| 1. |
|
|
| 2. |
- Daniels, Robert, et al.
(författare)
-
Disulfide Bond Formation and Cysteine Exclusion in Gram-positive Bacteria
- 2010
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:5, s. 3300-3309
-
Tidskriftsartikel (refereegranskat)abstract
- Most secretion pathways in bacteria and eukaryotic cells are challenged by the requirement for their substrate proteins to mature after they traverse a membrane barrier and enter a reactive oxidizing environment. For Gram-positive bacteria, the mechanisms that protect their exported proteins from misoxidation during their post-translocation maturation are poorly understood. To address this, we separated numerous bacterial species according to their tolerance for oxygen and divided their proteomes based on the predicted subcellular localization of their proteins. We then applied a previously established computational approach that utilizes cysteine incorporation patterns in proteins as an indicator of enzymatic systems that may exist in each species. The Sec-dependent exported proteins from aerobic Gram-positive Actinobacteria were found to encode cysteines in an even-biased pattern indicative of a functional disulfide bond formation system. In contrast, aerobic Gram-positive Firmicutes favor the exclusion of cysteines from both their cytoplasmic proteins and their substantially longer exported proteins. Supporting these findings, we show that Firmicutes, but not Actinobacteria, tolerate growth in reductant. We further demonstrate that the actinobacterium Corynebacterium glutamicum possesses disulfide-bonded proteins and two dimeric Dsb-like enzymes that can efficiently catalyze the formation of disulfide bonds. Our results suggest that cysteine exclusion is an important adaptive strategy against the challenges presented by oxidative environments.
|
|
| 3. |
- Lopez-Valladares, Gloria, 1963-, et al.
(författare)
-
Human isolates of Listeria monocytogenes in Sweden during half a century (1958-2010)
- 2014
-
Ingår i: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 142, s. 2251-2260
-
Tidskriftsartikel (refereegranskat)abstract
- Isolates of Listeria monocytogenes (n=932) isolated in Sweden during 1958–2010 from human patients with invasive listeriosis were characterized by serotyping and pulsed-field gel electrophoresis (PFGE) (AscI). Of the 932 isolates, 183 different PFGE types were identified, of which 83 were each represented by only one isolate. In all, 483 serovar 1/2a isolates were distributed over 114 PFGE types; 90 serovar 1/2b isolates gave 32 PFGE types; 21 serovar 1/2c isolates gave nine PFGE types; three serovar 3b isolates gave one PFGE type; and, 335 serovar 4b isolates gave 31 PFGE types. During the 1980s in Sweden, several serovar 4b cases were associated with the consumption of European raw soft cheese. However, as cheese-production hygiene has improved, the number of 4b cases has decreased. Since 1996, serovar 1/2a has been the dominant L. monocytogenes serovar in human listeriosis in Sweden. Therefore, based on current serovars and PFGE types, an association between human cases of listeriosis and the consumption of vacuum-packed gravad and cold-smoked salmon is suggested.
|
|
| 4. |
- Mellroth, Peter, et al.
(författare)
-
LytA, Major Autolysin of Streptococcus pneumoniae, Requires Access to Nascent Peptidoglycan
- 2012
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:14, s. 11018-11029
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The regulation of cell wall hydrolysis by the pneumococcal autolysin LytA is poorly understood. Results: The cell wall is susceptible to extracellular LytA only during the stationary phase or after cell wall synthesis inhibition. Conclusion: LytA is regulated on the substrate level, where peptidoglycan modifications likely prevent LytA hydrolysis. Significance: The control of amidases is essential for bacterial survival, cell-wall synthesis, and division.
|
|
| 5. |
- Mellroth, Peter, et al.
(författare)
-
Structural and Functional Insights into Peptidoglycan Access for the Lytic Amidase LytA of Streptococcus pneumoniae
- 2014
-
Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 5:1, s. e01120-13-
-
Tidskriftsartikel (refereegranskat)abstract
- The cytosolic N-acetylmuramoyl-L-alanine amidase LytA protein of Streptococcus pneumoniae, which is released by bacterial lysis, associates with the cell wall via its choline-binding motif. During exponential growth, LytA accesses its peptidoglycan substrate to cause lysis only when nascent peptidoglycan synthesis is stalled by nutrient starvation or beta-lactam antibiotics. Here we present three-dimensional structures of LytA and establish the requirements for substrate binding and catalytic activity. The solution structure of the full-length LytA dimer reveals a peculiar fold, with the choline-binding domains forming a rigid V-shaped scaffold and the relatively more flexible amidase domains attached in a trans position. The 1.05-angstrom crystal structure of the amidase domain reveals a prominent Y-shaped binding crevice composed of three contiguous subregions, with a zinc-containing active site localized at the bottom of the branch point. Site-directed mutagenesis was employed to identify catalytic residues and to investigate the relative impact of potential substrate-interacting residues lining the binding crevice for the lytic activity of LytA. In vitro activity assays using defined muropeptide substrates reveal that LytA utilizes a large substrate recognition interface and requires large muropeptide substrates with several connected saccharides that interact with all subregions of the binding crevice for catalysis. We hypothesize that the substrate requirements restrict LytA to the sites on the cell wall where nascent peptidoglycan synthesis occurs. IMPORTANCE Streptococcus pneumoniae is a human respiratory tract pathogen responsible for millions of deaths annually. Its major pneumococcal autolysin, LytA, is required for autolysis and fratricidal lysis and functions as a virulence factor that facilitates the spread of toxins and factors involved in immune evasion. LytA is also activated by penicillin and vancomycin and is responsible for the lysis induced by these antibiotics. The factors that regulate the lytic activity of LytA are unclear, but it was recently demonstrated that control is at the level of substrate recognition and that LytA required access to the nascent peptidoglycan. The present study was undertaken to structurally and functionally investigate LytA and its substrate-interacting interface and to determine the requirements for substrate recognition and catalysis. Our results reveal that the amidase domain comprises a complex substrate-binding crevice and needs to interact with a large-motif epitope of peptidoglycan for catalysis.
|
|
| 6. |
- Browall, Sarah, et al.
(författare)
-
Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types
- 2014
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 44:6, s. 1646-1657
-
Tidskriftsartikel (refereegranskat)abstract
- Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored.Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children.The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality.PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.
|
|
| 7. |
- Linner, Anna, et al.
(författare)
-
Clinical Efficacy of Polyspecific Intravenous Immunoglobulin Therapy in Patients With Streptococcal Toxic Shock Syndrome : A Comparative Observational Study
- 2014
-
Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 59:6, s. 851-857
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. Methods. The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. Results. Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). Conclusions. This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS.
|
|
| 8. |
- Skovbjerg, Susann, 1973, et al.
(författare)
-
Low rate of pneumococci non-susceptible to penicillin in healthy Swedish toddlers.
- 2013
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:4, s. 279-284
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Infection caused by Streptococcus pneumoniae is the leading cause of mortality in children worldwide. The aim of this study was to determine if a noted increase in non-susceptibility to penicillin among pneumococcal clinical isolates from young children reflected a similar increase in healthy children. Methods: During 2004-2005, before the conjugate pneumococcal vaccine was introduced in Sweden, 663 healthy children (13-24 months of age) attending 17 child health centres in Gothenburg, Sweden, were cultured for bacteria in the nasopharynx. Social factors were identified through a parental questionnaire. Pneumococcal serotypes and antibiotic resistance rates were determined. Antibiotic resistance was also monitored in 162 simultaneously obtained nasopharyngeal pneumococci isolated from clinical samples. Results: The healthy children frequently carried pneumococci (45%), Moraxella catarrhalis (54%), and Haemophilus influenzae (22%). The carriage rates for all these pathogens were higher in children attending day care centres compared to children staying at home (p < 0.001). The dominating pneumococcal serotypes were 6B, 19F, 23F, and 6A. Non-susceptibility to penicillin was low (4.0%) and only exceeded by that to trimethoprim-sulfamethoxazole (9.8%). Both rates were higher in the clinical isolates (9.3% and 16.7%, respectively; p < 0.05). No relationships to geographic area, day care attendance, recent antibiotic use, or travel abroad were shown for any specific serotype or for the presence of penicillin-non-susceptible pneumococci in the healthy children. Conclusions: Pneumococcal resistance rates in the healthy child population were low and did not reflect the higher rates noted at the laboratory in clinical samples obtained before and during the study.
|
|
