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Numerous factors are contributing to the loss of biodiversity. These include complex effects of multiple abiotic and biotic stressors that may drive population losses. These losses are especially illustrated by amphibians, whose populations are declining worldwide. The causes of amphibian population declines are multifaceted and context-dependent. One major factor affecting amphibian populations is emerging infectious disease. Several pathogens and their associated diseases are especially significant contributors to amphibian population declines. These include the fungi Batrachochytrium dendrobatidis and B. salamandrivorans, and ranaviruses. In this review, we assess the effects of these three pathogens on amphibian hosts as found through experimental studies. Such studies offer valuable insights to the causal factors underpinning broad patterns reported through observational studies. We summarize key findings from experimental studies in the laboratory, in mesocosms, and from the field. We also summarize experiments that explore the interactive effects of these pathogens with other contributors of amphibian population declines. Though well-designed experimental studies are critical for understanding the impacts of disease, inconsistencies in experimental methodologies limit our ability to form comparisons and conclusions. Studies of the three pathogens we focus on show that host susceptibility varies with such factors as species, host age, life history stage, population and biotic (e.g., presence of competitors, predators) and abiotic conditions (e.g., temperature, presence of contaminants), as well as the strain and dose of the pathogen, to which hosts are exposed. Our findings suggest the importance of implementing standard protocols and reporting for experimental studies of amphibian disease.

Parasites and pathogens are often aggregated in a minority of susceptible hosts within a population, with a majority of individuals harboring low infection intensities. However, determining the relative importance of host traits to explain this heterogeneity is a challenge. One ecologically important pathogen is Batrachochytrium dendrobatidis (Bd), which causes the disease chytridiomycosis and has been associated with many amphibian population declines worldwide. For many hosts, post-metamorphic stages are generally more susceptible than the larval stage. Yet, examination of the effects of Bd infection at different ages within a life stage, has received little attention. This study investigated the hypothesis that recently-post-metamorphic frogs were more sensitive to chytridiomycosis than older frogs, and that sensitivity to Bd infection decreased as frogs aged. We examined this relationship with Pacific treefrogs (Pseudacris regilla) and red legged frogs (Rana aurora). Age had a strong effect on susceptibility to infection, infection intensity, and survival-but not in the directions we had predicted. In both host species, an increase in age was associated with frogs becoming more susceptible to Bd infection, harboring larger infection intensities, and greater risk of mortality. This suggests that the timing of Bd exposure may influence amphibian population dynamics.

Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing.