The macroecology of infectious diseases: a new perspective on global‐scale drivers of pathogen distributions and impacts

Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence.     

A genetically distinct hybrid zone occurs for two globally invasive mosquito fish species with striking phenotypic resemblance

Hybrid zones allow for the investigation of incipient speciation and related evolutionary processes of selection, gene flow, and migration. Interspecific dynamics, like competition, can impact the size, shape, and directional movement of species in hybrid zones. Hybrid zones contribute to a paradox for the biological species concept because interbreeding between species occurs while parental forms remain distinct. A long‐standing zone of intergradation or introgression exists for eastern and western mosquito fish (Gambusia holbrooki and G. affinis) around Mobile Bay, AL. The region has been studied episodically, over decades, making it perfect for addressing temporal dynamics and for providing a deeper understanding of the genetics of these periodically reclassified fishes (as species or subspecies). We used six microsatellite markers to assess the current population structure and gene flow patterns across 19 populations of mosquito fish and then compared our results with historical data. Genetic evidence demonstrates that the current hybrid zone is located in a similar geographic region as the historical one, even after three decades. Hybrid fish, however, demonstrate relatively low heterozygosity and are genetically distinct from western and eastern mosquito fish populations. Fin ray counts, sometimes used to distinguish the two species from one another, demonstrate more eastern (G. holbrooki) phenotype fish within the molecular genetic hybrid zone today. Mosquito fish are globally invasive, often found on the leading edge of flooded waters that they colonize, so the impact of hurricanes in the wake of climate change was also evaluated. An increase in the frequency and intensity of hurricanes in the hybrid region has occurred, and this point warrants further attention since hurricanes are known to move these aggressive, invasive species into novel territory. This work contributes to our classical understanding of hybrid zone temporal dynamics, refines our understanding of mosquito fish genetics in their native range, evaluates important genotype–phenotype relationships, and identifies a potential new impact of climate change.     

Vegetation response to removal of non-native feral pigs from Hawaiian tropical montane wet forest

Globally, non-native ungulates threaten native biodiversity, alter biotic and abiotic factors regulating ecological processes, and incur significant economic costs via herbivory, rooting, and trampling. Removal of non-native ungulates is an increasingly common and crucial first step in conserving and restoring native forests. However, removal is often controversial and there is currently little information on plant community responses to this management action. Here, we examine the response of native and non-native understory vegetation in paired sites inside and outside of exclosures across a 6.5–18.5 year chronosequence of feral pig (Sus scrofa) removal from canopy-intact Hawaiian tropical montane wet forest. Stem density and cover of native plants, species richness of ground-rooted native woody plants, and abundance of native plants of conservation interest were all significantly higher where feral pigs had been removed. Similarly, the area of exposed soil was substantially lower and cover of litter and bryophytes was greater with feral pig removal. Spatial patterns of recruitment were also strongly affected. Whereas epiphytic establishment was similar between treatments, the density of ground-rooted woody plants was four times higher with feral pig removal. Abundance of invasive non-native plants also increased at sites where they had established prior to feral pig removal. We found no patterns in any of the measured variables with time, suggesting that commonly occurring species recover within 6.5 years of feral pig removal. Recovery of species of conservation interest, however, was highly site specific and limited to areas that possessed remnant populations at the time of removal, indicating that some species take much longer (>18.5 years) to recover. Feral pig removal is the first and most crucial step for conservation of native forests in this area, but subsequent management should also include control of non-native invasive plants and outplanting native species of conservation interest that fail to recruit naturally.     

Metabolomic Derangements Are Associated with Mortality in Critically Ill Adult Patients

Objective

To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults.

Rationale

Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.

Methods

We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study.

Results

We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations).

Conclusion

Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.     

Feeny revisited: condensed tannins as anti-herbivore defences in leaf-chewing herbivore communities of Quercus

Abstract. 1. Community level oak–tannin–insect patterns have been largely unexplored since Paul Feeny's ground‐breaking research. Two hypotheses were tested for Quercus velutina and Q. alba in the Missouri Ozarks: abundance and richness of leaf‐chewing herbivores are negatively correlated with foliar condensed tannin concentrations and variation in condensed tannin concentrations explains variation in herbivore community structure. 2. In 2001, foliar condensed tannins in the understorey and canopy of these two oak species were quantified simultaneously with censuses of herbivores in May, during leaf expansion, and in June and August, when leaves were fully expanded. Thirty‐eight of the 134 species encountered had densities sufficient to be analysed individually (n = 10). Of those, Acronicta increta (Noctuidae) and Attelabus sp. (Curculionidae), both oak specialists, were negatively correlated with condensed tannins in the canopy of Q. alba. One additional specialist, Chionodes pereyra (Gelechiidae), was marginally negatively correlated with condensed tannins in the understorey of Q. velutina. Understorey species richness of May Q. velutina herbivores was negatively correlated with condensed tannins, as were total canopy insect density and species richness of August herbivores on Q. alba. 3. Principal component analysis (PCA) of insect abundances indicated that understorey and canopy Q. velutina and Q. alba had different communities of leaf‐chewing insects. Furthermore, condensed tannin levels contributed significantly to variation in PCA scores for Q. velutina, explaining 25% of the total variation. 4. Overall, these results indicate that specialists were more likely than generalists both to correlate negatively with condensed tannins and to occur in lower tannin habitats; abundance and richness of both early and late season fauna correlated negatively with tannins; and species were more likely to correlate negatively with condensed tannins when feeding on Q. alba than on Q. velutina and when feeding in the canopy than in the understorey. Future studies of tannin–insect interactions should manipulate leaf quality in combination with manipulations of other factors that likely influence community structure.     

An Escherichia coli MutY mutant without the six-helix barrel domain is a dimer in solution and assembles cooperatively into multisubunit complexes with DNA

Escherichia coli MutY is an adenine and weak guanine DNA glycosylase involved in reducing the mutagenic effects of 7,8-dihydro-8-oxoguanine (GO). MutY contains three structural domains: an iron-sulfur module, a six-helix barrel module with the helix-hairpin-helix motif, and a C-terminal domain. Here, we demonstrate that the mutant MutY(Delta26-134), which lacks the six-helix barrel domain, cannot complement the mutator phenotype of a mutY mutant in vivo. However, the mutant can still bind DNA and has weak catalytic activity at high enzyme concentrations. The mutant is a dimer in solution and assembled into two and multiple (up to five) complexes with 20- and 44-bp DNA fragments, respectively, in a concentration-dependent manner. Higher order complexes with DNA substrates containing A/GO mismatches were formed at lower protein concentrations than with the A/G mismatch and homoduplex DNA. Measurement of equilibrium binding using fluorescence anisotropy showed that the mutant protein retains some specificity for A/GO-containing DNA substrates and that the binding event is highly cooperative. This is consistent with the MutY structure determined, which indicates that GO specificity is contributed by both the six-helix barrel and C-terminal domains. The nonspecific binding of MutY(Delta26-134) to DNA suggests a model in which the specific binding of mismatched DNA by MutY involves sequential interactions, in which one MutY molecule scans the DNA and enhances binding of another MutY molecule to the A/GO mismatch.     

New gammaproteobacteria associated with blood-feeding leeches and a broad phylogenetic analysis of leech endosymbionts

Many monophagous animals have coevolutionary relationships with bacteria that provide unavailable nutrients to the host. Frequently, these microbial partners are vertically inherited and reside in specialized structures or tissues. Here we report three new lineages of bacterial symbionts of blood-feeding leeches, one from the giant Amazonian leech, Haementeria ghilianii, and two others from Placobdelloides species. These hosts each possess a different mycetome or esophageal organ morphology where the bacterial cells are located. DNA sequencing of the bacterial 16S rRNA genes and fluorescent in situ hybridization placed these symbionts in two separate clades in the class Gammaproteobacteria. We also conducted a broad phylogenetic analysis of the herein-reported DNA sequences as well as others from bacterial symbionts reported elsewhere in the literature, including alphaproteobacterial symbionts from the leech genus Placobdella as well as Aeromonas veronii from the medicinal leech, Hirudo medicinalis, and a Rickettsia sp. detected in Hemiclepsis marginata. Combined, these results indicate that blood-feeding leeches have forged bacterial partnerships at least five times during their evolutionary history.