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Gautam, B.

Publications and source records attributed to Gautam, B..

4 recordsLinked to original sources

Diabetes mellitus affects urinary tissue tropism of group B streptococci in a sex-dependent manner

Diabetes mellitus (DM) increases susceptibility to Streptococcus agalactiae (group B Streptococcus or GBS) urinary tract infections (UTI) and their exacerbations such as ascending pyelonephritis and sepsis, although underlying molecular mechanisms have not been fully deciphered. To address our hypothesis that DM mediated alterations in the host urinary immune defenses increase susceptibility to GBS-UTI, we inoculated, via transurethral route, GBS strain 10/84 into the urinary bladders of 8 weeks old, male and female, diabetic (obese, hyperglycemic mice denoted as D) and non-diabetic (ND) mouse littermates. At 24 h post-infection (hpi), compared to their ND littermates, the D-mice showed significantly higher GBS CFUs in the bladder, the kidneys, and the spleen. This was accompanied by a significantly reduced recruitment of CD45+ leukocytes to and suppression of pro-inflammatory cytokine production in GBS-infected D-bladder and D-kidneys compared to their ND counterparts. We also noted sex-dependent differences in GBS urinary tissue tropism. For example, D-females exhibited significantly higher bladder burden compared to ND-females, D-males, and to ND-males, while the bladder burden in ND-females was not significantly different from that in ND-males. In contrast, ND-males showed significantly higher kidney CFUs than ND-females and DM further increased kidney CFU burden in males. GBS-induced recruitment of CD45+ leukocytes was not different between male and female mice within either D or ND cohorts. GBS-UTI induced significantly higher CXCL1 production in male bladders in both D and ND cohorts compared to their female counterparts. These results indicate that DM increases susceptibility to GBS-UTI and the dissemination to spleen by affecting leukocyte recruitment and pro-inflammatory cytokine production in a sex-dependent manner. ImportanceIn this study we sought to understand why diabetic individuals are more susceptible to urinary tract infections (UTI) by Gram positive Streptococcus agalactiae (group B Streptococcus or GBS). We induced UTI by inoculating GBS into the bladders of diabetic (obese, hyperglycemic) and non-diabetic, male and female mice. At 24 hours after infection, compared to the non-diabetic mice, the diabetic mouse urinary tracts showed higher GBS counts and reduced immune defenses. Diabetes also promoted dissemination of GBS to the spleen. Furthermore, female diabetic mice were more susceptible to bladder infection while diabetes worsened the increased overall susceptibility of males to kidney infection, a difficult-to-treat, potentially life threatening exacerbation of GBS-UTI. Overall, our results suggest that both diabetes and sex are important determinants of susceptibility to GBS-UTI and resulting severe outcomes.

microbiology↗

Population and adaptation history of 739 Thlaspi arvense natural accessions

Pennycress (Thlaspi arvense) is a promising intermediate oilseed crop, producing oil suitable for conversion to biofuels--including aviation fuels. While domestication efforts are ongoing, a deeper understanding of the genetic architecture of traits is crucial for informing future breeding efforts. Here, we conducted the largest genomic and phenotypic survey of pennycress to date, analyzing 739 accessions collected across four continents. Leveraging whole-genome sequencing and field-collected phenotypes, we characterized the standing genetic variation underlying key agronomic traits and climate resilience. Our findings revealed multiple independent migration events to North America, with substantial genetic admixture. We identified homologs of Arabidopsis thaliana flowering-time genes that contribute to adaptation and demonstrated the agronomic benefits of winter-type pennycress. Furthermore, through multi-season field trials, we identified a genomic region containing a cluster of mTERF genes strongly associated with green canopy coverage, a critical trait for biomass retention and yield stability. These insights provide a genomic roadmap for accelerating pennycress domestication and improving its resilience to climate variability.

genomics↗

Creating a new oilseed crop, pennycress, by combining key domestication traits using CRISPR genome editing

Considerable offseason farmland lays fallow because there are few crops that can profitably fit between primary crops. To remedy, we employed CRISPR genome editing to the freeze-tolerant, rapid cycling wild Brassica, Thlaspi arvense L. (field pennycress). High-yielding domesticated pennycress varieties were created having seed compositions comparable to "double low" canola (low erucic acid and glucosinolate). Seed glucosinolate content was reduced 75 % by combining mutations in R2R3-MYB (MYB28) and bHLH MYC (MYC3) transcription factors. Pennycress weediness was greatly reduced by knockout of the bHLH transcription factor TRANSPARENT TESTA8 (TT8), lowering seed dormancy and seed coat protections thereby mitigating pennycress re-emergence in fields. Domesticated pennycress offers farmers a profitable, low-carbon-intensity intermediate crop that confers ecosystem benefits while producing grain for renewable fuels and enhanced food security.

genetics↗

A pennycress transparent testa 8 knockout mutant has drastic changes in seed coat anatomy and chemical compositions

Pennycress is a winter annual intermediate crop with approximately 30% seed oil content suitable for producing biofuels. Here, we evaluated seed development, anatomy, and agronomically relevant traits of a transparent testa 8 knockout mutant (tt8-2bp) generated by CRISPR genome editing to improve seed quality. We performed histochemical analyses on wild-type and tt8-2bp seeds at different developmental stages. No visible anatomical defects were observed in embryos and endosperm of tt8-2bp seeds. However, tt8-2bp seed coats completely lost proanthocyanidins which were accumulated in an inner integument cell layer and in the thickened cell wall of an outer integument cell layer of wild-type seed coats. Based on spatial metabolomic and solid-state NMR analyses, tt8-2bp seed coats had decreased aromatic compounds and cell wall polysaccharides compared to wild-type seed coats. Additionally, tt8-2bp seeds had reduced seed coat dry weights and increased embryo dry weights compared to wild-type seeds, indicating changes in macronutrient partitioning during seed development. Mature tt8-2bp seeds exhibited increased imbibition rates and seed coat permeability to water-soluble molecules, suggesting a higher seed coat hydrophilicity than wild-type seeds. In conclusion, we did not find defects in tt8-2bp mutant seeds that were unfavorable agronomically, supporting that TT8 is an attractive target for pennycress domestication. HighlightHistochemical analyses of pennycress seeds revealed a complete loss of proanthocyanidins in tt8-2bp seed coats accompanied by increased seed imbibition rates and seed coat permeability compared to wild-type seeds.

plant biology↗