1.
Aspholm-Hurtig, Marina, et al.
(författare)
Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
2004
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
Tidskriftsartikel (refereegranskat) abstract
Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
2.
Eklund, Erik, et al.
(författare)
Proteoglycan production in disomic and trisomy 7-carrying human synovial cells.
2002
Ingår i: Matrix Biology. - 1569-1802. ; 21:4, s. 325-335
Tidskriftsartikel (refereegranskat) abstract
To gain further insight into the synthesis and structure of the synovial matrix of joints, we have established cell cultures from synovial specimens and elaborated their production of hyaluronan and proteoglycans. The cultures secreted mainly the small proteoglycan decorin, but also considerable amounts of the related biglycan and the large proteoglycan versican. Only minor amounts of heparan sulfate proteoglycans were found. All cultures also had a high production of hyaluronan, which highlights the important role for normal joint function of these cells. In joint diseases, a common feature is the presence of an extra chromosome 7 (trisomy 7) in the synovial cells. To study the possible consequences of trisomy 7 on the synovial cell function, we extended our study to cultures that had been sub-cloned to contain high amounts of trisomy 7-carrying cells. These cell cultures had approximately four times more versican than their disomic counterparts in the cell culture medium, indicating that versican may be a mediator in the processes of joint destructive disorders. To find an explanation for this increase in versican, we investigated the expression/secretion of PDGF-AA and IL-6, cytokines with their genes located to chromosome 7. Indeed, both these cytokines were increased in the cultures with high frequencies of trisomy 7. We then added the two cytokines to cell cultures of disomic synovial cells, but only cells treated with IL-6 displayed an increased amount of versican. Thus, we suggest that the increased amount of versican in cultures of trisomy 7-carrying cells relates to an autocrine loop involving an increased IL-6 production.
3.
Okroj, Marcin, et al.
(författare)
Antibodies against Kaposi sarcoma-associated herpes virus (KSHV) complement control protein (KCP) in infected individuals
2007
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 25:48, s. 8102-8109
Tidskriftsartikel (refereegranskat) abstract
Kaposi sarcoma-associated herpesvirus (KSHV) is the most important etiopathological factor of Kaposi's sarcoma (KS) and some specific types of malignant lymphomas. One of the viral lytic genes encodes the KSHV complement control protein (KCP), which functionally mimics human complement inhibitors. Although this protein provides an advantage for evading the complement attack, it can serve as target for adaptive immune response. Herein, we identified anti-KCP IgG antibodies in patients with KS and KSHV-related lymphomas. KCP-specific antibodies were only detected in sera of those patients who had high titres of antibodies against lytic or latent KSHV antigens. Complement control protein domain 2 (CCP2) was found to be the most immunogenic part of the KCP protein. Furthermore, pre-incubation of KCP-expressing CHO cells with patient sera containing anti-KCP antibodies resulted in an increased complement deposition when incubated with human serum.
4.
Okroj, Marcin, et al.
(författare)
Prevalence of antibodies against Kaposi's sarcoma associated herpes virus (KSHV) complement inhibitory protein (KCP) in KSHV-related diseases and their correlation with clinical parameters.
2011
Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 29, s. 1129-1134
Tidskriftsartikel (refereegranskat) abstract
Kaposi's sarcoma-associated herpes virus (KSHV) encodes its own inhibitor of the complement system, designated KSHV complement control protein (KCP). Previously, we detected anti-KCP antibodies in a small group of 22 patients suffering from Kaposi's sarcoma (KS) and KSHV-related lymphoproliferative diseases (Vaccine, 25:8102-9). Anti-KCP antibodies were more prevalent in individuals suffering from KSHV-related lymphomas than KS and also in those with high titer of antibodies against lytic KSHV antigens. Herein we analyze anti-KCP antibodies in 175 individuals originating from three different groups from northern Sweden or Italy, which included patients suffering from classical or HIV-associated KS, Multicentric Castleman's Disease, KSHV-associated solid lymphoma, pleural effusion lymphoma and healthy individuals with detectable KSHV immune response. Our current study confirmed previous observations concerning antibody prevalence but we also analyzed correlations between anti-KCP antibodies and classical KS evolution, clinical stage and viral load in body fluids. Furthermore, we show that patient's anti-KCP antibodies are able to decrease the ability of KCP to inhibit complement. This fact combined with results of statistical analysis suggests that KCP inactivation by specific antibodies may influence progression of classical KS.
5.
Forsman, L. Davies, et al.
(författare)
Intra- and Extracellular Activities of Trimethoprim-Sulfamethoxazole against Susceptible and Multidrug-Resistant Mycobacterium tuberculosis
2014
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 58:12, s. 7557-7559
Tidskriftsartikel (refereegranskat) abstract
We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC(0-24)/MIC) using >= 25 as a potential target, the cumulative fraction response was >= 90% at doses of >= 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.
6.
Ripamonti, Chiara, et al.
(författare)
Biological and genetic evolution of HIV type 1 in two siblings with different patterns of disease progression
2007
Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 23:12, s. 1531-1540
Tidskriftsartikel (refereegranskat) abstract
To investigate the immunological and virological factors that may lead to different patterns of disease progression characteristic of HIV-1-infected children, two HIV-1-infected siblings, a slow and a fast progressor, were followed prospectively before the onset of highly active antiretroviral therapy. Viral coreceptor usage, including the use of CCR5/CXCR4 chimeric receptors, macrophage tropism, and sensitivity to the CC-chemokine RANTES, has been studied. An autologous and heterologous neutralizing antibody response has been documented using peripheral blood mononuclear cells- and GHOST(3) cell line-based assays. Viral evolution was investigated by env C2-V3 region sequence analysis. Although both siblings were infected with HIV-1 of the R5 phenotype, their viruses showed important biological differences. In the fast progressor there was a higher RANTES sensitivity of the early virus, an increased trend to change the mode of CCR5 receptor use, and a larger genetic evolution. Both children developed an autologous neutralizing antibody response starting from the second year with evidence of the continuous emergence of resistant variants. A marked viral genetic and phenotypic evolution was documented in the fast progressor sibling, which is accompanied by a high viral RANTES sensitivity and persistent neutralizing antibodies.
7.
Bratanis, Eleni
(författare)
Bacterial antibody hydrolyzing enzymes – as bacterial virulence factors and biotechnological tools
2019
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Antibodies are an essential part of the human immune system, and antibody mediated immunity has been an area of interest for many researchers for almost a century. An accumulation of knowledge regarding antibody structure, glycosylation and receptor interactions has contributed to the current understanding of antibody mediated immunity. It has more recently become evident how bacteria and other microorganisms evade host recognition and eradication through specific antibody degradation or modification. The importance of antibody glycosylation and how glycan modification can fine-tune the elicited immune response has also contributed to the development of antibody-based drugs with improved clinical efficacy. In turn these insights have paved the way and created a need for the development of biotechnological methods and tools to specifically engineer antibodies with defined properties, for analysis to ensure quality and safety, and for improved antibody purification.This thesis highlights the importance of glycosylation for antibody function and presents different aspects and applications of antibody modifications by bacteria. We show, for the first time, activity of the IgG-specific Streptococcal endoglycosidase EndoS during Streptococcus pyogenes infection, clearly demonstrating that EndoS contributes to S. pyogenes pathogenesis and bacterial survival in the context of adaptive immunity. Further this thesis presents the use of bacterial enzymes as antibody modifying tools and their potential as binding reagents for selective antibody purification. The identification and characterization of two novel proteases, BspK and BspE exhibiting unique IgG and IgA cleavage profiles respectively, from Bdellovibrio bacteriovorus highlights the potential of using Bdellovibrio as a source for the identification of novel enzymes with biotechnological applications. Finally, I present the development of a novel method for selective antibody purification, using the inactive variants of the bacterial enzymes EndoS and EndoS2, ensuring the purification of native, correctly folded and modified antibodies.
8.
Janson, Håkan, et al.
(författare)
Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae: cloning, nucleotide sequence, and expression in Escherichia coli
1991
Ingår i: Infection and Immunity. - 1098-5522. ; 59:1, s. 119-125
Tidskriftsartikel (refereegranskat) abstract
The gene for protein D, a membrane-associated protein with specific affinity for human immunoglobulin D, was cloned from a nontypeable strain of Haemophilus influenzae. The gene was expressed in Escherichia coli from an endogenous promoter, and the gene product has an apparent molecular weight equal to that of H. influenzae protein D (42,000). The complete nucleotide sequence of the gene for protein D was determined, and the deduced amino acid sequence of 364 residues includes a putative signal sequence of 18 amino acids containing a consensus sequence, Leu-Ala-Gly-Cys, for bacterial lipoproteins. The sequence of protein D shows no similarity to those of other immunoglobulin-binding proteins. Protein D is the first example of immunoglobulin receptors from gram-negative bacteria that has been cloned and sequenced.
9.
Jasir, Aftab, et al.
(författare)
New antimicrobial peptide active against Gram-positive pathogens
2004
Ingår i: Indian Journal of Medical Research. - 0971-5916. ; 119:Suppl., s. 74-76
Tidskriftsartikel (refereegranskat) abstract
Background & objectives: Human and animal cystatins have been shown to inhibit the replication of certain viruses and bacteria, though it is not directly demonstrated that the effects are due to protease inhibitory capacity of the cystatins. We report antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(N-alpha-benzyloxycarbonyl-arginyl-leucylamido)-1-(E)-cinnamoyla mido-3-methylbutane, structurally based upon the aminoterminal segment of the inhibitory centre of the human cysteine protease inhibitor, cystatin C. Methods: Clinical isolates of group A, B, C and G streptococci were collected. The antibacterial activity of Cystapep 1 derivative was tested by agar well diffusion method. Results: Cystapep 1, displayed antibacterial activity against several clinically important Gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 mug/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against Gram-negative bacteria was observed. Interpretation & conclusion: Cystapep 1 also showed high activity against methicillin-resistant Staph. aureus (MRSA) and multi-antibiotic resistant coagulase negative staphylococci (CNS), suggesting its mechanism of action to be different from most currently used antibiotics.
10.
