A Newly Identified Prophage Gene, ymfM , Causes SOS-Inducible Filamentation in Escherichia coli

Abstract

Rod-shaped bacteria such as Escherichia coli can regulate cell division in response to stress, leading to filamentation, a process where cell growth and DNA replication continues in the absence of division, resulting in elongated cells. The classic example of stress is DNA damage which results in the activation of the SOS response. While the inhibition of cell division during SOS has traditionally been attributed to SulA in E. coli, a previous report suggests that the e14 prophage may also encode an SOS-inducible cell division inhibitor, previously named SfiC. However, the exact gene responsible for this division inhibition has remained unknown for over 35 years. A recent high-throughput over-expression screen in E. coli identified the e14 prophage gene, ymfM, as a potential cell division inhibitor. In this study, we show that the inducible expression of ymfM from a plasmid causes filamentation. We show that this expression of ymfM results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in E. coli, SulA, SlmA and MinC. We confirm that ymfM is the gene responsible for the SfiC phenotype as it contributes to the filamentation observed during the SOS response. This function is independent of SulA, highlighting that multiple alternative division inhibition pathways exist during the SOS response. Our data also highlight that our current understanding of cell division regulation during the SOS response is incomplete and raises many questions regarding how many inhibitors there actually are and their purpose for the survival of the organism. Importance: Filamentation is an important biological mechanism which aids in the survival, pathogenesis and antibiotic resistance of bacteria within different environments, including pathogenic bacteria such as uropathogenic Escherichia coli. Here we have identified a bacteriophage-encoded cell division inhibitor which contributes to the filamentation that occurs during the SOS response. Our work highlights that there are multiple pathways that inhibit cell division during stress. Identifying and characterising these pathways is a critical step in understanding survival tactics of bacteria which become important when combating the development of bacterial resistance to antibiotics and their pathogenicity.

Genomic and Phenotypic Analysis of Heat and Sanitizer Resistance in Escherichia coli from Beef in Relation to the Locus of Heat Resistance

“…The findings on similar MIC values of various groups E. coli in the present study were consistent with the lack of difference in the efflux pump related genes in the respective groups. A number of genes on cryptic prophages in E. coli have been reported to be involved in stress response including resistance to antibiotics such as novobiocin (37)(38)(39). None of these genes were overrepresented in LHR-positive isolates, despite the overrepresentation of cryptic prophage genes in general in this group.. Sublethal heat shock at 42C unfolds or misfolds cellular proteins, resulting in protein aggregates if these proteins are not refolded or degraded (40,41).…”

Growth‐dependent heterogeneity in the DNA damage response in Escherichia coli

“…Classically, during balanced growth, the population doubling rate (µ) is directly related to the exponential rate of mass accumulation (λ = ln2*µ) (Monod, 1949). When cells induce the SOS response, they become filamentous because they continue adding mass whilst delaying division as a result of the induction of SulA, YmfM and potentially other division inhibitors (Ansari et al , 2021). Heterogeneity in the level of SOS induction produces strong heterogeneity in the division rates of individual cells in the population.…”

Molecular Signatures of the Eagle Effect Induced by the Artificial Siderophore Conjugate LP-600 in E. coli

“…However, a few were found to have an association with inhibition of cell division and filamentation. 44,45 Ansari et al showed that overexpression of the SOS-induced ymf M gene caused filamentation and inhibition of Z ring formation, thereby halting cell division. 45 Filamentation helps E. coli to survive in different environments and contributes to antibiotic resistance.…”