Lisa S. Goessling

Invasive honeysuckle eradication reduces tick-borne disease risk by altering host dynamics

Despite the ubiquity of invasive organisms and their often deleterious effects on native flora and fauna, the consequences of biological invasions for human health and the ecological mechanisms through which they occur are rarely considered. Here we demonstrate that a widespread invasive shrub in North America, Amur honeysuckle (Lonicera maackii), increases human risk of exposure to ehrlichiosis, an emerging infectious disease caused by bacterial pathogens transmitted by the lone star tick (Amblyomma americanum). Using large-scale observational surveys in natural areas across the St. Louis, Missouri region, we found that white-tailed deer (Odocoileus virginianus), a preeminent tick host and pathogen reservoir, more frequently used areas invaded by honeysuckle. This habitat preference translated into considerably greater numbers of ticks infected with pathogens in honeysuckle-invaded areas relative to adjacent honeysuckle-uninvaded areas. We confirmed this biotic mechanism using an experimental removal of honeysuckle, which caused a decrease in deer activity and infected tick numbers, as well as a proportional shift in the blood meals of ticks away from deer. We conclude that disease risk is likely to be reduced when honeysuckle is eradicated, and suggest that management of biological invasions may help ameliorate the burden of vector-borne diseases on human health.

Blood meal analysis to identify reservoir hosts for Amblyomma americanum ticks

Blood meal analysis identified white-tailed deer as hosts for ticks that carry zoonotic pathogens.

Involvement of Heme in the Degradation of Iron-regulatory Protein 2

Iron-regulatory proteins (IRPs) recognize and bind to specific RNA structures called iron-responsive elements. Mediation of these binding interactions by iron and iron-containing compounds regulates several post-transcriptional events relevant to iron metabolism. There are two known IRPs, IRP1 and IRP2, both of which can respond to iron fluxes in the cell. There is ample evidence that IRP1 is converted by iron to cytoplasmic aconitase in vivo. It has also been shown that, under certain conditions, a significant fraction of IRP1 is degraded in cells exposed to iron or heme. Studies have shown that the degradation of IRP1 that is induced by iron can be inhibited by either desferrioxamine mesylate (an iron chelator) or succinyl acetone (an inhibitor of heme synthesis), whereas the degradation induced by heme cannot. This suggests that heme rather than iron is responsible for this degradation. Several laboratories have shown that IRP2 is also degraded in cells treated with iron salts. We now show evidence suggesting that this IRP2 degradation may be mediated by heme. Thus, in experiments analogous to those used previously to study IRP1, we find that IRP2 is degraded in rabbit fibroblast cells exposed to heme or iron salts. However, as shown earlier with IRP1, both desferrioxamine mesylate and succinyl acetone will inhibit the degradation of IRP2 induced by iron but not that induced by heme.

Effects of the Ferritin Open Reading Frame on Translational Induction by Iron.

Publisher Summary Ferritin—a multimeric iron-storage protein—is evolutionarily conserved from prokaryotes to eukaryotes. It has been proposed that ferritin acts both to store iron for later use and to defend the cytosol against the generation of potentially toxic free radicals via Fenton oxygen chemistry. The regulation of ferritin synthesis is tightly coupled to changes in intracellular iron concentrations in both cultured cells and model vertebrate organisms. Cells in vertebrate organisms respond to excess iron chiefly by post-transcriptional mechanisms. Factors that modulate the effect of iron on ferritin expression are cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), nitric oxide (NO), and oxidative agents. Cytokines such as IL-1β modulate the expression of ferritin in the presence of iron. The regulation is accomplished both by transcriptional and translational mechanisms. There have been numerous reports demonstrating that the effect of ferritin iron-responsive element (IRE) on the iron inducibility of heterologous open reading frames is not as potent as on that of endogenous ferritin mRNAs. The difference in inducibility is accounted for by sequences downstream from the IRE and probably within the ferritin open reading frame (ORF). However, mRNAs that contain the ferritin ORF but lack IRE have little or no iron inducibility. This indicates a requirement for iron-responsive protein (IRP) to bind the IRE, and this interaction serves as the fundamental iron-responsive component of the translational regulatory system for ferritin.

Congenital Heart Disease Linked to Maternal Autoimmunity against Cardiac Myosin

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti–β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal–fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Development of a Mitochondrial 12S rDNA Analysis for Distinguishing Sciuridae Species With Potential to Transmit Ehrlichia and Borrelia Species to Feeding Amblyomma americanum (Acari: Ixodidae)

ABSTRACT Unique oligonucleotide probes were synthesized to distinguish among closely related vertebrate mitochondrial rDNA sequences present in residual bloodmeals in emergent Amblyomma americanum (L.) (Acari: Ixodidae) nymph life-stage ticks. Use of these probes enabled the identification of the Eastern gray squirrel as an important bloodmeal source in nymphs harboring Ehrlichia and Borrelia species. These results were confirmed by identifying these same bacterial genera in Eastern gray squirrel tissues.

Maternal β-Hemolytic Streptococcal Pharyngeal Exposure and Colonization in Pregnancy

Objectives. To report the pharyngeal colonization rate of β-hemolytic streptococci and changes in the value of antistreptolysin O (ASO) and anti-DNase B serology titers during pregnancy. Methods. Healthy pregnant women were recruited and blood was drawn in each trimester. The upper limit of normal (ULN) values for ASO and anti-DNase B was calculated for each trimester. Throat swabs were collected for culture and positive cultures were further assessed for the identification of serogroup of the isolated β-hemolytic streptococcus. Results. Out of a total of 126 pregnant women, 34.1% had positive throat cultures. Group C and group G strains were isolated in 18.2% of throat cultures while group F was detected in 13.5% of cases. The rate of colonization with GAS was 1.6%. There was an overall drop in ASO titer during pregnancy while anti-DNase B titers remained relatively unchanged. ULN values of 164IU, 157IU, and 156IU were calculated for ASO at the first, second, and third trimesters, respectively. Based on the ULN values, 28.6% of patients had recent streptococcal exposure. Conclusions. These results show that pregnant women act as a reservoir for spreading potentially immunogenic (groups C and G) and disease producing (group F) virulent strains of streptococci.

Mechanisms for Induction and Rerepression of Ferritin Synthesis

An iron responsive element (IRE) located within the 5′ untranslated region (5′ UTR) of certain mRNAs (e.g., ferritin) serves as a binding site for a class of specific binding proteins [referred to as the iron regulatory proteins (IRPs)] which, when bound to an IRE, repress translation of those mRNAs [reviewed in Leibold and Guo (1992), Melefors and Hentze (1993), Klausner et al. (1993), Munro (1993), Theil (1993), Mascotti et al. (1995)]. Binding of an IRP to an IRE located proximally to the 5′ end of an mRNA is believed to prevent access of eIF-4F (the cap binding protein) to the 5′ cap structure, resulting in a blockage of initiation (Goossen et al. 1990; Bhasker et al. 1993; Gray and Hentze 1994). When chelatable iron levels are increased in the cell, an IRP is induced to dissociate from the IRE and allow initiation of translation of ferritin [reviewed in Leibold and Guo (1992), Melefors and Hentze (1993), Klausner et al. (1993), Munro (1993), Theil (1993)]. Messages that contain functional IREs in their 5′ UTRs code for ferritin (Leibold and Guo 1992; Melefors and Hentze 1993; Klausner et al. 1993; Munro 1993; Theil 1993), erythroid δ-aminolevulinic acid synthase (δ-ALAS) (Cox et al. 1991; Bhasker et al. 1993), mitochondrial aconitase (m-acon) (Dandekar et al. 1991), Drosophila melanogaster succinate dehydrogenase (Kohler et al. 1995; Gray et al. 1996), and possibly transferrin (Tf) (Cox and Adrian 1993; Cox et al. 1995).