Biology subjects

Koskiniemi, S.

Publications and source records attributed to Koskiniemi, S..

5 recordsLinked to original sources

bioRxiv2026

OmrA sRNA Inhibits Translation of Phosphoenolpyruvate Carboxylase to Impair TCA-Cycle Flux

Small RNAs (sRNAs) rarely cause strong growth phenotypes upon overexpression, complicating efforts to link regulatory interactions to physiological outcomes. Here, we report that high levels of the Escherichia coli sRNA OmrA, but not its sibling OmrB, severely inhibit growth in glucose minimal medium. Genetic, biochemical, and physiological analyses indicate that OmrA-dependent toxicity results from reduced flux through the tricarboxylic acid (TCA) cycle. A UV-based suppressor screen identified mutations in the gene encoding Hfq, the RNA-chaperone that aids sRNA-mRNA interactions. Secondly, three independent mutations clustered in the ribosome-binding site of ppc, encoding phosphoenolpyruvate carboxylase, a key anaplerotic enzyme. OmrA directly inhibits Ppc translation via Hfq-dependent base-pairing in the ppc 5' UTR, including the mutated nucleotides obtained in the genetic screen. OmrA is significantly more effective than OmrB in ppc repression in vivo and in vitro, consistent with sequence divergence in their central regions. Supplementation with glutamate, glutamine, or downstream TCA cycle metabolites fully restores growth, linking reduced Ppc levels to metabolic limitation. These results identify ppc as a physiologically relevant OmrA target and suggest how RNA toxicity can uncover central metabolic nodes used by sRNAs to modulate bacterial physiology.

microbiology↗

bioRxiv2026

Roles of bacterial growth competition systems in colonization of the murine gut

The gut microbiome is essential for human health. Although the gut microbiota is largely stable at the species level in healthy individuals, strain-level variation remains less understood. Many bacterial strains encode toxin delivery systems that may shape competition within the gut. Here, we investigate how contact-dependent growth inhibition (CDI) and colicins influence intestinal colonization by a competitive murine Escherichia coli isolate, R12. We show that R12 can colonize an intact mouse gut microbiota by displacing resident Enterobacteriaceae, but success depends on multiple interacting factors. CDI systems and colicins provide a competitive advantage against resident E. coli, particularly during early colonization, while metabolic flexibility and access to alternative carbon sources support long-term persistence. Colonization outcomes vary between hosts and are shaped by resident microbiota composition, strain-level competition, and the initial invader-to-resident ratio. Overall, successful gut invasion is determined by the combined effects of bacterial antagonistic systems, metabolic capacity, and ecological context.

microbiology↗

bioRxiv2024

A delivered DNase toxin creates population heterogeneity through transient intoxication of siblings.

Population heterogeneity is important for multicellular behavior and division of labor. Bacterial toxin delivery has been implicated in generating population heterogeneity, but the molecular mechanisms behind this are not well understood. Here we investigate how CdiA toxins generate heterogeneity in isogenic populations. Using a DNase toxin as proxy, we find that E. coli populations able to deliver the toxin show a heterogeneous expression of the SOS-response gene sulA. Heterogeneity results from excessive delivery of toxin into some cells, which become intoxicated due to insufficient immunity. Intoxication is transiently reversible, and intoxicated cells can be rescued by de novo synthesis of cognate immunity protein. Expression of sulA is regulated by both DNA damage and redox status. Interestingly, kin-delivery changes redox status, whereas intoxicated non-kin cells induce the SOS DNA damage response. The former results in changed expression of metabolic genes whereas the latter induces prophage excision, which may promote horizontal gene transfer. In conclusion, we identify a molecular mechanism by which heterogeneity is generated through toxin delivery among kin, and the consequences of said heterogeneity. Significance statementBacteria communicate through secretion of chemical signaling molecules to perform multicellular behavior. Recent advances suggest that contact-mediated toxin delivery allow bacteria to participate also in direct cell-cell communication. How such toxin-mediated communication would work mechanistically is however unclear. Here we elucidate a molecular mechanism of a toxin-mediated communication, where kin-cells transiently intoxicate each other, resulting in physiological changes. These changes depend on the toxic activity, i.e. other toxins with different activities are likely to give rise to other responses. Thus, the arsenal of toxins that a bacterium harbors could affect their ability to communicate. Understanding the molecular mechanism of how toxins could mediate polyphenism is important for our understanding of what this signaling is used for.

microbiology↗

bioRxiv2024

Chromosome-level genome assembly and annotation of the social amoeba Dictyostelium firmibasis

Dicytostelium firmibasis is a member of Dictyostelia, a group of social amoebae that upon starvation display aggregative multicellularity where the amoebae transition from uni-to multicellular life. The D. firmibasis genome assembly that is currently available is of limited use due to its low contiguity, large number of undetermined bases, and lack of annotations. Here we used Nanopore long read sequencing, complemented with Illumina sequencing, and developmental transcriptomics as well as small RNA-sequencing, to present a new, fully annotated, chromosome-level D. firmibasis genome assembly. The new assembly contains no undetermined bases, and consists mainly of six large contigs representing the chromosomes, as well as a complete mitochondrial genome. This new genome assembly will be a valuable tool, allowing comprehensive comparison to Dictyostelium discoideum, the dictyostelid genetically tractable model. Further, the new genome will be important for studies of evolutionary processes governing the transition from unicellular to multicellular organisms and will aid in the sequencing and annotation of other dictyostelids genomes, many of which are currently of poor quality.

genomics↗

bioRxiv2019

Class II contact-dependent growth inhibition (CDI) systems allow for broad-range cross-species toxin delivery

Contact-dependent growth inhibition (CDI) allows bacteria to recognize kin cells in mixed bacterial populations. In Escherichia coli, CDI mediated effector delivery has been shown to be species-specific, with a preference for the own strain over others. This specificity is achieved through an interaction between a receptor-binding domain in the CdiA protein and its cognate receptor protein on the target cell. But how conserved this specificity is has not previously been investigated in detail. Here we show that three different class II CdiA receptor-binding domains and their Enterobacter cloacae analog are highly promiscuous, allowing for efficient effector delivery into several different Enterobacteriaceae species, including Escherichia, Enterobacter, Klebsiella and Salmonella spp. In addition, although we observe a preference for some receptors over others, this did not limit cross-species effector delivery, suggesting that class II CdiA proteins can allow for broad-range and cross-species growth inhibition in mixed bacterial populations.

evolutionary biology↗