Ansari Shirin, Walsh James C, Bottomley Amy L, Duggin Iain G, Burke Catherine, Harry Elizabeth J
The ithree institute, Faculty of Science, University of Technology Sydney, Sydney, Australia.
EMBL Australia Node in Single Molecule Science and ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, University of New South Wales, Sydney, Australia.
J Bacteriol. 2021 Jun 1;203(11). doi: 10.1128/JB.00646-20. Epub 2021 Mar 15.
Rod-shaped bacteria such as 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 , 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 identified the e14 prophage gene, , as a potential cell division inhibitor. In this study, we show that the inducible expression of from a plasmid causes filamentation. We show that this expression of results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in , SulA, SlmA and MinC. We confirm that 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.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 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.
诸如大肠杆菌这样的杆状细菌能够响应应激来调节细胞分裂，从而导致丝状化，即细胞在不进行分裂的情况下持续生长和DNA复制，最终产生细长细胞的过程。应激的经典例子是DNA损伤，它会导致SOS反应的激活。虽然传统上认为在大肠杆菌中SOS反应期间细胞分裂的抑制归因于SulA，但之前的一份报告表明，e14原噬菌体可能也编码一种SOS诱导型细胞分裂抑制剂，之前被命名为SfiC。然而，在超过35年的时间里，负责这种分裂抑制的确切基因一直未知。最近在大肠杆菌中进行的一项高通量过表达筛选确定了e14原噬菌体基因sfiA是一种潜在的细胞分裂抑制剂。在本研究中，我们表明从质粒诱导表达sfiA会导致丝状化。我们表明sfiA的这种表达会导致Z环形成的抑制，并且独立于大肠杆菌中已被充分表征的FtsZ环组装抑制剂SulA、SlmA和MinC。我们证实sfiA是导致SfiC表型的基因，因为它促成了在SOS反应期间观察到的丝状化。该功能独立于SulA，这突出表明在SOS反应期间存在多种替代的分裂抑制途径。我们的数据还突出表明，我们目前对SOS反应期间细胞分裂调控的理解是不完整的，并引发了许多问题，例如实际上有多少种抑制剂以及它们对生物体生存的作用。丝状化是一种重要的生物学机制，有助于细菌在不同环境中的生存、致病和抗生素抗性，包括诸如尿路致病性大肠杆菌这样的病原菌。在这里，我们鉴定出一种噬菌体编码的细胞分裂抑制剂，它促成了SOS反应期间发生的丝状化。我们的工作突出表明，在应激期间存在多种抑制细胞分裂的途径。识别和表征这些途径是理解细菌生存策略的关键一步，而这在对抗细菌对抗生素的抗性及其致病性发展时变得至关重要。
