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At least 1,315 records · Page 73Linked to original sources
PubMed2006

Genetic interactions between the parasitoid wasp Leptopilina boulardi and its Drosophila hosts.

Coevolutionary arms races between hosts and parasites would not occur without genetic variation for traits involved in the outcome of parasitism. Genetic variations in resistance and virulence have only rarely been described in pairwise host-parasitoid interactions and have never been analysed in multi-species interactions, in contrast to well-characterized plant-pathogen interactions. This paper reports genetic variation in resistance of Drosophila yakuba to the parasitoid wasp Leptopilina boulardi. The genetic basis and geographic distribution of resistance is analysed. On the basis of these and previous findings, we demonstrate that there are different resistance patterns to the parasitoid species L. boulardi in D. melanogaster and D. yakuba, as well as different specificity levels in the parasitoid species, suggesting complex ecological interactions in the field. This first description of resistance-virulence genetic interactions between a parasitoid and its two host species provides empirical data showing that multi-species interactions may greatly influence coevolutionary processes.

Animals↗
PubMed2000

PCR detection of host and HIV-1 sequences from archival brain tissue.

Mutations in CCR5 and CCR2b have been recently shown to affect disease progression towards AIDS. A role for these host genotypes in AIDS dementia complex (ADC) has also been postulated but remains unclear. Additionally, brain-derived envelope sequences from HIV-1 have been associated with ADC but their specific contribution to pathogenesis remains uncertain. This study demonstrates the successful use of PCR techniques to isolate host CCR5 and CCR2b, and HIV-1 V3 sequences from paraffin embedded tissues from patients with and without ADC. PCR amplification from archival tissue offers a novel approach for studying the interactions between potential neuroprotective elements in the host and virulence determinants in HIV that may contribute to differences in susceptibility to ADC.

AIDS Dementia Complex↗
PubMed2006

Interplay of Darwinian and frequency-dependent selection in the host-associated microbial populations.

In order to analyze the microevolutionary processes in host-associated microorganisms, we simulated the dynamics of rhizobia populations composed of a parental strain and its mutants possessing the altered fitness within "plant-soil" system. The population dynamics was presented as a series of cycles (each one involves "soil-->rhizosphere-->nodules-->soil" succession) described using recurrent equations. For representing the selection and mutation pressures, we used a universal approach based on calculating the shifts in the genetic ratios of competing bacterial genotypes within the particular habitats and across several habitats. Analysis of the model demonstrated that a balanced polymorphism may be established in rhizobia population: mutants with an improved fitness do not supplant completely the parental strain while mutants with a decreased fitness may be maintained stably. This polymorphism is caused by a rescue of low-fitted genotypes via negative frequency-dependent selection (FDS) that is implemented during inoculation of nodules and balances the Darwinian selection that occurs during multiplication or extinction of bacteria at different habitats. The most diverse populations are formed if the rhizobia are equally successful in soil and nodules, while a marked preference for any of these habitats results in the decrease of diversity. Our simulation suggests that FDS can maintain the mutualistic rhizobia-legume interactions under the stress conditions deleterious for surviving the bacterial strains capable for intensive N2 fixation. Genetic consequences of releasing the modified rhizobia strains may be addressed using the presented model.

Colony Count, Microbial↗
PubMed1995

Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus.

We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral burden. Her CD4+ T-cell count has fluctuated around a mean of 399 cells per microliters, with little change in lymphocyte subset percentages. Strong cellular immune responses to HIV-1 epitopes by this patient have been demonstrated. We now report the results of an intensive molecular genetic analysis of the HIV-1 proviral quasispecies from this patient sampled over 5 years. Long terminal repeat region sequences supported the argument for normal basal and Tat-mediated promoter activities. Sequential sequencing of the nef gene revealed a low frequency (8.3%) of defective genes and a striking lack of sequence evolution. Functional analysis of predominant nef genes by both a cell surface CD4 downregulation and a viral infectivity complementation assay showed wild-type function. In contrast, sequential analysis of an amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the presence of inactivating mutations in 64% of the clones. These data suggest that this patient, initially infected with a virulent swarm of HIV-1, is presently infected with a more-attenuated viral quasispecies as a result of effective host immunity.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Leishmania histone H1 overexpression delays parasite cell-cycle progression, parasite differentiation and reduces Leishmania infectivity in vivo.

Episomal expression of Leishmania histone H1 sense mRNAs in Leishmania major promastigotes was found previously to result in overexpression of this molecule and to reduce parasite infectivity in vitro. Herein, we evaluated the in vivo infectivity of these transfectants, in BALB/c mice, and showed that it is dramatically reduced. No lesions were observed in this group of mice and this was associated with an extremely low number of parasites both in the footpad and in the draining lymph nodes. Interestingly, the transfectants-reduced infectivity was associated with a delay in their cell-cycle progression and differentiation to axenic amastigotes, assessed in vitro. Therefore, the dramatic reduction in their infectivity may be attributed to the above-mentioned phenotypic modifications. As the metazoan linker histone H1(0) homologue is known to delay cell-cycle progression in mammalian cells we investigated whether its Leishmania counterpart, which possesses homology to its C-terminal region, when expressed in mammalian cells may also affect their cell-cycle progression. It was thus shown that Leishmania histone H1 expressed in COS7 and NIH 3T3 cells, delays cell-cycle progression in these cells too. The latter strengthens the phenotype observed in Leishmania and provides evidence that critical functions of histone H1 molecules are conserved throughout evolution.

Animals↗
PubMed1998

The tryptophanase gene cluster of Haemophilus influenzae type b: evidence for horizontal gene transfer.

Among strains of Haemophilus influenzae, the ability to catabolize tryptophan (as detected by indole production) varies and is correlated with pathogenicity. Tryptophan catabolism is widespread (70 to 75%) among harmless respiratory isolates but is nearly universal (94 to 100%) among strains causing serious disease, including meningitis. As a first step in investigating the relationship between tryptophan catabolism and virulence, we have identified genes in pathogenic H. influenzae which are homologous to the tryptophanase (tna) operon of Escherichia coli. The tna genes are located on a 3.1-kb fragment between nlpD and mutS in the H. influenzae type b (Eagan) genome, are flanked by 43-bp direct repeats of an uptake signal sequence downstream from nlpD, and appear to have been inserted as a mobile unit within this sequence. The organization of this insertion is reminiscent of pathogenicity islands. The tna cluster is found at the same map location in all indole-positive strains of H. influenzae surveyed and is absent from reference type d and e genomes. In contrast to H. influenzae, most other Haemophilus species lack tna genes. Phylogenetic comparisons suggest that the tna cluster was acquired by intergeneric lateral transfer, either by H. influenzae or a recent ancestor, and that E. coli may have acquired its tnaA gene from a related source. Genomes of virulent H. influenzae resemble those of pathogenic enterics in having an island of laterally transferred DNA next to mutS.

Amino Acid Sequence↗
PubMedDate not supplied

[Recurrent bacterial endocarditis on mitral and aortic biological prostheses in young drug addicts. The role of transthoracic cardiac echo-Doppler in the diagnosis and assessment of postendocarditis dysfunction].

Bioprosthetic infective endocarditis is a very serious complication since both medical and surgical treatment is associated with a high mortality. We describe a case of a young drug addict who presented 3 recurrent episodes of bacterial endocarditis of mitral and aortic bioprosthetic valves, caused by different virulent germs. All 3 episodes were resolved by medical therapy, but the residual aortic bioprosthetic dysfunction was important and the patient died before surgical replacement. Which was not considered an emergency since the patient was asymptomatic, did not present heart failure and left ventricular function was preserved. Color-Doppler echocardiography permitted us to visualize the vegetations and to establish and follow the evolution of residual bioprosthetic dysfunction.

Adult↗
PubMed2002

Salmonella effectors within a single pathogenicity island are differentially expressed and translocated by separate type III secretion systems.

Pathogenicity islands (PAIs) are large DNA segments in the genomes of bacterial pathogens that encode virulence factors. Five PAIs have been identified in the Gram-negative bacterium Salmonella enterica. Two of these PAIs, Salmonella pathogenicity island (SPI)-1 and SPI-2, encode type III secretion systems (TTSS), which are essential virulence determinants. These 'molecular syringes' inject effectors directly into the host cell, whereupon they manipulate host cell functions. These effectors are either encoded with their respective TTSS or scattered elsewhere on the Salmonella chromosome. Importantly, SPI-1 and SPI-2 are expressed under distinct environmental conditions: SPI-1 is induced upon initial contact with the host cell, whereas SPI-2 is induced intracellularly. Here, we demonstrate that a single PAI, in this case SPI-5, can encode effectors that are induced by distinct regulatory cues and targeted to different TTSS. SPI-5 encodes the SPI-1 TTSS translocated effector, SigD/SopB. In contrast, we report that the adjacently encoded effector PipB is part of the SPI-2 regulon. PipB is translocated by the SPI-2 TTSS to the Salmonella-containing vacuole and Salmonella-induced filaments. We also show that regions of SPI-5 are not conserved in all Salmonella spp. Although sigD/sopB is present in all Salmonella spp., pipB is not found in Salmonella bongori, which also lacks a functional SPI-2 TTSS. Thus, we demonstrate a functional and regulatory cross-talk between three chromosomal PAIs, SPI-1, SPI-2 and SPI-5, which has significant implications for the evolution and role of PAIs in bacterial pathogenesis.

Animals↗
PubMed1991

Evidence for common ancestry of a chestnut blight hypovirulence-associated double-stranded RNA and a group of positive-strand RNA plant viruses.

Computer-assisted analysis of the putative polypeptide products encoded by the two open reading frames present in a large virus-like double-stranded RNA, L-dsRNA, associated with hypovirulence of the chestnut blight fungus, Cryphonectria parasitica, revealed five distinct domains with significant sequence similarity to previously described conserved domains within plant potyvirus-encoded polyproteins. These included the putative RNA-dependent RNA polymerase, RNA helicase, two papain-like cysteine proteases related to the potyvirus helper-component protease, and a cysteine-rich domain of unknown function similar to the N-terminal portion of the potyvirus helper-component protein. Phylogenetic trees derived from the alignment of the polymerase domains of L-dsRNA, a subset of positive-stranded RNA viruses, and double-stranded RNA viruses, using three independent algorithms, suggested that the hypovirulence-associated dsRNA and potyvirus genomes share a common ancestry. However, comparison of the organization of the conserved domains within the encoded polyproteins of the respective viruses indicated that the proposed subsequent evolution involved extensive genome rearrangement.

Amino Acid Sequence↗
PubMed1999

Five-transmembrane domains appear sufficient for a G protein-coupled receptor: functional five-transmembrane domain chemokine receptors.

The putative seven-transmembrane (TM) domains have been the structural hallmark for the superfamily of heterotrimeric G protein-coupled receptors (GPCRs) that regulate a variety of cellular functions by mediating a large number of extracellular signals. Five-TM GPCR mutants of chemokine receptor CCR5 and CXCR4, the N-terminal segment of which connected directly to TM3 as a result of a deletion of TM1-2 and the first intracellular and extracellular loops, have been obtained in this study. Laser confocal microscopy and flow cytometry analysis revealed that these five-TM mutant GPCRs were expressed stably on the cell surface after transfection into human embryonic kidney 293 cells. The five-TM CCR5 and CXCR4 functioned as normal chemokine receptors in mediating chemokine-stimulated chemotaxis, Ca2+ influx, and activation of pertussis toxin-sensitive G proteins. Like the wild-type GPCRs, the five-TM mutant receptors also underwent agonist-dependent internalization and desensitization and were subjected to regulation by GPCR kinases and arrestins. Our study indicates that five-TM domains, at least in the case of CCR5 and CXCR4, appear to meet the minimum structural requirements for a functional GPCR and suggests possible existence of functional five-TM GPCRs in nature during evolution.

1-Methyl-3-isobutylxanthine↗
PubMed2005

Diverse phenotypes resulting from polyphosphate kinase gene (ppk1) inactivation in different strains of Helicobacter pylori.

Connections among biochemical pathways should help buffer organisms against environmental stress and affect the pace and trajectory of genome evolution. To explore these ideas, we studied consequences of inactivating the gene for polyphosphate kinase 1 (ppk1) in strains of Helicobacter pylori, a genetically diverse gastric pathogen. The PPK1 enzyme catalyzes synthesis of inorganic polyphosphate (poly P), a reservoir of high-energy phosphate bonds with multiple roles. Prior analyses in less-fastidious microbes had implicated poly P in stress resistance, motility, and virulence. In our studies, ppk1 inactivation caused the expected near-complete absence of poly P (>250-fold decrease) but had phenotypic effects that differed markedly among unrelated strains: (i) poor initial growth on standard brain heart infusion agar (five of six strains tested); (ii) weakened colonization of mice (4 of 5 strains); (iii) reduced growth on Ham's F-12 agar, a nutritionally limiting medium (8 of 11 strains); (iv) heightened susceptibility to metronidazole (6 of 17 strains); and (v) decreased motility in soft agar (1 of 13 strains). Complementation tests confirmed that the lack of growth of one Deltappk1 strain on F-12 agar and the inability to colonize mice of another were each due to ppk1 inactivation. Thus, the importance of ppk1 to H. pylori differed among strains and the phenotypes monitored. We suggest that quantitative interactions, as seen here, are common among genes that affect metabolic pathways and that H. pylori's high genetic diversity makes it well suited for studies of such interactions, their underlying mechanisms, and their evolutionary consequences.

Animals↗
PubMed2004

Long-term excretion of vaccine-derived poliovirus by a healthy child.

A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.

Animals↗
PubMed1998

Molecular evolution of dengue type 2 virus in Thailand.

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Dengue↗
PubMed1991

NS 1 gene sequences from eight dengue-2 viruses and their evolutionary relationships with other dengue-2 viruses.

The nucleotide sequences of the NS 1 genes from five Thai and three Sri Lankan dengue-2 viruses were determined by sequencing the viral RNA using synthetic oligonucleotide primers. The results were shown to be similar to four published dengue-2 NS 1 sequences and the classification of these genes was compared with the one obtained for the envelope genes of the same viruses. The classification was similar and showed that the Thai isolates could be divided into two separate groups and that the Sri Lankan isolates were distinct. We found no correlation between disease severity, serological response (1 degree or 2 degrees), or year of isolation and various aspects of NS 1 protein sequence variation; and no particular amino acid changes were correlated with virulence. The sequences were combined with those published and classified elsewhere to provide a comprehensive E/NS 1 gene taxonomy of dengue-2 virus isolates.

Adolescent↗
PubMed2006

Common infection strategies of pathogenic eukaryotes.

Pathogenic eukaryotes belong to several distinct phylogenetic lineages and have evolved the ability to colonize a range of hosts, including animals and plants. Pathogenic lifestyles have evolved repeatedly in eukaryotes, indicating that unique molecular processes are involved in host infection. However, evidence is now emerging that divergent eukaryotic pathogens might share common mechanisms of pathogenicity. The results from recent studies demonstrate that Plasmodium falciparum and Phytophthora infestans use equivalent host-targeting signals to deliver virulence adhesins and avirulence gene products into human and plant cells, respectively. Remodelling of host cells by different eukaryotic pathogens might therefore share some common features.

Amino Acid Motifs↗
PubMed2007

An H-NS-like stealth protein aids horizontal DNA transmission in bacteria.

The Sfh protein is encoded by self-transmissible plasmids involved in human typhoid and is closely related to the global regulator H-NS. We have found that Sfh provides a stealth function that allows the plasmids to be transmitted to new bacterial hosts with minimal effects on their fitness. Introducing the plasmid without the sfh gene imposes a mild H-NS(-) phenotype and a severe loss of fitness due to titration of the cellular pool of H-NS by the A+T-rich plasmid. This stealth strategy seems to be used widely to aid horizontal DNA transmission and has important implications for bacterial evolution.

Bacterial Proteins↗
PubMed1998

Type III protein secretion systems in bacterial pathogens of animals and plants.

Various gram-negative animal and plant pathogens use a novel, sec-independent protein secretion system as a basic virulence mechanism. It is becoming increasingly clear that these so-called type III secretion systems inject (translocate) proteins into the cytosol of eukaryotic cells, where the translocated proteins facilitate bacterial pathogenesis by specifically interfering with host cell signal transduction and other cellular processes. Accordingly, some type III secretion systems are activated by bacterial contact with host cell surfaces. Individual type III secretion systems direct the secretion and translocation of a variety of unrelated proteins, which account for species-specific pathogenesis phenotypes. In contrast to the secreted virulence factors, most of the 15 to 20 membrane-associated proteins which constitute the type III secretion apparatus are conserved among different pathogens. Most of the inner membrane components of the type III secretion apparatus show additional homologies to flagellar biosynthetic proteins, while a conserved outer membrane factor is similar to secretins from type II and other secretion pathways. Structurally conserved chaperones which specifically bind to individual secreted proteins play an important role in type III protein secretion, apparently by preventing premature interactions of the secreted factors with other proteins. The genes encoding type III secretion systems are clustered, and various pieces of evidence suggest that these systems have been acquired by horizontal genetic transfer during evolution. Expression of type III secretion systems is coordinately regulated in response to host environmental stimuli by networks of transcription factors. This review comprises a comparison of the structure, function, regulation, and impact on host cells of the type III secretion systems in the animal pathogens Yersinia spp., Pseudomonas aeruginosa, Shigella flexneri, Salmonella typhimurium, enteropathogenic Escherichia coli, and Chlamydia spp. and the plant pathogens Pseudomonas syringae, Erwinia spp., Ralstonia solanacearum, Xanthomonas campestris, and Rhizobium spp.

Animals↗