Movement can mediate temporal mismatches between resource availability and biological events in host–pathogen interactions

Global change is shifting the timing of biological events, leading to temporal mismatches between biological events and resource availability. These temporal mismatches can threaten species’ populations. Importantly, temporal mismatches not only exert strong pressures on the population dynamics of the focal species, but can also lead to substantial changes in pairwise species interactions such as host–pathogen systems. We adapted an established individual‐based model of host–pathogen dynamics. The model describes a viral agent in a social host, while accounting for the host''s explicit movement decisions. We aimed to investigate how temporal mismatches between seasonal resource availability and host life‐history events affect host–pathogen coexistence, that is, disease persistence. Seasonal resource fluctuations only increased coexistence probability when in synchrony with the hosts’ biological events. However, a temporal mismatch reduced host–pathogen coexistence, but only marginally. In tandem with an increasing temporal mismatch, our model showed a shift in the spatial distribution of infected hosts. It shifted from an even distribution under synchronous conditions toward the formation of disease hotspots, when host life history and resource availability mismatched completely. The spatial restriction of infected hosts to small hotspots in the landscape initially suggested a lower coexistence probability due to the critical loss of susceptible host individuals within those hotspots. However, the surrounding landscape facilitated demographic rescue through habitat‐dependent movement. Our work demonstrates that the negative effects of temporal mismatches between host resource availability and host life history on host–pathogen coexistence can be reduced through the formation of temporary disease hotspots and host movement decisions, with implications for disease management under disturbances and global change.     

A call to order at the spirochaetal host–pathogen interface

As the Lyme disease spirochaete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype‐defining surface lipoproteins. These peripherally membrane‐anchored virulence factors mediate niche‐specific interactions with vector/host factors and protect the spirochaete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo ‘use it or lose it’ gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host.     

Role of serine protease inhibitors in insect‐host‐pathogen interactions

Serine protease inhibitors (serpins), evolutionary old, structurally conserved molecules, are a superfamily of proteins found in almost all living organisms. Serpins are relatively large, typically 350–500 amino acids in length, with three β‐sheets and seven to nine α‐helices folding into a conserved tertiary structure with a reactive center loop. Serpins perform various physiological functions in insects, including development, digestion, host‐pathogen interactions, and innate immune response. In insects, the innate immune system is characterized as the first and major defense system against the invasion of microorganisms. Serine protease cascades play a critical role in the initiation of innate immune responses, such as melanization and the production of antimicrobial peptides, and are strictly and precisely regulated by serpins. Herein, we provide a microreview on the role of serpins in the insect‐host‐pathogen interactions, emphasizing their role in immune responses, particularly in diamondback moth (Plutella xylostella), highlighting the important discoveries and also the gaps that remain to be explored in future studies.     

Multiple deletions in the polyketide synthase gene repertoire of Mycobacterium tuberculosis reveal functional overlap of cell envelope lipids in host–pathogen interactions

Several specific lipids of the cell envelope are implicated in the pathogenesis of M. tuberculosis (Mtb), including phthiocerol dimycocerosates (DIM) that have clearly been identified as virulence factors. Others, such as trehalose‐derived lipids, sulfolipids (SL), diacyltrehaloses (DAT) and polyacyltrehaloses (PAT), are believed to be essential for Mtb virulence, but the details of their role remain unclear. We therefore investigated the respective contribution of DIM, DAT/PAT and SL to tuberculosis by studying a collection of mutants, each with impaired production of one or several lipids. We confirmed that among those with a single lipid deficiency, only strains lacking DIM were affected in their replication in lungs and spleen of mice in comparison to the WT Mtb strain. We found also that the additional loss of DAT/PAT, and to a lesser extent of SL, increased the attenuated phenotype of the DIM‐less mutant. Importantly, the loss of DAT/PAT and SL in a DIM‐less background also affected Mtb growth in human monocyte‐derived macrophages (hMDMs). Fluorescence microscopy revealed that mutants lacking DIM or DAT/PAT were localized in an acid compartment and that bafilomycin A1, an inhibitor of phagosome acidification, rescued the growth defect of these mutants. These findings provide evidence for DIM being dominant virulence factors that mask the functions of lipids of other families, notably DAT/PAT and to a lesser extent of SL, which we showed for the first time to contribute to Mtb virulence.     

A peptide resource for the analysis of Staphylococcus aureus in host–pathogen interaction studies

Staphylococcus aureus is an opportunistic human pathogen, which can cause life‐threatening disease. Proteome analyses of the bacterium can provide new insights into its pathophysiology and important facets of metabolic adaptation and, thus, aid the recognition of targets for intervention. However, the value of such proteome studies increases with their comprehensiveness. We present an MS–driven, proteome‐wide characterization of the strain S. aureus HG001. Combining 144 high precision proteomic data sets, we identified 19 109 peptides from 2088 distinct S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides were further characterized concerning pI, GRAVY, and detectability scores in order to understand the low peptide coverage of 8.7% (19 109 out of 220 245 theoretical peptides). The high quality peptide‐centric spectra have been organized into a comprehensive peptide fragmentation library (SpectraST) and used for identification of S. aureus‐typic peptides in highly complex host–pathogen interaction experiments, which significantly improved the number of identified S. aureus proteins compared to a MASCOT search. This effort now allows the elucidation of crucial pathophysiological questions in S. aureus‐specific host–pathogen interaction studies through comprehensive proteome analysis. The S. aureus‐specific spectra resource developed here also represents an important spectral repository for SRM or for data‐independent acquisition MS approaches. All MS data have been deposited in the ProteomeXchange with identifier PXD000702 ( http://proteomecentral.proteomexchange.org/dataset/PXD000702 ).     

The mammalian complement system as an epitome of host–pathogen genetic conflicts

The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial‐encoded complement‐interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins. Positively selected sites in CFH and C4BPA account for the human specificity of gonococcal infection. Bacterial interactors, evolved adaptively as well, with selected sites located at interaction surfaces with primate complement proteins. These results epitomize the expectation under a genetic conflict scenario whereby the host's and the pathogen's genes evolve within binding avoidance‐binding seeking dynamics. In silico mutagenesis and protein–protein docking analyses supported this by showing that positively selected sites, both in the host's and in the pathogen's interacting partner, modulate binding.     

The evolution of sexual dimorphism and its potential impact on host–pathogen coevolution

Sex and infection are intimately linked. Many diseases are spread by sexual contact, males are thought to evolve exaggerated sexual signals to demonstrate their immune robustness, and pathogens have been shown to direct the evolution of recombination. In all of these examples, infection is influencing the evolution of male and female fitness, but less is known about how sex differences influence pathogen fitness. A defining characteristic of sexual dimorphism is not only divergent phenotypes, but also a complex genetic architecture involving changes in genetic correlations among shared fitness traits, and differences in the accumulation of mutations—all of which may affect selection on an invading pathogen. Here, we outline the implications that the genetics of sexual dimorphism can have for host–pathogen coevolution and argue that male–female differences influence more than just the environment that a pathogen experiences.     

Intracellular imaging of host‐pathogen interactions using combined CARS and two‐photon fluorescence microscopies

Intracellular imaging is a key tool in the investigation of host‐pathogen interactions. Advances in this area are particularly sought to understand the effect of viral infection processes on the host cell and its metabolic functions including those cases where host cell lipid metabolism is modulated as a result of infection. We demonstrate the use of combined coherent anti‐Stokes Raman scattering (CARS) and two‐photon fluorescence microscopies to image fibroblast cells infected by cytomegalovirus. CARS is used to image the host cell membrane, lipid droplets and morphology of the nucleus. Cell nuclei are found to expand during infection, approximately doubling in area. Some cells also show accumulations of lipid droplets at the nuclear periphery. Using a genetically modified virus strain expressing the green fluorescent protein also enables two‐photon imaging of the same cells to reveal the location, nature and extent of viral protein expression. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Snapshots of native pre-50S ribosomes reveal a biogenesis factor network and evolutionary specialization

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Developmental timing of extreme temperature events (heat waves) disrupts host–parasitoid interactions

1. When thermal tolerances differ between interacting species, extreme temperature events (heat waves) will alter the ecological outcomes. The parasitoid wasp Cotesia congregata suffers high mortality when reared throughout development at temperatures that are nonstressful for its host, Manduca sexta. However, the effects of short‐term heat stress during parasitoid development are unknown in this host–parasitoid system.
2. Here, we investigate how duration of exposure, daily maximum temperature, and the developmental timing of heat waves impact the performance of C. congregata and its host¸ M. sexta. We find that the developmental timing of short‐term heat waves strongly determines parasitoid and host outcomes.
3. Heat waves during parasitoid embryonic development resulted in complete wasp mortality and the production of giant, long‐lived hosts. Heat waves during the 1st‐instar had little effect on wasp success, whereas heat waves during the parasitoid''s nutritionally and hormonally critical 2nd instar greatly reduced wasp emergence and eclosion. The temperature and duration of heat waves experienced early in development determined what proportion of hosts had complete parasitoid mortality and abnormal phenotypes.
4. Our results suggest that the timing of extreme temperature events will be crucial to determining the ecological impacts on this host–parasitoid system. Discrepancies in thermal tolerance between interacting species and across development will have important ramifications on ecosystem responses to climate change.

     

Signatures of selection and host‐adapted gene expression of the Phytophthora infestans RNA silencing suppressor PSR2

Phytophthora infestans is a devastating pathogen in agricultural systems. Recently, an RNA silencing suppressor (PSR2, ‘Phytophthora suppressor of RNA silencing 2’) has been described in P. infestans. PSR2 has been shown to increase the virulence of Phytophthora pathogens on their hosts. This gene is one of the few effectors present in many economically important Phytophthora species. In this study, we investigated: (i) the evolutionary history of PSR2 within and between species of Phytophthora; and (ii) the interaction between sequence variation, gene expression and virulence. In P. infestans, the highest PiPSR2 expression was correlated with decreased symptom expression. The highest gene expression was observed in the biotrophic phase of the pathogen, suggesting that PSR2 is important during early infection. Protein sequence conservation was negatively correlated with host range, suggesting host range as a driver of PSR2 evolution. Within species, we detected elevated amino acid variation, as observed for other effectors; however, the frequency spectrum of the mutations was inconsistent with strong balancing selection. This evolutionary pattern may be related to the conservation of the host target(s) of PSR2 and the absence of known corresponding R genes. In summary, our study indicates that PSR2 is a conserved effector that acts as a master switch to modify plant gene regulation early during infection for the pathogen's benefit. The conservation of PSR2 and its important role in virulence make it a promising target for pathogen management.     

Louse-borne relapsing fever—A systematic review and analysis of the literature: Part 2—Mortality,Jarisch–Herxheimer reaction,impact on pregnancy

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch–Herxheimer reaction (JHR), and impact on pregnancy.Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases.The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown.Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases.LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.