Biology subjects

Bhowmik, N.

Publications and source records attributed to Bhowmik, N..

3 recordsLinked to original sources

bioRxiv2026

Siderophore-Mediated Competition Between Cystic Fibrosis Pathogens Increases Virulence Factor Production

The airways of people with cystic fibrosis (CF) are colonized by a polymicrobial community and coinfections with multiple pathogens may exacerbate disease. By analyzing 16S rRNA gene sequencing datasets, we determined that Achromobacter-Pseudomonas coinfection was associated with worse lung function than infection with either pathogen alone, or coinfections with Pseudomonas and other CF bacterial pathogens. We discovered Achromobacter spp. induced production of the siderophore pyoverdine by Pseudomonas aeruginosa strain PAO1 and other clinical isolates on synthetic CF sputum medium (SCFM), supplemented with physiologically relevant iron concentrations. We then tested 21 Achromobacter strains, encompassing seven species, and determined that 17 (81%) induced pyoverdine production. We sequenced the full genomes of these Achromobacter and found 18 (86%) encoded a biosynthetic gene cluster for the production of alcaligin. This compound is an iron-chelating siderophore that has previously been shown to be involved in colonization of the respiratory tract by Bordetella spp. Using mass spectrometry imaging, we confirmed that Achromobacter dolens strain RMS0405 produces alcaligin during coculture with PAO1. Further, we found that supplementing SCFM with increasing iron abolishes pyoverdine induction by PAO1 during coculture. Pyoverdine is known to contribute directly to virulence and regulate expression of other virulence factors. Using transcriptomics and proteomics, we determined that RMS0405 induces a low-iron stress response in PAO1 and stimulates the production of exotoxin A and other known virulence factors. Together, our results indicate that Achromobacter spp. and P. aeruginosa may exacerbate virulence in the airways of people with CF as a byproduct of competition for iron.

microbiology↗

bioRxiv2026

Differential Metabolite Production Underlies Disruption of the Cystic Fibrosis Airway Microbiota by Pathogens

Cystic fibrosis (CF) is a multisystem disease characterized by the accumulation of mucus in the airways that promotes pathogen colonization, leading to respiratory exacerbations, lung failure, and death. Culture-independent approaches have revealed that the CF airway harbors a complex microbiota, including opportunistic pathogens and bacteria that colonize the oropharynx. Here, we reanalyzed 5,260 16S rRNA gene microbiota datasets to infer ecological associations between members of the CF microbiota. We determined that pathogens are more likely to proliferate and dominate when present, while oropharyngeal bacteria are more likely to form persistent communities. Further, we found higher diversity and increasing numbers of inferred interactions were positively associated with lung function. In contrast, pathogens were negatively associated both with each other and with oropharyngeal bacteria, suggesting that they may disrupt the microbiota. To validate these predictions, we cultured 1,597 bacterial isolates from 96 people with CF and performed 12,542 coculture assays against eight representative CF pathogenic and oropharyngeal bacteria. 23% of these interactions resulted in growth inhibition. While Pseudomonas isolates were, on average, the most inhibitory, we observed variable activity among isolates. We then confirmed that Pseudomonas aeruginosa isolates, even those from the same donor and timepoint, exhibited significant differences in their metabolome and bioactivity profiles that correlated with acquisition of mutations. Together, our results suggest that pathogens may disrupt the CF microbiota and bloom in part through differential metabolite production. Furthermore, these data highlight that characterizing multiple isolates is necessary to capture the full landscape of chemically mediated interactions within microbial communities. ImportanceThe cystic fibrosis (CF) airway harbors a complex microbiota, including oropharyngeal bacteria and opportunistic pathogens that establish chronic infections and cause lung failure. We confirmed that microbiota diversity is correlated with health and that a pathogen-dominated microbiota is associated with reduced lung function. We then inferred microbial interactions, which suggested that pathogens are able to disrupt the microbiota. To validate these predictions, we cultured bacterial isolates from people with CF and performed thousands of coculture assays, finding that approximately one-quarter of interactions resulted in growth inhibition. Pseudomonas broadly inhibited other members of the CF airway microbiota. However, we observed marked variability in bioactivity and metabolite profiles of Pseudomonas aeruginosa isolates, even from the same donor at the same time. Our results suggest that pathogens disrupt the CF microbiota, possibly through bioactive metabolite production, and that characterizing multiple isolates is necessary to capture the complete picture of interactions in these communities.

microbiology↗

bioRxiv2025

An atlas of cell type specific regulatory effects in cattle

Understanding the genetic and molecular architecture of complex traits and artificial selection is crucial for advancing sustainable precision breeding in cattle and other livestock. Yet, how genetic variation affects cellular gene expression remains elusive in cattle. Here, by integrating 8,866 bulk RNA-seq samples and 999,192 single cells of 81 cell types in 22 bovine tissues, we presented a comprehensive atlas of regulatory variants at the cell type resolution in cattle. By colocalizing with bulk-tissue expression quantitative trait loci (beQTL), we detected 57,043 novel cell-type stratified eQTL and cell-type/state interaction eQTL in 18,153 genes, which also exhibited a stronger tissue/cell-type specificity than beQTL. By examining genome-wide associations (GWAS) of 44 complex traits, these cell-resolved eQTL were colocalized with 505 (24%) additional GWAS loci compared to beQTL. Through integrating this resource with selection signatures between dairy and beef cattle, we provided tissue/cell-specific regulatory insights into cattle breeding. Overall, the current atlas of cell-type-specific regulatory variants will serve as an invaluable resource for cattle genomics and selective breeding.

genetics↗