SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The remarkable structural diversity of glycans in nature, and their roles in cellular processes, host-pathogen interactions, biological diversity and speciation can be explained by evolutionary processes.
Escherichia coli represents a versatile and diverse enterobacterial species which can be subdivided into (i) nonpathogenic, commensal, (ii) intestinal pathogenic and (iii) extraintestinal pathogenic strains. This classification is mainly based on the presence or absence of DNA regions which are frequently associated with certain pathotypes. In most cases, this genetic information has been horizontally acquired and belongs to the flexible E. coli genome, such as plasmids, bacteriophages and genomic islands. These genomic regions contribute to the rapid evolution of E. coli variants as they are frequently subject to rearrangements, excision and transfer as well as further acquisition of additional DNA thus contributing to the creation of new (pathogenic) variants. Genetic diversity and genome plasticity of E. coli has been underestimated. The accumulating amount of sequence information generated in the era of "genomics" helps to increase our understanding of factors and mechanisms that are involved in diversification of this bacterial species as well as in those that may direct host specificity.
Oilseed rape (Brassica napus) is one of the major oilseed crops in the world but is vulnerable to attack by many pathogens and insect pests. In addition to the host plant genotype, micro-organisms present in the rhizosphere and within plant tissues affect the susceptibility to plant pathogens. While rapid progress has been achieved concerning the concept of plant resistance genes, information on the role of the microbial community in plant protection is less apparent. We have studied the endophytic bacterial populations present in different tissues of oilseed rape and also analysed several cultivars (Express, Libraska, Maluka and Westar), which differ in their susceptibility to the wilt pathogen Verticillium longisporum. The population diversity was studied using agar plating assay, fatty acid methyl ester analysis and functional characterisation of isolated strains. Our work shows that already in the seeds there exists diversity in populations as well as in the total microbial load between two of the four tested cultivars. About 50% of the strains isolated from cultivars Express and Libraska showed moderate to strong direct inhibition of V. longisporum. The diversity of the endophytic flora isolated from oilseed rape and its implications in crop protection are discussed.
Entamoeba histolytica, the premier intestinal protozoan, has traversed time in its relentless quest for survival in its dichotomous role of parasite and pathogen. Enigmatic in its transition from human intestinal commensal to invader of human tissue, diverse in its pathogenicity for the human host, and intricate in its bacterial interrelationship in the bowel, E. histolytica has become the focal point of intensive investigation in its basic biology underscoring human pathogenicity. This review will focus on facets of cell biology, pathophysiology, clinical, therapeutic, and epidemiologic, correlates, along with diagnostic modalities and future research trends.
The inhalation of conidia of Blastomyces dermatitidis, a fungus found in soil, causes disease in humans and animals. We studied the genetic diversity of this pathogen by extracting DNA yeasts and analyzing them with a polymerase chain reaction (PCR)-based typing system we developed, which used restriction fragment analysis of amplicons from the regions between the rDNA repeats and allowed us to class isolates into 3 major groups. Strains were further differentiated by use of PCR fingerprinting with 3 different primers. Fifty-nine isolates collected over 35 years from 15 regions (United States, India, Africa, Canada) were analyzed. Genotypic groups A, B, and C contained 17, 23, and 19 isolates, which were divided into 5, 15, and 12 types, respectively. All 16 isolates from North America in group A were from the upper midwestern United States or Canada, whereas 0 of 20 isolates from the southeastern United States were in group A. Studies of the largest collection from 1 locale (Eagle River, WI), revealed that the soil isolates studied were not responsible for the majority of cases in this outbreak, as previously proposed, and that >1 strain was present in the environment and in patients. Overall, these results provide a tool for the epidemiological study of blastomycosis and illuminate the genetic and geographic diversity of this important pathogen.
Rhesus macaques immunized with simian immunodeficiency virus SIVmac239Deltanef but not protected from SIVmac251 challenge were studied to determine the genetic and biological characteristics of the breakthrough viruses. Assessment of SIV genetic diversity (env V1-V2) revealed a reduction in the number of viral species in the immunized, unprotected macaques, compared to the number in nonimmunized controls. However, no evidence for selection of a specific V1-V2 genotype was observed, and biologically cloned isolates from the animals with breakthrough virus were similar with respect to replication kinetics and coreceptor use in vitro.
The opportunistic fungal pathogens Candida inconspicua and C. norvegensis are very rarely isolated from patients and are resistant to fluconazole. We collected 38 strains of the two microorganisms isolated from Europe and Japan, and compared the polymorphism of the rRNA intergenic spacer (IGS) and internal transcribed spacer (ITS) regions, antifungal drug susceptibility, and extracellular enzyme production as a potential virulence factor. While the IGS sequences of C. norvegensis were not very divergent (more than 96.7% sequence similarity among the strains), those of C. inconspicua showed remarkable diversity, and were divided into four genotypes with three subtypes. In the ITS region, no variation was found in either species. Since the sequence similarity of the two species is approximately 70% at the ITS region, they are closely related phylogenetically. Fluconazole resistance was reconfirmed for the two microorganisms but they were susceptible to micafungin and amphotericin B. No strain of either species secreted aspartyl proteinase or phospholipase B. These results provide basal information for accurate identification, which is of benefit to global molecular epidemiological studies and facilitates our understanding of the medical mycological characteristics of C. inconspicua and C. norvegensis.
The destructive late blight pathogen Phytophthora infestans is notorious for its rapid adaptation to circumvent detection mediated by plant resistance (R) genes. We performed comparative genomic hybridization on microarrays (array-CGH) in a near genome-wide survey to identify genome rearrangements related to changes in virulence. Six loci with copy number variation were found, one of which involves an amplification colocalizing with a previously identified locus that confers avirulence in combination with either R gene R3b, R10, or R11. Besides array-CGH, we used three independent approaches to find candidate genes at the Avr3b-Avr10-Avr11 locus: positional cloning, cDNA-AFLP analysis, and Affymetrix array expression profiling. This resulted in one candidate, pi3.4, that encodes a protein of 1956 amino acids with regulatory domains characteristic for transcription factors. Amplification is restricted to the 3' end of the full-length gene but the amplified copies still contain the hallmarks of a regulatory protein. Sequence comparison showed that the amplification may generate modular diversity and assist in the assembly of novel full-length genes via unequal crossing-over. Analyses of P. infestans field isolates revealed that the pi3.4 amplification correlates with avirulence; isolates virulent on R3b, R10, and R11 plants lack the amplified gene cluster. The ancestral state of 3.4 in the Phytophthora lineage is a full-length, single-copy gene. In P. infestans, however, pi3.4 is a dynamic gene that is amplified and has moved to other locations. Modular diversity could be a novel mechanism for pathogens to quickly adapt to changes in the environment.
BACKGROUND & AIMS: Specific regions of the cag pathogenicity island (PAI) believed to enhance the virulence of Helicobacter pylori, as well as vacuolating cytotoxin gene alleles and IS605 inserts, were investigated to define diversity within infecting strain populations from patients with peptic ulcer disease and from healthy individuals. METHODS: The H. pylori studied comprised 67 isolates from 26 subjects and 14 reference strains. Specific polymerase chain reaction assays were used to test for cagA and picB in the cagI region, the virD4 homologue in the cagII region, IS605 in the genome and in the cag PAI, the "empty site" indicating absence of the cag PAI, and different vacA gene alleles. RESULTS: Most (89%) subjects were infected by H. pylori with a contiguous cag PAI. No intermediate forms were found. IS605 was not detected within the cag PAI of any strain but was present elsewhere in the genomes of strains from 62% of subjects. Twenty individuals were infected with genotypically conserved populations of H. pylori. Six subjects had mixed infections, and in 3 of these cag(+)/cag(-) variants were present. CONCLUSIONS: The cag PAI-positive H. pylori was a feature of most infected individuals, irrespective of severity of associated disease. Combined genotyping showed that 8 individuals (31%) had mixed infections, which suggests that strain population structure may be an additional contributing factor in disease development.
Several attempts have been made at the removal of specific pathogens from the intestinal microflora using either bacteriophages or "predatory" bacteria such as Bdellovibrio spp. To date these attempts have had mixed success. A mechanism explaining these findings based on competitive hindrance by non-prey, or decoy species is put forward. It is shown that this hindrance tends to damp out predator-prey oscillations, and therefore reduces the probability of prey extinction. Possible experiments to verify this theory are discussed. The decoy effect may play a role in any system with high densities of bacteria or other particulate matter, such as activated sludge or biofilms.
Uncovering the correct phylogeny of closely related species requires analysis of multiple gene genealogies or, alternatively, genealogies inferred from the multiple alleles found at highly polymorphic loci, such as microsatellites. However, a concern in using microsatellites is that constraints on allele sizes may occur, resulting in homoplasious distributions of alleles, leading to incorrect phylogenies. Seven microsatellites from the pathogenic fungus Coccidioides immitis were sequenced for 20 clinical isolates chosen to represent the known genetic diversity of the pathogen. An organismal phylogeny for C. immitis was inferred from microsatellite-flanking sequence polymorphisms and other restriction fragment length polymorphism-containing loci. Two microsatellite genetic distances were then used to determine phylogenies for C. immitis, and the trees found by these three methods were compared. Congruence between the organismal and microsatellite phylogenies occurred when microsatellite distances were based on simple allele frequency data. However, complex mutation events at some loci made distances based on stepwise mutation models unreliable. Estimates of times of divergence for the two species of C. immitis based on microsatellites were significantly lower than those calculated from flanking sequence, most likely due to constraints on microsatellite allele sizes. Flanking-sequence insertions/deletions significantly decreased the accuracy of genealogical information inferred from microsatellite loci and caused interspecific length homoplasies at one of the seven loci. Our analysis shows that microsatellites are useful phylogenetic markers, although care should be taken to choose loci with appropriate flanking sequences when they are intended for use in evolutionary studies.
Genes of the major histocompatibility complex (MHC) play a critical role in immune recognition and are the most genetically diverse loci known. One hypothesis to explain this diversity postulates that pathogens adapt to common MHC haplotypes and thus favour selection of new or rare alleles. To determine whether the pathogenic yeast Cryptococcus neoformans adapts to MHC-dependent immune responses, it was serially passaged in two independent replicate lines of five B10 MHC-congenic strains and Balb/c mice. All passaged lines increased in virulence as measured by reduced host survival. MHC influenced the rate (trajectory) of virulence increase during passages as measured by significant differences in mortality rate (p < 0.001). However, when the post-passage strains were tested, no MHC differences in mortality rate remained and only minor differences in titres were observed. Also contrary to expectations, increased virulence in three lines passaged in B10 mice had a larger effect in Balb/c mice, and the evolution of virulence in lines passaged in alternating hosts was not retarded. To our knowledge, these data represent the first experimental test of MHC-specific adaptation in a non-viral pathogen. The failure to observe MHC effects despite dramatically increased virulence and host-genotype-specific adaptation to non-MHC genes suggests that escape of MHC-dependent immune recognition may be difficult for pathogens with unlimited epitopes or that other virulence factors can swamp MHC effects.
Pathogens that infect multiple hosts are commonly transmitted by vectors, and their transmission rate is often thought to depend on the proportion of hosts or vectors infected (i.e., frequency dependence). A model of a two-host, one-pathogen system with frequency-dependent transmission is used to investigate how sharing a pathogen with an alternative host influences pathogen-mediated extinction. The results show that if there is frequency-dependent transmission, a host can be rescued from pathogen-mediated extinction by the presence of a second host with which it shares a pathogen. The study provides an important conceptual counterexample to the idea that shared pathogens necessarily result in apparent competition by showing that shared pathogens can mediate apparent mutualism. We distinguish two types of dilution effect (pathogen reduction with increasing host diversity), each resulting from different underlying pathogen transmission processes and host density effects. These results have important consequences for understanding the role of pathogens in species interactions and in maintaining host species diversity.
The pathogenicity of Blastocystis hominis is extensively debated in the medical literature. Therefore, we did a prevalence study to investigate the association between the presence of several intestinal parasites and gastrointestinal symptoms in diverse patient cohorts. The study population consisted of 1216 adults, including immunocompromised patients, institutionalized psychiatric or elder subjects, immigrants from developing countries, travellers to developing tropical countries and controls. Several variables for each risk group were considered. Stools specimens, collected in triplicate, were processed by the same technicians. Clinical data about each subject were provided by standardized questionnaires. The presence of gastrointestinal symptoms were related to the presence of any parasite. In addition, on the basis of microbiological results, five subgroups of subjects were evaluated. The results showed a high prevalence of parasites in all the risk groups. Immunocompromised status, recent arrival from developing countries and the presence of behavioural aberrations were significantly related to presence of parasites. B. hominis was the parasite most frequently detected in each studied group. B. hominis showed a significant correlation with gastrointestinal symptoms only when detected in the group including subjects with a severe immunodepression. Immunodepression seems to be a factor of primary importance of the pathogenic role of B. hominis.
OBJECTIVE: To study microbial and susceptibility patterns and antimicrobial treatment responses in patients with severe, acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. DESIGN: Microbial investigation using tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage, as well as paired serologies. Evaluation of antimicrobial treatment by results of the initial investigation, susceptibility testing, and a repeated microbial investigation (tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage) after 72 hrs. SETTING: A respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS: Fifty severely exacerbated and mechanically ventilated patients with chronic obstructive pulmonary disease. INTERVENTIONS: Initial empirical antimicrobial treatment according to clinical judgment. MEASUREMENTS AND MAIN RESULTS: Overall, 36 of 50 patients (72%) had evidence of a microbial origin. Community-acquired endogenous pathogens were present in 70% of patients, and Gram-negative enteric bacilli and Pseudomonas/Stenotrophomonas species were present in 30%. All five isolates of Streptococcus pneumoniae were resistant to penicillin (three intermediately and two highly), and three were resistant to multiple antibiotics. Pseudomonas species revealed multiresistance in four of nine isolates (44%), and Stenotrophomonas maltophilia revealed multiresistance in one of two isolates. Antimicrobial treatment was modified according to diagnostic results in 11 of 31 patients (36%) with potentially pathogenic microorganisms. In patients who underwent a repeat investigation after 72 hrs, 24% of the initially present and potentially pathogenic microorganisms persisted. Inappropriate initial antimicrobial therapy was associated significantly with bacterial persistence (p < .002). CONCLUSIONS: Considering the diversity of microbial pathogens and the resistance rates especially to S. pneumoniae in this patient population, antimicrobial treatment should be based on the constant study of local microbial and susceptibility patterns along with routine microbial investigation of the individual patient.
The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.
The diversity and vertical transmission of double-stranded (ds) RNA in Helicobasidium mompa and Rosellinia necatrix was examined by electrophoresis and Northern hybridization. These two fungi share the similar niche as root rot pathogens of trees in forests and orchards, and had diverse dsRNAs. The detection frequency of dsRNA in both fungi was different; in H. mompa, 68.4% (132 out of 193 MCGs; mycelial compatibility groups) had dsRNA, whereas 20.9% (53 out of 254 MCGs) in R. necatrix. dsRNA banding patterns and Northern blot analyses revealed the presence of various dsRNA elements in both fungi. Hyphal tip isolation was mostly unsuccessful to remove dsRNA with some exceptions. Sexual reproduction functioned to remove dsRNA in both fungi since dsRNA was not detected from single sexual spore cultures. Possible explanations for the difference in the detection frequency of dsRNA are discussed in terms of the differences in their sexual reproduction and other factors.
Programmed cell death (apoptosis) is an important regulator of the host's response during infection with a variety of intracellular protozoan parasites. Parasitic pathogens have evolved diverse strategies to induce or inhibit host-cell apoptosis, thereby modulating the host's immune response, aiding dissemination within the host or facilitating intracellular survival. Here, we review the molecular and cell-biological mechanisms of the pathogen-induced modulation of host-cell apoptosis and its effects on the parasite-host interaction and the pathogenesis of parasitic diseases. We also discuss the previously unrecognized phenomenon of apoptotic cell death in (unicellular) protozoan parasites and its potential implications.