Biology subjects

Fritz, S. A.

Publications and source records attributed to Fritz, S. A..

6 recordsLinked to original sources

bioRxiv2026

Antibody Correlates of Resilience to Staphylococcus aureus Disease and Recurrence in Children

Staphylococcus aureus remains a major global pathogen with no licensed vaccine and high recurrent infection burden, yet correlates of protection remain undefined. In a prospective pediatric cohort, we profiled 319 children spanning non-carriers, asymptomatic carriers, those with skin and soft tissue infection (SSTI), or invasive disease. We interrogated 182,149 antibody features, generating the most comprehensive S. aureus immune profiling dataset to date. Antibody responses increased with age, marked by expansion of IgG subclasses and Fc-receptor engagement. Asymptomatic carriage was associated with functional antibody profiles targeting conserved surface antigens and select toxins. Multivariate modeling robustly distinguished clinical phenotypes and identified high-value antigens associated with disease resilience. Protection from recurrent disease converged on enhanced Fc{gamma}R binding and antibody effector function. These findings nominate key antigen targets, and highlight anti-Hla neutralizing antibodies and functional antibodies to additional surface antigens that can be recapitulated through Fc engineering, informing next-generation vaccine and monoclonal antibody strategies.

immunology↗

bioRxiv2025

Red List criteria underestimate climate-related extinction risk of range-shifting species

Climate change causes global species redistribution and elevates extinction risk, making early identification of vulnerable species critical for timely conservation. The IUCN Red List provides guidelines for assessing climate-related extinction risk using species distribution models (SDMs) and spatially explicit population models (SEPMs). However, a systematic evaluation of these guidelines is currently missing. Using simulations of virtual species with diverse life-history traits and range dynamics, we found that SDMs consistently underestimated extinction risk for range-shifting species. This was due to a concave relationship between population size and habitat loss, which contradicts the linear assumption in the Red List guidelines. For range-contracting species, SDMs provided adequate warning times. Probabilistic extinction estimates from SEPMs provided delayed warning for all species, particularly for highly threatened ones. Our results reveal key limitations of current Red List guidelines under climate change. Based on our findings, we provide tentative recommendations for updating the IUCN Red List guidelines.

ecology↗

bioRxiv2024

Trophic adaptation of large terrestrial omnivores to global change

Large omnivores at the top of food webs play a key role in ecosystems, as their ability to feed on multiple trophic levels stabilizes food-web dynamics and impacts ecosystem functioning. However, it is largely unexplored how large omnivores adapt their trophic interactions to altered resource availability under global change, particularly in terrestrial ecosystems. Here, we combine macroecological and paleoecological approaches and reveal that extant bears, the largest terrestrial omnivores, adapt their trophic position in food webs dynamically to net primary productivity and growing season length. Throughout their geographic ranges, extant bears occupy higher trophic positions in unproductive ecosystems with short growing seasons than in productive ecosystems with long growing seasons. Consistent with this geographic pattern, the trophic position of the brown bear sharply decreased at the transition from the Late Pleistocene to the Holocene, coinciding with an increase in net primary productivity and growing season length. These findings demonstrate that trophic interactions of omnivores are not static but change dynamically in response to environmental change. Our findings suggest that global change impacts on primary production and vegetation seasonality may trigger shifts in the functional role of omnivores, with consequences for food webs and ecosystem functions. Significance statementLarge omnivores play a key role in ecosystems, as they stabilize food-web dynamics and impact ecosystem functioning. However, how omnivores adapt their trophic interactions to changes in resource availability under global change remains unexplored. Combining macroecological and paleoecological approaches, we show that extant bears, the largest terrestrial omnivores, occupy lower trophic positions in food webs as net primary productivity and growing season length increase. This trophic adaptation is evident across the geographic ranges of all extant terrestrial bear species and for brown bears at the transition from the Late Pleistocene to the Holocene. Therefore, impacts of global change on primary production and vegetation seasonality may trigger shifts in the functional role of omnivores, with consequences for food webs and ecosystems. One sentence summaryGlobal changes in primary productivity and vegetation seasonality alter the functional role of large omnivores in terrestrial ecosystems.

ecology↗

bioRxiv2022

How to resolve conflicting conservation objectives: A decision support tool for the global selection of multi-purpose protected areas

The establishment and maintenance of protected areas (PAs) is viewed as a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting protected areas based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences, as well as real-time comparison of the selected areas that result from such different priorities. We apply the tool across 1347 terrestrial PAs and highlight frequent trade-offs among different objectives, e.g., between species protection and ecosystem integrity. Outputs indicate that decision makers frequently face trade-offs among conflicting objectives. Nevertheless, we show that transparent decision-support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.

ecology↗

bioRxiv2021

Global plant-frugivore trait matching is shaped by climate and biogeographic history

Species interactions are influenced by the trait structure of local multi-trophic communities. However, it remains unclear whether mutualistic interactions in particular can drive trait patterns at the global scale, where climatic constraints and biogeographic processes gain importance. Here we evaluate global relationships between traits of frugivorous birds and palms (Arecaceae), and how these relationships are affected, directly or indirectly, by assemblage richness, climate and biogeographic history. We leverage a new and expanded gape size dataset for nearly all avian frugivores, and find a positive relationship between gape size and fruit size, i.e., trait matching, which is influenced indirectly by palm richness and climate. We also uncover a latitudinal gradient in trait matching strength, which increases towards the tropics and varies among zoogeographic realms. Taken together, our results suggest trophic interactions have consistent influences on trait structure, but that abiotic, biogeographic and richness effects also play important, though sometimes indirect, roles in shaping the functional biogeography of mutualisms.

ecology↗

bioRxiv2019

Potent, specific MEPicides for treatment of zoonotic staphylococci

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact, zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius. A series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM were synthesized, and data indicate that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci, but also bypassed the need for GlpT-mediated cellular transport. Collectively, our data indicate that the prodrug MEPicides selectively and robustly inhibit DXR in zoonotic staphylococci, and further, DXR represents a promising, druggable target for future development.\n\nAuthor SummaryThe proliferation of microbial pathogens resistant to the current pool of antibiotics is a major threat to public health. Drug resistance is pervasive in staphylococci, including several species that can cause serious zoonotic infections in humans. Thus, new antimicrobial agents are urgently need to combat these life-threatening, resistant infections. Here we establish the MEP pathway as a promising new target against zoonotic staphylococci. We determine that fosmidomycin (FSM) selectively targets the isoprenoid biosynthesis pathway in zoonotic staphylococci, and use forward genetics to identify the transporter that facilitates phosphonate antibiotic uptake. Employing this knowledge, we synthesized a series of potent antibacterial prodrugs that circumvent the transporter. Together, these novel prodrug inhibitors represent promising leads for further drug development against zoonotic staphylococci.

microbiology↗