Biology subjects

Tucker, S. K.

Publications and source records attributed to Tucker, S. K..

2 recordsLinked to original sources

bioRxiv2025

Experimental infections reveal unexceptional viral tolerance in bats

A common explanation for bats being a conspicuous source of zoonotic viruses is their purported ability to coexist with viruses without suffering overt disease. This belief has catalyzed the discovery of unique features of bat immune systems which may have translational value as broad-spectrum antivirals, particularly if they evolved as a byproduct of bats' unique life history rather than through conventional co-evolutionary processes. Surprisingly, whether bats compared to other host groups suffer less disease from co-evolved viruses or from viruses generally has not been formally assessed. Here, synthesizing eighty-six years of experimental infections, involving 54 viruses, 85 host species, and over 5,600 animals, we document disease in bats following inoculation by taxonomically diverse viruses, including ones that are relatively benign in humans. The occurrence of overt disease, the likelihood of mortality, and the severity of disease in bats were indistinguishable from those experienced by rodents, another group associated with many zoonotic viruses. These patterns were consistent when considering only bat-associated viruses inoculated into bats and rodent-associated viruses inoculated into rodents and among inoculations which lacked shared co-evolutionary history. Instead, disease outcomes following infection were shaped by experimental design, viral host range, and evolutionary context. Unexceptional disease in bats from novel or co-evolved infections suggests that order-level host life history traits such as flight have inconsistent consequences for antiviral immunity and highlights the need to evaluate the functional properties of putatively unique features of bat immunity in vivo. These results do not exclude the possibility of developing broader-acting or more potent antivirals from bat immune systems nor do they diminish the potential value of mechanistic insights into bat immunity. However, they do not support the premise underlying the idea that bats will be an unusually rich source of future biomedical breakthroughs.

evolutionary biology↗

bioRxiv2024

Aurodox, a polyketide from Streptomyces goldiniensis, inhibits transcription of the type III secretion system of multiple Gram-negative pathogens

Gram-negative pathogens pose a significant threat due to their propensity for causing various infections, often coupled with formidable resistance to conventional antibiotic treatments. In light of this challenge, the development of antivirulence (AV) compounds emerges as a promising alternative strategy, aiming to disrupt key virulence mechanisms rather than directly targeting bacterial viability. One such compound, aurodox, derived from Streptomyces goldiniensis, has exhibited promising AV properties in our prior studies. Specifically, aurodox caused a marked downregulation in the expression and function of the E. coli type 3 secretion system (T3SS), a needle-like injectosome structure which is deployed to translocate effector proteins from the cytoplasm to the host target cells. However, the broader spectrum of aurodoxs efficacy against T3SS across diverse pathogens remained unanswered, prompting the focus of this work. Using quantitative real-time PCR, we show that aurodox exerts inhibitory effects on selected T3SS in various pathogens, including Salmonella typhimurium, Yersinia pseudotuberculosis, and Vibrio parahaemolyticus. However, aurodox was not a universal blocker of all secretion systems, showing selectivity in its mode-of-action, even within a single strain. This finding was verified using transcriptomics which demonstrated that aurodox selectively blocks the expression of the Salmonella typhimurium SPI-2 type T3SS whilst other pathogenicity islands, including the SPI-1 system were not inhibited. To delve deeper into the mechanisms governing aurodoxs efficacy against these pathogens, we analysed transcriptomic datasets from both E. coli and S. Typhimurium treated with aurodox. By identifying orthologous genes exhibiting differential expression in response to aurodox treatment across these pathogens, our study sheds light on the potential mechanisms underlying the action of this rediscovered antibiotic.

microbiology↗