Publications (12) View all
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Article: Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance.
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ABSTRACT: The self-assembling MexA-MexB-OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR-wt as well as a selected set of MDR single mutants distant from the proposed DNA-binding helix. Although DNA affinity and MexA-MexB-OprM repression were both drastically impaired in the selected MexR-MDR mutants, MexR-wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR-MDR mutants, secondary structure content and oligomerization properties were very similar to MexR-wt despite their lack of DNA binding. Despite this, the MexR-MDR mutants showed highly varying stabilities compared with MexR-wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA-binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR-wt in both free and DNA-bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations-stability, domain interactions, and internal hydrophobic surfaces-are also critical for the regulation of MexR DNA binding.Protein Science 04/2010; 19(4):680-92. · 2.80 Impact Factor -
Article: Individual care plans can reduce hospital admission rate for patients who frequently attend the emergency department.
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ABSTRACT: To investigate the impact, in terms of hospital admission and investigations, of individual care plans for patients who frequently attend the emergency department (ED). 32 patients who regularly attended the ED at St Thomas' Hospital were included in the study. After review of ED and hospital case records, an individual care plan was prepared for future attendances. The numbers of ED attendances, hospital admissions and investigations were collated from the electronic patient record system and compared for the 12 months prior to and 12 months after introduction of the care plan. Primary outcome measure was reduction in the number of hospital admissions (as a percentage of ED attendance). Secondary outcome measures were a reduction in the number of investigations and ED attendances. In the 12 months prior to introduction of the individual care plans, the 32 patients accounted for 858 ED attendances and 209 admissions to hospital. In 12 months after introduction of the care plans, the number of ED attendances fell to 517, with only 77 hospital admissions. Median number of hospital admissions (as a percentage of ED attendances) fell from 18.8% to 7.1% (p=0.014) after introduction of the care plan. There were also reductions in median number of ED attendances (19 vs. 5, p=0.001), median number of radiology tests (4 vs 1, p=0.001) and median number of blood tests (55 vs. 12, p<0.001). Individual care plans for a carefully selected group of patients who frequently attend the emergency department can result in a decrease in the number of hospital admissions and number of investigations.Emergency Medicine Journal 08/2011; 28(8):654-7. · 1.44 Impact Factor -
Article: Identification of species of viridans group streptococci in clinical blood culture isolates by sequence analysis of the RNase P RNA gene, rnpB.
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ABSTRACT: Viridans group streptococci (VGS) cause severe diseases such as infective endocarditis and septicaemia. Genetically, VGS species are very close to each other and it is difficult to identify them to species level with conventional methods. The aims of the present study were to use sequence analysis of the RNase P RNA gene (rnpB) to identify VGS species in clinical blood culture isolates, and to compare the results with the API 20 Strep system that is based on phenotypical characteristics. Strains from patients with septicaemia or endocarditis were analysed with PCR amplification and sequence analysis of the rnpB gene. Clinical data were registered as well. One hundred and thirty two VGS clinical blood culture isolates from patients with septicaemia (n=95) or infective endocarditis (n=36) were analysed; all but one were identified by rnpB. Streptococcus oralis, Streptococcus sanguinis and Streptococcus gordonii strains were most common in the patients with infective endocarditis. In the isolates from patients with haematological diseases, Streptococcus mitis and S. oralis dominated. In addition in 76 of the isolates it was possible to compare the results from rnpB analysis and the API 20 Strep system. In 39/76 (51%) of the isolates the results were concordant to species level; in 55 isolates there were no results from API 20 Strep. Sequence analysis of the RNase P RNA gene (rnpB) showed that almost all isolates could be identified. This could be of importance for evaluation of the portal of entry in patients with septicaemia or infective endocarditis.The Journal of infection 04/2008; 56(3):204-10. · 4.13 Impact Factor -
Article: Viridans group streptococci in blood culture isolates in a Swedish university hospital: antibiotic susceptibility and identification of erythromycin resistance genes.
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ABSTRACT: One hundred and twenty-nine isolates of viridans group streptococci in blood cultures from patients with septicaemia or endocarditis isolated between 1998 and 2003 were tested for antibiotic susceptibility to penicillin, ciprofloxacin, clindamycin, dalbavancin, daptomycin, erythromycin, linezolid, tigecycline, trimethoprim/sulphamethoxazole and vancomycin. Reduced susceptibility to penicillin (minimum inhibitory concentration (MIC) > or =0.25 microg/mL) was found in 18% of the isolates, and 4% of the strains were resistant to penicillin (MIC> or =4.0 microg/mL). Nineteen percent of the isolates had reduced susceptibility to erythromycin (MIC> or =0.5 microg/mL), among which ermB and mefA were found in 40% and 80%, respectively. Strains sequenced as Streptococcus mitis by rnpB had a high degree of non-susceptibility to erythromycin (32%) and penicillin (21%). The level of penicillin resistance in this Swedish study was lower compared with studies from other countries where the antibiotic pressure might be higher than in Sweden. Susceptibility to newer antibiotics was high; all strains were susceptible to dalbavancin, daptomycin, linezolid and vancomycin.International Journal of Antimicrobial Agents 11/2006; 28(4):292-6. · 4.13 Impact Factor -
Article: Bacteraemia in patients with hidradenitis suppurativa undergoing carbon dioxide laser surgery: detection and quantification of bacteria by lysis-filtration.
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ABSTRACT: Hidradenitis suppurativa (HS) is a cicatrising and persistent disease of apocrine gland-bearing areas in adults. The severity of this condition varies from a few suppurating lesions to widespread, disabling disease. The aetiology is obscure, but suggested contributory factors include a genetic predisposition, comedones occluding the pilosebaceous apparatus, bacterial infections, and hormonal factors. Treatment consists mainly of surgery, while medical therapies serve principally as adjunct therapy. The aim of the study was to determine the number and type of bacteria circulating in the bloodstream in patients with HS undergoing surgical treatment with a carbon dioxide laser stripping-secondary intention technique. Twenty-one patients (20 females and 1 male, mean age 36, range 20-55 years) were included in the study. One blood sample (8.3 ml) was taken before surgery, one during the operation and the last one 10 min after surgery. Five healthy persons (all females, mean age 36, range 23-48 years) not undergoing any operation were used as the controls. The blood was cultured by a lysis-filtration technique which had been shown to be very sensitive. Since the filter catches the microorganisms and colonies are formed during culturing, the number of bacteria in the samples is easily determined. In 6 patients, all samples were negative, which indicates that the method of surgery itself caused no spread of bacteria from the lesions. Bacterial growth in the first blood sample was found in 9 patients, from the second sample in 10 and from the third one in 6. In 1 patient, bacteria were detected in three samples. At least 12 bacterial species were identified. The dominating bacteria were coagulase-negative staphylococci of which most were subtyped as Staphylococcus warneri. Among the anaerobic microorganisms, Propionibacterium acnes and P.granulosum were the most frequently isolated bacteria. The bacterial findings in the blood samples accord well with the results from a previous study in which cultures were taken from the deep parts of the HS lesions. In the 5 controls, no microbial growth was detected. The carbon dioxide laser stripping technique caused no additional spread of bacteria into the bloodstream. The evaluation of cultures containing microorganisms from normal skin flora is controversial. Since the bacteria encountered in this study are in close agreement with the findings in cultures from the deeper parts of HS lesions they seem to be relevant. The growth of bacteria in the first blood sample taken before surgery may indicate that some of these patients have bacteria continuously circulating in their blood.Dermatology 02/2006; 213(4):305-12. · 2.05 Impact Factor
