Biology subjects

LaFayette, C.

Publications and source records attributed to LaFayette, C..

2 recordsLinked to original sources

bioRxiv2024

MOB rules: Antibiotic Exposure Reprograms Metabolism to Mobilize Bacillus subtilis in Competitive Interactions

Antibiotics have dose-dependent effects on exposed bacteria. The medicinal use of antibiotics relies on their growth-inhibitory activities at sufficient concentrations. At subinhibitory concentrations, exposure effects vary widely among different antibiotics and bacteria. Bacillus subtilis responds to bacteriostatic translation inhibitors by mobilizing a population of cells (MOB-Mobilized Bacillus) to spread across a surface. How B. subtilis regulates the antibiotic-induced mobilization is not known. In this study, we used chloramphenicol to identify regulatory functions that B. subtilis requires to coordinate cell mobilization following subinhibitory exposure. We measured changes in gene expression and metabolism and mapped the results to a network of regulatory proteins that direct the mobile response. Our data reveal that several transcriptional regulators coordinately control the reprogramming of metabolism to support mobilization. The network regulates changes in glycolysis, nucleotide metabolism, and amino acid metabolism that are signature features of the mobilized population. Among the hundreds of genes with changing expression, we identified two, pdhA and pucA, where the magnitudes of their changes in expression, and in the abundance of associated metabolites, reveal hallmark metabolic features of the mobilized population. Using reporters of pdhA and pucA expression, we visualized the separation of major branches of metabolism in different regions of the mobilized population. Our results reveal a regulated response to chloramphenicol exposure that enables a population of bacteria in different metabolic states to mount a coordinated mobile response.

microbiology↗

bioRxiv2021

Evolutionarily conserved genetic interactions between nphp-4 and bbs-5 mutations exacerbate ciliopathy phenotypes

Primary cilia are sensory and signaling hubs with a protein composition that is distinct from the rest of the cell due to the barrier function of the transition zone (TZ) at the base of the cilium. Protein transport across the TZ is mediated in part by the BBSome, and mutations disrupting TZ and BBSome proteins cause human ciliopathy syndromes. Ciliopathies have phenotypic variability even among patients with identical genetic variants, suggesting a role for modifier loci. To identify potential ciliopathy modifiers, we performed a mutagenesis screen on nphp-4 mutant C. elegans and uncovered a novel allele of bbs-5. Nphp-4;bbs-5 double mutant worms have phenotypes not observed in either individual mutant strain. To test whether this genetic interaction is conserved, we also analyzed zebrafish and mice mutants. While Nphp4 mutant zebrafish appeared overtly normal, Bbs5 mutants exhibited scoliosis. When combined, Nphp4;Bbs5 double mutant zebrafish did not exhibit synergistic effects, but the lack of a phenotype in Nphp4 mutants makes interpreting these data difficult. In contrast, viable Nphp4;Bbs5 double mutant mice were not obtained and there were fewer mice than expected carrying three mutant alleles. Additionally, postnatal loss of Bbs5 in mice using a conditional allele compromised survival when combined with a Nphp4 allele. As cilia are formed in the double mutant mice, the exacerbated phenotype is likely a consequence of disrupted ciliary signaling. Collectively, these data support an evolutionarily conserved genetic interaction between Bbs5 and Nphp4 alleles that may contribute to the variability in ciliopathy phenotypes.

genetics↗