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Tanner, H.

Publications and source records attributed to Tanner, H..

3 recordsLinked to original sources

Nutrient-deprived growth of streptomycetes reveals a novel growth phenotype with enhanced antimicrobial activity

Species of the genus Streptomyces are filamentous bacteria mainly residing in soils. The capacity of streptomycetes to adapt to various environments is reflected in the sheer size of their genomes and the number of encoded regulatory proteins. The nutrient-rich laboratory conditions used for culturing significantly differ from the conditions in the natural habitat of streptomycetes and fail to stimulate their full range of adaptive behaviors; as on of the results, the majority of biosynthetic gene clusters remain silent. Moreover, the use of rich media has led to the assumption that nutrient depletion ultimately promotes sporulation. However, we demonstrate that S. coelicolor colonies can respond to nutrient depletion by displaying a previously unidentified phenotypic transition termed "foraging" due to its submerged and continuous growth on depleted media. The foraging phenotype is distinctly different from conventional phenotypes in terms of colony morphology, genomic stability, and metabolomic profile. This adaptation to nutrient deprivation through foraging is found throughout the Streptomyces phylogeny, indicating that the phenotype is highly conserved. Furthermore, foraging S. coelicolor gains the ability to inhibit molds and enhanced competitive activity against both gram-negative and gram-positive bacteria is detected in other species. These findings highlight how morphological adaptations of streptomycetes in nutrient-limited environments alter secondary metabolite production, enabling the screening of novel antimicrobial activities. These discoveries have implications ranging from the basic biology of streptomycetes to drug discovery and microbial ecology.

microbiology↗

Bile acids accumulate norovirus-like particles and enhance binding to and entry into human enteric epithelial cells

Human norovirus (HuNoV) is a leading cause of acute viral gastroenteritis, but despite high impact on public health and health care, the mechanisms of viral attachment to and entry into target cells are not yet fully understood. It is well known that body fluids such as blood can transmit unrelated viruses, but recent reports also indicate that saliva and bile contribute to transmission of HuNoV. For example, human bile acids increase cell surface ceramide levels in human enteroids, which improves norovirus entry into cells resulting in enhanced replication. Bile acids can also interact directly with the norovirus capsid, but it is not known whether bile or other gastrointestinal body fluids directly affect HuNoV attachment to host cells. In this study, we investigated the effects of patient-derived gastric juice, pancreatic juice, and bile on HuNoV GII.4 virus-like particle (VLP) attachment to and entry into a human duodenal cell line, HuTu-80. We show that while gastric juice and pancreatic juice do not affect viral attachment or entry, bile - in particular hydrophobic bile acids - significantly enhance cellular attachment and subsequent entry of GII.4 VLPs into cells. In addition, we show that hydrophobic bile acids induce accumulation of viral particles in the vicinity of cells. Our results suggest the presence of a new en masse infection mechanism, where bile acids aggregate virions, and allow direct and more efficient attachment to and entry into target cells. ImportanceViruses transmitted by the fecal-oral route encounter secreted host factors in gastrointestinal fluids. Some host factors can be exploited by the virus to facilitate infection. Human bile acids indirectly promote norovirus entry into and infection of human enteroids, but the direct effect of bile acids on attachment and uptake, along with the impact of other gastrointestinal fluids, remain unknown. Here, we investigated the direct effects of human body fluids on cellular attachment of norovirus VLPs. We show that human bile and hydrophobic bile acids induce an accumulation of norovirus VLPs, which is associated with significantly enhanced attachment and entry into human duodenal cell lines. These results highlight the differential effects of gastrointestinal body fluids on viral attachment and entry, while providing useful information into the complex HuNoV-host interactions that facilitate infection.

microbiology↗

Altered germline cyst and oocyte differentiation in Tex14 mutant mice reveal a new mechanism underlying female reproductive life-span

In adult mammalian females, primordial follicles that form in the fetal/neonatal ovary are the only source to sustain adult ovarian function. Our previous studies revealed that during oocyte differentiation and primordial follicle formation in mouse fetal ovaries, primary oocytes form via gaining cytoplasm and organelles from sister germ cells that are connected to them by intercellular bridges within germline cysts. To better understand the role of intercellular bridges in oocyte differentiation, we analyzed mutant females lacking testis-expressed 14 (Tex14), a gene involved in cytokinesis and bridge formation. In Tex14-/- fetal ovaries, germ cells divide to form a reduced number of cysts in which sister germ cells are still connected via syncytia or fragmented cell membranes, rather than normal intercellular bridges. Compared with wildtype cysts, Tex14-/- cysts fragment at a higher frequency and produce a greatly reduced number of primary oocytes with highly precocious cytoplasmic enrichment and enlarged volume. By contrast, Tex14+/- germline cysts are less fragmented and generate primary oocytes that are smaller than wild type. Interestingly, enlarged Tex14-/- primary oocytes are much more stable than wild type oocytes and more efficiently sustain folliculogenesis, whereas undersized Tex14+/- primary oocytes turn over at an accelerated rate. Our observations directly link the nature of fetal germ cell connectivity to cytoplasmic enrichment during oocyte differentiation and to oocyte developmental potential in the adult ovary. Our results imply that the duration of adult ovarian function is strongly influenced by the number of primary oocytes acquiring highly enriched cytoplasm during oocyte differentiation in fetal ovaries, rather than just by the size of the primordial follicle pool.

developmental biology↗