Biology subjects

Kirsebom, L. A.

Publications and source records attributed to Kirsebom, L. A..

3 recordsLinked to original sources

bioRxiv2026

Loss of Mycobacterium marinum ESX-1 genes increase transcription of ESX-6 genes

Mycobacteria form rough and smooth colonies. The Mycobacterium marinum strain 1218S is a smooth colony forming variant isolated from the 1218R strain, which forms rough colonies and is more virulent than 1218S in infecting fish. Genes for the type VII secretion ESX-1 system, which includes mycobacterial virulence genes, have been partially duplicated in M. marinum and is refered to as ESX-6. We recently reported that several ESX-1 genes are missing in the 1218S strain. On the basis of the complete genomes of these two and three other M. marinum strains we provide insight into strain differences and similarities focusing on 1218R and 1218S, and ESX genes, selected virulence genes, and LOS genes, which are involved in lipooligosaccharide synthesis and smooth colony formation. We provide RNA-Seq data for 1218R and 1218S and two other well-characterized M. marinum strains suggesting that loss of ESX-1 genes in 1218S results in increased transcript levels of ESX-6 genes. Furthermore, while there is no difference in gene synteny and sequence of LOS genes comparing 1218R and 1218S, with the exception of duplication of lsr2, a regulator of LOS genes, in 1218S. Our RNA-Seq data show increased transcript levels of LOS genes in stationary 1218S cells relative to 1218R indicating that transcription and/or RNA degradation of LOS genes influence smooth and rough colony formation. We finally provide data suggesting that Ms1 RNA affect the transcription of LOS genes (and ESX-1 genes), and that loss of ESX-1 genes influence biofilm formation.

microbiology↗

bioRxiv2026

The mycobacterial selenocysteine machinery: presence and expression

The Mycobacterium genus includes more than 190 species that occupies diverse ecological niches. Some are nonpathogenic and environmental, whereas others cause severe diseases both in humans and animals, e.g. tuberculosis (TB) and leprosy. SelenoCysteine (SeC) is present in all three domains of life. Here we report the presence of the SeC-machinery (selA, selB, selC and selD) genes and selenoprotein (fdhA) genes in roughly 40% of 244 mycobacterial genomes. Their presence is distributed evenly among slow and rapid growing mycobacteria and our data indicate that they were acquired through horizontal gene transfer. Some mycobacteria however lost these genes during the evolution of the genus. We provide RNA-Seq data showing transcript levels of the SeC-machinery genes and fdhA in different mycobacteria grown under different conditions. Finally, we suggest that selC (the tRNASeC gene), positioned immediately upstream of selA-selB, is involved in the regulation of the expression of the SeC-machinery genes selA-selB. Together our data expand our understanding of selenocysteine metabolism and its evolution within the Mycobacterium genus.

molecular biology↗

bioRxiv2023

Suppression of the E. coli rnpA49 conditionally lethal phenotype via different compensatory mutations

RNase P is an essential enzyme found across all domains of life that is responsible for the 5-end maturation of precursor tRNA transcripts. Since its discovery in the 1970s, numerous studies have sought to elucidate the mechanisms and biochemistry governing RNase P function. However, much remains unknown about the regulation of RNase P expression, the turnover and degradation of the enzyme, and the mechanisms underlying the phenotypes and complementation of specific RNase P mutations. In Escherichia coli, the temperature-sensitive rnpA49 mutation in the protein subunit of RNase P has arguably been one of the most well-studied and commonly used mutations for examining the enzymes activity in vivo. Here we report for the first time naturally-occurring temperature-resistant suppressor mutations of E. coli strains carrying the rnpA49 allele. We find that rnpA49 strains can partially compensate the temperature-sensitive defect via gene amplifications of either RNase P subunit (rnpA49 or rnpB) or by the acquisition of loss-of-function mutations in Lon protease or RNase R. Our results agree with previous plasmid overexpression and gene deletion complementation studies and importantly suggest the involvement of Lon protease in the degradation and/or regulatory pathway(s) of the mutant protein subunit of RNase P. This work offers novel insight into the behavior and complementation of the rnpA49 allele in vivo and provides direction for follow-up studies regarding RNase P regulation and turnover.

evolutionary biology↗