did not significantly alter the function of the FimH protein with regard to surface location and adhesive ability. The system seemed to be quite flexible, since chimeric versions of the FimH adhesin containing as many as 56 foreign amino acids were transported to the bacterial surface as components of the fimbrial organelles. Furthermore, the foreign protein segments were recognized by insert-specific antibodies when expressed within chimeric proteins on the surface of the bacteria. The results from this feasibility study point to the possibility of using the FimH adhesin as a general surface display system for sizeable protein segments.