Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Environ Geochem Health ; 46(4): 137, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483759

ABSTRACT

Lacustrine sediment quality indicates the effects of both natural and anthropogenic activities on the ecosystem and communities. Despite its ecological importance, myriad complexities, and potential contaminant sources, the spatial distribution of surficial sediments in Lake Victoria's Winam Gulf has never been comprehensively documented. The purpose of this study was to assess the spatial distribution, pathways, and ecological risk of metal elements in the lake using a sediment matrix. Sediment samples were collected throughout the gulf in November 2022. The concentrations of Al, As, Cd, Co, Cr, Cu, Fe, K, Mn, Mo, Ni, P, Pb, Sb, Sn, Ti, Tl, U, and Zn were compared to different contamination metrics and ecological risk assessment indices. The average concentrations were in the following decreasing order: Zn > > > Cr > > Cu > Ni > Pb > Co > As > Cd with mean (± SD) of 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1, 0.30 ± 0.09 mg kg-1, respectively, with strong indications of anthropogenic sources. Average concentrations were in the following decreasing order: Zn > > > Cr, Cu, Ni, Pb, Co, As, and Cd levels (mean ± SD) were 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1 and 0.30 ± 0.09 mg kg-1 with strong indications of anthropogenic sources. The geo-accumulation index (Igeo) and enrichment factor categorisation schemes, respectively, classified these as uncontaminated (level 0) and depletion to minimal enrichment (level 1), while the ecological risk analysis classified them as "low risk". The mouth of the Nyando River, as well as Kisumu, Kendu, and Homa bays, were the most element-enriched and should be prioritised for focused monitoring and remediation. As a result, targeted land management of urban, industrial, transportation, and agricultural areas offers the opportunity to reduce sediment inputs into the lake ecosystem.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Metals, Heavy/analysis , Ecosystem , Cadmium/analysis , Lakes , Kenya , Lead/analysis , Environmental Monitoring , Water Pollutants, Chemical/analysis , Geologic Sediments/analysis , Risk Assessment , China
2.
Environ Geochem Health ; 45(8): 6137-6162, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37266752

ABSTRACT

The impact of population expansion through economic growth and development has been identified as one of the key drivers of both water and sediment contamination from potentially harmful elements (PHEs). This presents a major hazard not only to aquatic ecosystems but local riparian communities and beyond who rely heavily on this natural resource for drinking water and fish-a valuable source of dietary micronutrients and protein. The present study measured biogeochemical concentration of PHEs in water, sediment and fish from locations pooled into four zones within Winam Gulf and Lake Victoria area of Kenya. Captured fish were used as a sentinel receptor of lake health to evaluate potential risks to fisheries and aquaculture food security. In water, concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu) and lead (Pb) were observed above the United States Environmental Protection Agency (US EPA) maximum contamination level drinking water guidelines (MCL), with aluminium (Al) observed above the Aquatic Life Criteria in all four zones. Similarly, sediment concentrations in all four zones exceeded the US EPA Effects range low (ERL) threshold guidelines for Cu, nickel (Ni), zinc (Zn) and Pb, with Cu, Zn and Pb classed at moderate contamination levels using the contamination factor. Fish tissue concentrations from the four zones were calculated using recommended daily intakes (RDI) and for PHEs as provisional maximum tolerable intakes (PMTIs) and indicated most macro- and micronutrients were at or below 10% RDI from aquaculture and wild fish, with Se indicating a greater RDI (16-29%) in all the zones. Contributions of PHEs to PMTIs were below threshold guidelines for both aquaculture and wild fish with only Cd, Cr and Pb levels being above the PMTI thresholds. There is a need to assess the long-term effects of persistent anthropogenic PHE input into Winam Gulf and the wider Lake Victoria basin. Continued monitoring of PHEs using both historical and more recent data will enable future management policies to be implemented through improved mitigation strategies to reduce their impact on water quality, fish health and subsequent human health.


Subject(s)
Drinking Water , Metals, Heavy , Water Pollutants, Chemical , Animals , Humans , Lakes , Cadmium , Environmental Monitoring , Kenya , Ecosystem , Lead , Water Pollutants, Chemical/analysis , Aquaculture , Fishes/metabolism , Micronutrients , Metals, Heavy/analysis , Risk Assessment
3.
Philos Trans R Soc Lond B Biol Sci ; 378(1881): 20220271, 2023 07 17.
Article in English | MEDLINE | ID: mdl-37246384

ABSTRACT

Africa is experiencing extensive biodiversity loss due to rapid changes in the environment, where natural resources constitute the main instrument for socioeconomic development and a mainstay source of livelihoods for an increasing population. Lack of data and information deficiency on biodiversity, but also budget constraints and insufficient financial and technical capacity, impede sound policy design and effective implementation of conservation and management measures. The problem is further exacerbated by the lack of harmonized indicators and databases to assess conservation needs and monitor biodiversity losses. We review challenges with biodiversity data (availability, quality, usability and database access) as a key limiting factor that impacts funding and governance. We also evaluate the drivers of both ecosystems change and biodiversity loss as a central piece of knowledge to develop and implement effective policies. While the continent focuses more on the latter, we argue that the two are complementary in shaping restoration and management solutions. We thus underscore the importance of establishing monitoring programmes focusing on biodiversity-ecosystem linkages in order to inform evidence-based decisions in ecosystem conservation and restoration in Africa. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.


Subject(s)
Conservation of Natural Resources , Ecosystem , Biodiversity , Africa
4.
BMC Microbiol ; 20(1): 107, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32357840

ABSTRACT

BACKGROUND: Footrot and interdigital dermatitis are endemic infectious diseases in all sheep farming regions, impairing welfare and production. The development of efficacious vaccines against the primary causative pathogen has been hampered by the extensive antigenic diversity of Dichelobacter nodosus. Understanding the heterogeneity of the pathogen within and between flocks is essential if the feasibility of bespoke vaccine production is to be assessed for use in the U.K. RESULTS: In this study 56 ewe and lamb isolates from 9 flocks were compared by D. nodosus serogroup and Multi Locus Sequence Type which provides significantly enhanced discriminatory power for molecular epidemiology. Serogroup heterogeneity between flocks ranged from two to five unique serogroups per flock. Three flocks contained isolates of two serogroups, two flocks contained isolates of three serogroups and one flock included isolates of five serogroups. Analysis of 25 isolates from one flock with high prevalence of lameness, identified that serogroup and sequence type was significantly correlated with age. Significantly higher proportion of lambs were infected with serogroup B (principally ST85) as opposed to serogroup H (principally ST86), which predominated amongst adult sheep. CONCLUSIONS: Genomic heterogeneity of the pathogen was significantly lower within flock compared to heterogenicity observed between flocks. Furthermore, this study indicates that within a flock, the host-pathogen dynamics and susceptibility to particular D. nodosus strains may be age dependent.


Subject(s)
Dichelobacter nodosus/classification , Genetic Heterogeneity , Gram-Negative Bacterial Infections/veterinary , Multilocus Sequence Typing/methods , Sheep Diseases/microbiology , Animals , Bacterial Typing Techniques , Dichelobacter nodosus/genetics , Dichelobacter nodosus/isolation & purification , Digital Dermatitis/microbiology , Female , Foot Rot/microbiology , Gram-Negative Bacterial Infections/microbiology , Phylogeny , Serogroup , Sheep , United Kingdom
5.
Sci Rep ; 4: 5431, 2014 Jun 25.
Article in English | MEDLINE | ID: mdl-24961164

ABSTRACT

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-ß1, IL-6 and/or IL-1ß. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4(+) and WC1(+) γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17(+) T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Interleukin-17/immunology , Membrane Glycoproteins/immunology , Neospora/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , Th17 Cells/immunology , Animals , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/parasitology , Cattle , Cells, Cultured , Chlorocebus aethiops , Coculture Techniques , Cytotoxicity, Immunologic/immunology , Fibroblasts/immunology , Fibroblasts/metabolism , Fibroblasts/parasitology , Host-Parasite Interactions/immunology , Interferon-gamma/immunology , Interferon-gamma/pharmacology , Interleukin-17/metabolism , Interleukin-6/immunology , Interleukin-6/pharmacology , Membrane Glycoproteins/metabolism , Neospora/physiology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Th17 Cells/drug effects , Th17 Cells/metabolism , Time Factors , Transforming Growth Factor beta1/immunology , Transforming Growth Factor beta1/pharmacology , Vero Cells
6.
Anim Genet ; 42(4): 341-53, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21749416

ABSTRACT

The chemokine system comprises a family of small chemoattractant molecules that have roles in both the healthy and diseased organism. Chemokines act by binding specific receptors on the target cell surface and inducing chemotaxis. The human chemokine system is well characterized, with approximately fifty chemokines identified that fall into four families. The chemokines and their receptors are promiscuous in that one chemokine can often bind several receptors, and vice versa. Study of the bovine chemokine system has been restricted to date to a handful of chemokines, and the identification of bovine chemokines is largely based on the closest human homologue. This method of identification is prone to error and may result in the misassumption of function of a particular chemokine. Here, we review current knowledge of bovine chemokines and reassess the bovine chemokine system based on phylogenetic and syntenic approaches. The bovine chemokine system, for the most part, shows high similarity to the chemokine system of other mammals such as humans; however, differences have been identified. Cattle possess fewer chemokines than humans, yet also possess chemokines that have no obvious homologue in the human system. These 'missing' and 'novel' chemokines may represent functional differences between the bovine and human chemokine systems that may affect the way in which these species are able to respond to specific pathogen repertoires.


Subject(s)
Chemokines/classification , Chemokines/genetics , Evolution, Molecular , Multigene Family/genetics , Phylogeny , Animals , Cattle , Chemokines/immunology , Chemokines/physiology , Humans , Species Specificity , Synteny/genetics
7.
Dev Comp Immunol ; 34(10): 1035-41, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20470819

ABSTRACT

Homology modelling is considered the most accurate technique for computational prediction of protein structure. However, this technique comes with fundamental caveats of dependency on template quality, identification of structural features and accuracy of alignment. Leucine-rich repeats (LRRs) characterise a diverse family of proteins. Recently resolved structures reveal a highly conserved region in LRRs that assemble into the curved parallel beta-sheet lining the inner circumference of their solenoid structure. Thus, prediction of these structurally important regions is essential in the comparative modelling of LRR proteins and their interactions. Here, we describe the generation of tLRRdb, a database of selected Toll-like receptor (TLR) sequences with annotated co-ordinates. Derived from this is LRRfinder, a web application for the identification of LRRs within user-defined sequences to facilitate identification of structurally important regions, particularly relevant for protein-protein interaction studies and classification of novel sequences. LRRfinder is available at: www.lrrfinder.com.


Subject(s)
Computational Biology/methods , Databases, Protein , Leucine/metabolism , Software , Toll-Like Receptors/metabolism , Algorithms , Animals , Computer Simulation , Humans , Leucine/chemistry , Protein Interaction Mapping , Protein Structure, Tertiary/genetics , Repetitive Sequences, Amino Acid/genetics , Toll-Like Receptors/chemistry
9.
Phys Med Biol ; 52(24): 7193-209, 2007 Dec 21.
Article in English | MEDLINE | ID: mdl-18065834

ABSTRACT

Increasing use by law enforcement agencies of the M26 and X26 TASER electrical incapacitation devices has raised concerns about the arrhythmogenic potential of these weapons. Using a numerical phantom constructed from medical images of the human body in which the material properties of the tissues are represented, computational electromagnetic modelling has been used to predict the currents arising at the heart following injection of M26 and X26 waveforms at the anterior surface of the chest (with one TASER 'barb' directly overlying the ventricles). The modelling indicated that the peak absolute current densities at the ventricles were 0.66 and 0.11 mA mm(-2) for the M26 and X26 waveforms, respectively. When applied during the vulnerable period to the ventricular epicardial surface of guinea-pig isolated hearts, the M26 and X26 waveforms induced ectopic beats, but only at current densities greater than 60-fold those predicted by the modelling. When applied to the ventricles in trains designed to mimic the discharge patterns of the TASER devices, neither waveform induced ventricular fibrillation at peak currents >70-fold (for the M26 waveform) and >240-fold (for the X26) higher than the modelled current densities. This study provides evidence for a lack of arrhythmogenic action of the M26 and X26 TASER devices.


Subject(s)
Arrhythmias, Cardiac/etiology , Electric Stimulation/adverse effects , Electric Stimulation/instrumentation , Electromagnetic Phenomena/methods , Models, Cardiovascular , Weapons , Animals , Arrhythmias, Cardiac/physiopathology , Computer Simulation , Electric Conductivity , Electric Injuries/etiology , Electric Injuries/physiopathology , Electrocardiography , Electroshock , Finite Element Analysis , Guinea Pigs , Heart Conduction System , Heart Ventricles/injuries , Heart Ventricles/physiopathology , Humans , In Vitro Techniques , Law Enforcement , Phantoms, Imaging
10.
Vet Immunol Immunopathol ; 114(1-2): 25-36, 2006 Nov 15.
Article in English | MEDLINE | ID: mdl-16904754

ABSTRACT

Protection against tuberculosis (TB) is associated with Th1-type cell-mediated immunity (CMI). Whilst the intradermal injection of partially purified derivatives of tuberculin (PPD) represents the classic test assessing the delayed type hypersensitivity (DTH) response used in both humans and cattle for diagnosing TB, it has been suggested that the test may modulate host CMI responses. To investigate the kinetics of the development of the DTH response and its subsequent effect on CMI responses, groups of 6-month old calves were inoculated intranasally with 8 x 10(4) cfu of Mycobacterium bovis, subjected to the comparative intradermal tuberculin test (TT) using bovine and avian PPD (PPD-B, PPD-A) at various time intervals post-infection, and immune responses compared. These included DTH, lymphocyte proliferation, IgG production, and synthesis of the cytokines: IFNgamma, IL-10, IL-4, IL-6, and IL-13. All animals were subjected to post-mortem examination. The kinetics of the development of the DTH response assessed in the TT was such that infected cattle could be identified as early as 3 weeks post-infection, which correlated with the detection of an antigen-specific IFNgamma response. Transient increases in plasma-derived IFNgamma as a result of TT during an established TB infection were more pronounced when blood was stimulated with PPD-A compared with PPD-B stimulation. This has the potential to mask diagnosis of infection as a result of the stronger avian-bias if the IFNgamma test is used the week following TT. Disease pathology was not affected by TT. A transient failure to a second TT was observed in 1 of 30 animals and the time (post-infection) at which the TT is administered may be of significance. In serum, IgG responses to PPD-B, which were undetectable prior to TT, were elevated after TT and were most pronounced in cattle that were TT at 6 weeks post-infection. Other cytokines were also affected by the TT; IL-4 mRNA levels increased and IL-6 mRNA levels decreased, whilst PPD-B specific IL-10 protein synthesis was enhanced. These observations may offer the potential for further diagnostic assays that could complement the TT and IFNgamma test.


Subject(s)
Immunity, Cellular/immunology , Mycobacterium bovis/immunology , Tuberculin Test/veterinary , Tuberculosis, Bovine/immunology , Animals , Cattle , Cytokines/genetics , Cytokines/immunology , Histocytochemistry , Hypersensitivity, Delayed/immunology , Hypersensitivity, Delayed/microbiology , Hypersensitivity, Delayed/veterinary , Immunoglobulin G/blood , Kinetics , Male , Mycobacterium bovis/isolation & purification , RNA, Messenger/chemistry , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Tuberculin Test/methods , Tuberculosis, Bovine/diagnosis , Tuberculosis, Bovine/microbiology , Tuberculosis, Bovine/pathology
11.
Vet Immunol Immunopathol ; 113(1-2): 234-42, 2006 Sep 15.
Article in English | MEDLINE | ID: mdl-16797084

ABSTRACT

C-type lectin receptors (CTLR) are cell-surface signalling molecules that recognize a range of highly conserved pathogen molecules and instigate the appropriate immune response. Here, we report the cloning, sequencing, mapping and expression pattern of the bovine C-type lectin domain family 7, member A (CLEC7A; synonyms CLCSF12, Dectin-1). We identified two isoforms, similar to the human system, with a long and short neck. Overall, the organization of the two bovine CLEC7A genes is similar to that of humans and mice. The CLEC7A gene maps on Bos taurus chromosome 5 (BTA5). mRNA transcripts for CLEC7A were detected in bone-marrow cells, monocytes, macrophages and dendritic cells and NK cells, but not in CD4(+) T-cells or CD21(+) B-cells. The increased knowledge of the genomic organization of the bovine CTLR genes may promote our understanding of their evolution and help in the identification of bovine genes underlying disease-resistance traits.


Subject(s)
Cattle/immunology , Membrane Proteins/genetics , Membrane Proteins/immunology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/immunology , Amino Acid Sequence , Animals , Base Sequence , Cattle/genetics , Chromosome Mapping/veterinary , Cloning, Molecular , Female , Lectins, C-Type , Membrane Proteins/biosynthesis , Molecular Sequence Data , Nerve Tissue Proteins/biosynthesis , Protein Isoforms , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Sequence Alignment , Sequence Analysis, DNA
12.
Clin Exp Immunol ; 144(2): 281-9, 2006 May.
Article in English | MEDLINE | ID: mdl-16634802

ABSTRACT

Cytokine expression in lymph nodes from cattle inoculated intranasally with Mycobacterium bovis was compared to that of non-infected animals using real-time polymerase chain reaction. The effect of M. bovis infection, 4 months post-challenge, was to suppress the expression of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as the pro-inflammatory cytokines tumour necrosis factor (TNF) and IL-6. Expression of interferon (IFN)-gamma and IL-12 was maintained. Animals vaccinated with bacille Calmette-Guérin responded differently to challenge with M. bovis. In particular, no decrease in expression of IL-4 or IL-6 was observed following challenge of vaccinated animals and decreased IFN-gamma was detected. Also, vaccinated animals had higher levels of IL-4 and IL-10 transcripts compared to unvaccinated animals following challenge. These changes in cytokine expression levels led to a significant shift in the IFN-gamma/IL-4 or IFN-gamma/IL-10 ratio within the lymph node following challenge. Challenged animals generally showed a strong Th1 bias that was not seen in animals vaccinated prior to challenge. An inverse correlation between the level of pathology and bacterial load within the lymph node and the expression of IL-4, IL-10 and TNF was also observed. These results suggest that in the lymph nodes of cattle with established tuberculosis and a persisting bacterial infection, maintenance of the pro-inflammatory response in combination with a suppressed anti-inflammatory response may control the infection but contribute to host-induced tissue damage. Vaccination, which reduces the bacterial load and consequently the IFN-gamma response, may result in less suppression of anti-inflammatory cytokines.


Subject(s)
BCG Vaccine/therapeutic use , Cytokines/immunology , Lymph Nodes/immunology , Tuberculosis, Bovine/immunology , Animals , Cattle , Gene Expression , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-4/immunology , Interleukin-6/immunology , Lymph Nodes/pathology , Th1 Cells/immunology , Tuberculosis, Bovine/pathology , Tumor Necrosis Factor-alpha/immunology
14.
Microb Drug Resist ; 4(1): 51-5, 1998.
Article in English | MEDLINE | ID: mdl-9533725

ABSTRACT

Multiply-antibiotic-resistant isolates of serogroup 19 Streptococcus pneumoniae, possessing altered penicillin-binding protein (PBP) 1A, 2B, and 2X genes that are indistinguishable from those of the Spanish multiresistant serogroup 23F clone, are now commonly encountered in Spain. Those isolates that have been serotyped express type 19F capsular polysaccharide. Serotyping of further isolates, and hybridization using a serotype 19F-specific probe, has shown that some of them are serotype 19A, rather than 19F. The Spanish multiresistant serotype 19A, 19F, and 23F multiresistant strains were all shown to be very closely related in overall genotype, as they were indistinguishable by REP-PCR and by the sequencing of internal fragments of three house-keeping genes. The serotype 19A multiresistant strains, like the serotype 19F multiresistant strains, therefore appear to be a serotype variant of the Spanish multiresistant serotype 23F clone, which presumably has arisen by recombination at the capsular locus.


Subject(s)
Bacterial Proteins , Drug Resistance, Microbial/genetics , Drug Resistance, Multiple/genetics , Hexosyltransferases , Peptidyl Transferases , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/genetics , Bacterial Capsules/genetics , Carrier Proteins/genetics , DNA Fingerprinting , Genes, Bacterial , Genetic Variation , Humans , Molecular Epidemiology , Muramoylpentapeptide Carboxypeptidase/genetics , Penicillin-Binding Proteins , Pneumococcal Infections/epidemiology , Pneumococcal Infections/microbiology , Polymerase Chain Reaction , Serotyping , Spain/epidemiology , Species Specificity , Streptococcus pneumoniae/drug effects
15.
Mol Microbiol ; 27(1): 73-83, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9466257

ABSTRACT

Serotype 19F variants of the major Spanish multiresistant serotype 23F clone of Streptococcus pneumoniae have been proposed to have arisen by recombinational exchanges at the capsular biosynthetic locus. Members of the Spanish multiresistant serotype 23F clone and the serotype 19F variants were confirmed to be essentially identical in overall genotype, as they were indistinguishable by REP-PCR, and had identical sequences at three polymorphic housekeeping genes. Eight serotype 19F variants were studied and all had large recombinational replacements at the capsular biosynthetic locus. In all cases, one of the recombinational cross-over points appeared to be upstream of dexB, which flanks one end of the capsular locus, and in six of the variants the other cross-over point was downstream of aliA, which flanks the other end of the locus. In two strains a recombinational cross-over point between the introduced serotype 19F capsular region and that of the Spanish serotype 23F clone could be clearly identified, within cpsN in one strain and within cpsM in the other. The differences in the recombinational junctions and sequence polymorphisms within the introduced capsular genes, suggested that the eight serotype 19F variants emerged on at least four separate occasions. Changes in capsular type by recombination may therefore be relatively frequent in pneumococci and this has implications for the long-term efficacy of conjugate pneumococcal vaccines that will protect against only a limited number of serotypes.


Subject(s)
Drug Resistance, Multiple/physiology , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/genetics , Recombination, Genetic/physiology , Streptococcus pneumoniae/chemistry , Streptococcus pneumoniae/genetics , Base Sequence , Crossing Over, Genetic , DNA Fingerprinting , DNA, Bacterial/chemistry , Molecular Sequence Data , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polysaccharides, Bacterial/biosynthesis , Repetitive Sequences, Nucleic Acid , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Serotyping , Spain , Streptococcus pneumoniae/classification
16.
Methods Mol Med ; 15: 537-53, 1998.
Article in English | MEDLINE | ID: mdl-21390765

ABSTRACT

The widespread use, or perhaps overuse, of penicillin during the past 50 yr has driven the evolution of resistance to penicilling in numerous different species of bacteria.Typically, resistance has arisen as a result of the acquisition of ß-lactamases that inactivate the antibiotic (see Chapter 25 . Alternatively, in some Gram-negative bacteria, resistance may have arisen by a reduction in the ability of the antibiotic to access its target. However, in a number of clinically important Gram-negative and Gram-positive bacteria, resistance has arisen by alteration of the targets for penicillin and other ß-lactam antibiotics, namely, the penicillin-binding proteins (PBPs).

17.
J Infect Dis ; 174(4): 884-8, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8843237

ABSTRACT

Previous studies have suggested that relatively penicillin-resistant (RPR) capsular group 9L strains in western Canada may be clonally related. To test this hypothesis, restriction fragment length polymorphisms (RFLPs) were examined using DNA probes for pspA and a newly recognized pneumococcal genetic element, IS1167. Penicillin-binding proteins (PBPs) and PBP genes from representative strains were also studied. All RPR type 9L strains demonstrated an identical RFLP when probed with IS1167, and 12 of 14 RPR strains had the same RFLP when examined with pspA. Amplification of pspA by polymerase chain reaction and restriction endonuclease digestion showed that the 9L strains had common DNA fragments not identified in any of the penicillin-susceptible strains. The 9L strains apparently have a low-affinity PBP 2B distinct from those of other capsular types. These data derived from new genetic markers and PBP analysis strongly support a clonal origin of RPR type 9L pneumococci of western Canada.


Subject(s)
Bacterial Proteins/genetics , Carrier Proteins/analysis , DNA, Bacterial/analysis , Heat-Shock Proteins/genetics , Hexosyltransferases , Muramoylpentapeptide Carboxypeptidase/analysis , Penicillin Resistance , Peptidyl Transferases , Streptococcus pneumoniae/drug effects , Carrier Proteins/genetics , Humans , Muramoylpentapeptide Carboxypeptidase/genetics , Penicillin-Binding Proteins , Polymorphism, Restriction Fragment Length , Streptococcus pneumoniae/chemistry , Streptococcus pneumoniae/genetics
18.
Microb Pathog ; 21(4): 265-75, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8905615

ABSTRACT

Pneumococcal surface protein A (PspA) has been shown to be a serologically variable virulence factor of Streptococcus pneumoniae. In mice, PspA can elicit antibodies capable of protecting them against otherwise fatal infections with encapsulated pneumococci. In previous studies it has been reported that almost all isolates have two apparently unlinked genomic sequences that are highly homologous to the 5' and 3' halves of Rx1 pspA, although out MAbs to PspA have not detected more than one PspA in any given isolate of S. Pneumoniae. Recently, we have identified four isolates from a clone of capsular serotype 6B pneumococci (MC25-28) that simultaneously express two distinct PspAs. Each of the isolates (MC25-28) exhibited the same two Kpn I fragments (each containing a Hind III site) that hybridized with Rx1 pspA. MAbs specific for PspA detected two PspAs characterized by different molecular weights and different serologic patterns of reactivity (PspA type 6 detected by MAbs XiR278 and 2A4, and PspA type 34 detected only by MAb 7D2) in each of the four isolates. In previous studies XiR278 and 2A4 frequently have been observed to react with PspA epitopes of the same strain. Based on molecular weight data both epitopes were always present on the same molecule. Our present findings raise the possibility that pneumococci make a second serologically variable PspA which is generally not detected by currently available MAbs to PspA.


Subject(s)
Antigens, Bacterial/genetics , Bacterial Capsules/genetics , Bacterial Proteins/genetics , Streptococcus pneumoniae/genetics , Bacterial Proteins/biosynthesis , DNA Fingerprinting , Gene Dosage , Genes, Bacterial , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Serotyping , Streptococcus pneumoniae/classification
19.
Microbiology (Reading) ; 142 ( Pt 10): 2747-57, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8885390

ABSTRACT

We analysed a collection of 95 multiply antibiotic-resistant pneumococci, recovered since 1988 from 14 Spanish hospitals, that have MICs > or = 0.25 microgram benzylpenicillin ml-1. The majority of the isolates were of serogroups 14, 23, 6, 19 and 15, which are currently the serogroups mainly associated with multiresistance in Spain. All of the serogroup 23 isolates were members of the major Spanish serotype 23F multiresistant clone. Similarly, most of the serogroup 6 isolates were members of the major multiresistant serotype 6B clone, or variants of this clone. Eighteen of the 24 isolates of serogroup 19 were members of a highly penicillin-resistant clone that appears to be a serotype 19F variant of the major Spanish serotype 23F multiresistant clone. Eighteen of the 25 isolates of serotype 14 were members of a previously uncharacterized highly penicillin-resistant clone. Thirteen of the 16 isolates of serogroup 15 were members of a single previously unreported clone of serotype 15F that had moderate levels of resistance to penicillin. Approximately 65% of the multiresistant pneumococci that are currently circulating in Spain were members of the three new clones of serotype 14, 15F and 19F that we describe here, or the previously described serotype 6B and 23F clones. The other 35% of isolates were minor variants of the major clones, unrelated minor clones, and unique isolates, many of which appeared to have arisen by horizontal gene transfer events.


Subject(s)
Bacterial Proteins , DNA Fingerprinting , Drug Resistance, Multiple/genetics , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/genetics , Carrier Proteins/genetics , Chloramphenicol Resistance , Genes, Bacterial/genetics , Hexosyltransferases/genetics , Hospitals , Humans , Molecular Epidemiology , Multienzyme Complexes/genetics , Muramoylpentapeptide Carboxypeptidase/genetics , Penicillin Resistance/genetics , Penicillin-Binding Proteins , Peptidyl Transferases/genetics , Pneumococcal Infections/epidemiology , Sequence Analysis, DNA , Serotyping , Spain/epidemiology , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/enzymology , Streptococcus pneumoniae/isolation & purification , Tetracycline Resistance
20.
Antimicrob Agents Chemother ; 39(6): 1306-13, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7574521

ABSTRACT

Streptococcus pneumoniae CS109 and CS111 were isolated in the United States in 1991 and have high levels of resistance to expanded-spectrum cephalosporins (MICs of 8 and 32 micrograms of cefotaxime per ml, respectively). CS109, but not CS111, also showed high-level resistance to penicillin. As both strains expressed the serotype 23F capsule, were very closely related in overall genotype, and possessed identical or closely related mosaic pbp1a, pbp2x, and pbp2b genes, it is likely that they have arisen from a recent common ancestor. High-level resistance to expanded-spectrum cephalosporins was entirely due to alterations of penicillin-binding proteins (PBPs) 1a and 2x, since a mixture of the cloned pbp1a and pbp2x genes from the resistant strains could transform the susceptible strain R6 to the full level of cephalosporin resistance of the clinical isolates. Both PBP1a and PBP2x of these strains were more resistant to inhibition by cephalosporins than those of typical highly penicillin-resistant isolates. The pbp1a genes of CS109 and CS111 were identical in sequence, and the fourfold difference in their levels of resistance to cephalosporins was due to a Thr-550-->Ala substitution at the residue following the conserved Lys-Ser-Gly motif of PBP2x. This substitution was also the major cause of the 16-fold-lower resistance of CS111 to penicillin. The pbp2x gene of CS111, in an appropriate genetic background, could provide resistance to 16 micrograms of cefotaxime per ml but only to 0.12 microgram of benzylpenicillin per ml. Removal of the codon 550 mutation resulted in a pbp2x gene that provided resistance to 4 microgram of cefotaxime per ml and 4 microgram of benzylpenicillin per ml. The Thr-550-->Ala substitution in CS111 therefore appears to provide increased resistance to expanded-spectrum cephalosporins but a loss of resistance to penicillin.


Subject(s)
Cephalosporin Resistance/genetics , Cephalosporins/pharmacology , DNA, Bacterial/chemistry , Streptococcus pneumoniae/genetics , Amino Acid Sequence , Base Sequence , Cefotaxime/pharmacology , Ceftriaxone/pharmacology , DNA Fingerprinting , Humans , Microbial Sensitivity Tests , Molecular Sequence Data , Mosaicism , Mutagenesis, Site-Directed , Penicillin G/pharmacology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purification , Transformation, Bacterial
SELECTION OF CITATIONS
SEARCH DETAIL
...