Facultative parasites and host respiration II. Diseased tissue from which the pathogen has been removed

Summary Aseptic tissue cultures of Crown-gall ofScorzonera hispanica L. andHelianthus tuberosus L. have a higher rate of respiration than tissue cultures of the respective healthy tissue. Cultures of healthy tissue ofS. hispanica which have been subjected to high concentrations of auxin (napthalene acetic acid) until they reached an habituated stage in which they could grow without addition of the auxin, show an increased respiration similar to that of Crown-gall tissue cultures. It is concluded that the respiratory increase shown by Crown-gall tissue is not due to the retentive effect of a respiratory toxin alone but due also to a pathogen induced auxin metabolism.This work formed part of a Ph. D. thesis submitted to the Univ. of London, July 1961.     

Facultative parasites and host respiration. I. Healthy tissue adjacent to the site of infection

Summary The respiration, as measured by oxygen uptake, was higher for healthy tissue adjacent to soft rots of apple (var. Bramley) caused byPenicillium expansum Link andThom. andBotrytis cinerea Fr. and of potato tuber (var. Arran Banner) caused byErwinia aroideae Townsend, than tissue at a more distant site. The respiration of tissue adjacent to a physiological rot caused by bruising was not affected. It was concluded that there is diffusion of a substance(s) from the site of infection which causes an increase in the rate of respiration of the adjacent tissue.This work formed part of a Ph. D. thesis submitted to the University of London, July 1961.     

Population dynamics of killing parasites which reproduce in the host

For a parasitic infection in human hosts a model is derived from basic assumptions on the population structure of the host, in particular mortality depending on age and parasite load, and on the reproduction and transmission of parasites. The model assumes the form of a system of partial differential equations. The paper contains proofs of local and global existence and existence and uniqueness of nontrivial stationary states, and a discussion of the relation to birth and death processes and other models for parasitic infections.     

Interactions between Leishmania parasites and host cells.

Several species of protozoa belonging to the genus Leishmania are pathogenic for humans, causing visceral and cutaneous diseases. They are transmitted by phlebotomine sandflies as flagellated promastigotes to mammals hosts, where they live as aflagellated amastigotes mainly within macrophages. Studies performed on mice infected with Leishmania major demonstrated that host defence against this infection depends on the interleukin-12-driven expansion of the T helper 1 cell subset, with production of cytokines such as interferon-gamma, which activate macrophages for parasite killing through the release of nitric oxide. The parasitocidal role of this radical is now emerging also in the human and canine model. Healing or progression of the infection is related to the genetic and immune status of the host, and to the virulence of different species and strains of Leishmania. The parasite survival ultimately depends on the ability to evade the host immune response by several mechanisms. Among them, inhibition of the signal transduction pathway of the host cells is particularly important. In fact, promastigotes inhibit protein kinase C activation, cause Ca++ influx into the host cell and decrease the levels of myristoylated alanine-rich C kinase substrate-related proteins, which are substrates for PKC. In addition, Leishmania infection blocks IFN-gamma-induced tyrosine kinase phosphorylation, with consequent impairment of signalling for IL-12 and nitric oxide production. Finally, Leishmania activates protein phosphotyrosine phosphatases, which down-regulate mitogen-activated protein kinase signalling and c-fos and nitric oxide synthase expression. New pharmacological applications, including protein tyrosine phosphatase and protein farnesyltransferase inhibitors, are being evaluated against leishmaniosis in vitro and in vivo in the murine model.     

Migration through host cells by apicomplexan parasites.

In what appears to be an essential prelude to establish a successful infection in the mammalian host, Plasmodium sporozoites move rapidly through several host cells breaching the cell plasma membranes in the process. This mode of invasion precedes the 'traditional' mode in which the sporozoite enters by invagination of the host cell membrane and develops within a parasitophorous vacuole. Here we revisit the existing literature that supports the presence of similar invasive behaviors in other apicomplexan parasites.     

African trypanosomes contain calmodulin which is distinct from host calmodulin

Studies were initiated to determine whether African trypanosomes utilize Ca2+ fluxes to coordinate complex morphological and biochemical life cycle changes. We have identified the ubiquitous intracellular Ca2+ receptor, calmodulin, in two developmental stages of Trypanosoma brucei rhodesiense. The transition from rapidly dividing, slender bloodstream trypomastigotes to slow growing procyclics in axenic culture was accompanied by changes in specific calmodulin content (3 micrograms/mg cell protein to 1 microgram/mg cell protein, respectively) and a shift in intracellular calmodulin distribution, Trypanosome calmodulin is physically and functionally distinct from that of host tissues, including bovine brain and rat erythrocytes. It is similar to but distinct from Tetrahymena calmodulin. Comparisons among these proteins isolated from the four sources were made using the following criteria: (1) mobility on sodium dodecyl sulfate discontinuous polyacrylamide gels; (2) Ca2+-induced conformational changes; (3) CNBr-cleavage fragments; (4) activation of bovine brain cyclic nucleotide phosphodiesterase in both a Ca2+-dependent and calmodulin-dependent manner; (5) activation of human erythrocyte (Ca2+ + Mg2+)-ATPase; and (6) inhibition of calmodulin activity by trifluoperazine and penfluridol. Trifluoperazine but not trifluoperazine sulfoxide was cytotoxic to trypanosomes in vitro. Half maximal effect occurred at 15 microM. We conclude that calmodulin is a functional component of Africal trypanosomes and suggest that it plays an important role in mediating the host-parasite relationship.     

Physiological studies onMarphysa gravelyi VII. Tissue respiration

Summary 1. The respiratory rate of body tissues of the polychaeteM. gravelyi ranged from 3.13 µl/mg/hr to 6.34 µl/mg/hr in the four experimental salinities 10 , 14, 17 and 24 Since similar estimations in other polychaetes are not available in literature a comparison is difficult. However, the trends, i. e., increase of respiratory rates with increasing salinity, are similar to those reported for whole individuals ofN. diversicolor.2. InM. gravelyi, both the organic and inorganic ions are regulated. It is argued that the trend reported above may be traced to the operation of an effective ion transport system.3. Two adaptations that may help to understand the trend of evolution inM. gravelyi are the reduction in permeability and the lowering of the body fluid concentration.4. These two adaptations may indicate a tendency towards life in freshwater. A few other features, such as corresponding changes in the reproductive patterns ofM. gravelyi and the geographical distribution of the genusMarphysa support this assumption.

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Physiologische Untersuchungen anMarphysa gravelyi. VII. Gewebsatmung

Kurzfassung Die respiratorische Aktivität des Körpergewebes vonMarphysa gravelyi Southern, einem brackwasserlebenden Polychaeten, wurde in verschiedenen Salinitätsstufen (10, 14, 17 und 24 S) gemessen. Es wurde festgestellt, daß mit zunehmendem Salzgehalt des Mediums der Sauerstoffverbrauch steigt. Diese Zunahme der Atmungsgröße wird in Beziehung zu einer verstärkten Ionenregulation gesetzt. Auf Grund osmoregulatorischer Befunde wird angenommen, daß bei dieser Art Tendenzen zur Anpassung an eine Existenz im Süßwasser bestehen.

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Dedicated to Professor Dr.Friedrich Krüger on his 65^th birthday, August 18, 1967.     

The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length

Meiotic recombination ensures proper chromosome segregation to form viable gametes and results in gene conversions events between homologs. Conversion tracts are shorter in meiosis than in mitotically dividing cells. This results at least in part from the binding of a complex, containing the Mer3 helicase and the MutLβ heterodimer, to meiotic recombination intermediates. The molecular actors inhibited by this complex are elusive. The Pif1 DNA helicase is known to stimulate DNA polymerase delta (Pol δ) -mediated DNA synthesis from D-loops, allowing long synthesis required for break-induced replication. We show that Pif1 is also recruited genome wide to meiotic DNA double-strand break (DSB) sites. We further show that Pif1, through its interaction with PCNA, is required for the long gene conversions observed in the absence of MutLβ recruitment to recombination sites. In vivo, Mer3 interacts with the PCNA clamp loader RFC, and in vitro, Mer3-MutLβ ensemble inhibits Pif1-stimulated D-loop extension by Pol δ and RFC-PCNA. Mechanistically, our results suggest that Mer3-MutLβ may compete with Pif1 for binding to RFC-PCNA. Taken together, our data show that Pif1’s activity that promotes meiotic DNA repair synthesis is restrained by the Mer3-MutLβ ensemble which in turn prevents long gene conversion tracts and possibly associated mutagenesis.     

An unlikely partnership: parasites, concomitant immunity and host defence.

Concomitant immunity (CI) against macroparasites describes a state of effective anti-larval immunity coupled with persistent adult infection. Experimental studies indicate that immunologically concealed adult worms might promote anti-larval immunity via the release of cross-reactive antigens, thus creating a barrier against continual infection and restricting burden size within the host. CI offers an important potential benefit to established worms by preventing overcrowding within the host. Thus, CI may be interpreted as akin to vaccination; relatively long-lived adult worms 'vaccinate' their host with larval surface antigens and so benefit from reduced conspecific competition. The shared responsibility for host vaccination among adult worms leads to a problem of collective action. Here, we build on earlier analytical findings about the evolutionary forces that shape cooperation among parasites in order to produce a stochastic simulation model of macroparasite social evolution. First, we theoretically investigate a parasite adaptation hypothesis of CI and demonstrate its plausibility under defined conditions, despite the possibility of evolutionary 'cheats'. Then we derive a set of predictions for testing the hypothesis that CI is partly a host-manipulative parasite adaptation. Evidence in support of this model would present an unusual case of adaptive population regulation.     

Diversification and host switching in avian malaria parasites

The switching of parasitic organisms to novel hosts, in which they may cause the emergence of new diseases, is of great concern to human health and the management of wild and domesticated populations of animals. We used a phylogenetic approach to develop a better statistical assessment of host switching in a large sample of vector-borne malaria parasites of birds (Plasmodium and Haemoproteus) over their history of parasite-host relations. Even with sparse sampling, the number of parasite lineages was almost equal to the number of avian hosts. We found that strongly supported sister lineages of parasites, averaging 1.2% sequence divergence, exhibited highly significant host and geographical fidelity. Event-based matching of host and parasite phylogenetic trees revealed significant cospeciation. However, the accumulated effects of host switching and long distance dispersal cause these signals to disappear before 4% sequence divergence is achieved. Mitochondrial DNA nucleotide substitution appears to occur about three times faster in hosts than in parasites, contrary to findings on other parasite-host systems. Using this mutual calibration, the phylogenies of the parasites and their hosts appear to be similar in age, suggesting that avian malaria parasites diversified along with their modern avian hosts. Although host switching has been a prominent feature over the evolutionary history of avian malaria parasites, it is infrequent and unpredictable on time scales germane to public health and wildlife management.     

Replication of minichromosomes in a host in which chromosome replication is random

Minichromosomes are plasmids with the origin of chromosome replication, oriC, as their only origin of replication. In Escherichia coli, minichromosomes are compatible with the chromosome and replicate in a cell-cycle-specific manner at the same time as oriC located on the chromosome initiates replication. In int strains, oriC has been inactivated and replaced by a plasmid origin. Because plasmids control their own replication, chromosome replication is uncoupled from the normal cell-cycle control and is random with respect to the cell cycle in the int strains. We have used an intP1 strain to address the question of whether minicromosome replication is coupled to the replication of the chromosome or is governed by cell-cycle-specific signals. Minichromosome replication was analysed by density-shift experiments and found not to be random in the randomly replicating intP1 host. This suggests that the cell-cycle-specific control functions of oriC replication are operating also in the intP1 strain.     

Infochemicals in mosquito host selection: human skin microflora and Plasmodium parasites.

The interaction between the African malaria vector Anopheles gambiae and its human host has traditionally been viewed within a bitrophic context, considering only the human and the mosquito. Recently, the influence of the Plasmodium parasite on the interaction has been recognized, because it affects the physiology and/or behaviour of humans and mosquitoes. However, studies on odour-mediated host-seeking behaviour of An. gambiae and other Diptera have provided evidence that a fourth group of organisms should be taken into consideration. Human skin microflora play a role in the production of odorous compounds that might function as kairomones for mosquitoes. Here, Marieta Braks, Rob Anderson and Bart Knols introduce the role of human microflora into the process of odour-mediated host selection and review the interaction in a multipartite context so as to identify research avenues that will enhance our limited knowledge of this aspect of malaria transmission.     

Inter- and intraspecific conflicts between parasites over host manipulation

Host manipulation is a common strategy by which parasites alter the behaviour of their host to enhance their own fitness. In nature, hosts are usually infected by multiple parasites. This can result in a conflict over host manipulation. Studies of such a conflict in experimentally infected hosts are rare. The cestode Schistocephalus solidus (S) and the nematode Camallanus lacustris (C) use copepods as their first intermediate host. They need to grow for some time inside this host before they are infective and ready to be trophically transmitted to their subsequent fish host. Accordingly, not yet infective parasites manipulate to suppress predation. Infective ones manipulate to enhance predation. We experimentally infected laboratory-bred copepods in a manner that resulted in copepods harbouring (i) an infective C plus a not yet infective C or S, or (ii) an infective S plus a not yet infective C. An infective C completely sabotaged host manipulation by any not yet infective parasite. An infective S partially reduced host manipulation by a not yet infective C. We hence show experimentally that a parasite can reduce or even sabotage host manipulation exerted by a parasite from a different species.