Biology subjects

Guler, P.

Publications and source records attributed to Guler, P..

5 recordsLinked to original sources

bioRxiv2026

Highly specific mRNA cleavage by the MazF endoribonuclease orchestrates stationary transcriptome remodeling and rapid regrowth in Gram-positive bacteria

Bacterial toxin-antitoxin (TA) systems are classically viewed as stress-activated toxic switches. Specifically, ribonucleolytic toxins are thought to indiscriminately cleave RNA to halt cellular growth. We recently showed that the MazF toxin of Bacillus subtilis targets an unusually strict 6bp RNA cleavage sequence, but the implications of this stringent specificity were unknown. Here, we demonstrate that the MazEF system functions as a non-lethal post-transcriptional regulator in B. subtilis. Using a specialized single cell fluorescent reporter and transcriptome profiling, we show that MazF is uniformly activated across the population upon entry into the stationary phase, where it cleaves a narrow mRNA regulon to reshape gene expression. Rather than inhibiting growth, MazF activation tunes down the Spo0A stress response by repressing the mRNA level of its kinases. Reduced stress leads to an adaptive shortening of the lag phase upon nutrient replenishment. Furthermore, MazEFs structural architecture, cleavage specificity, and impact on growth recovery are highly conserved across Gram-positive bacteria. Altogether, our findings redefine a paradigmatic toxin as a precision global mRNA stress regulator that primes cells for rapid regrowth. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/743204v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1790c77org.highwire.dtl.DTLVardef@215962org.highwire.dtl.DTLVardef@1734aa4org.highwire.dtl.DTLVardef@296b45_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Arbitrium systems control lysis/lysogeny through the regulation of small antirepressor proteins

Many temperate Bacillus phages utilize the arbitrium signaling system to control lysis/lysogeny decisions. While the function of the arbitrium signal AimP and its receptor AimR are well known, it is unclear how they control lysis in most arbitrium systems. Here, we show that a large majority of arbitrium systems are embedded in an extended module with three additional components; A small antirepressor protein (AimX), the phage repressor (AimC) and an adjacent cro-like protein (AimL). AimR-dependent activation of AimX is necessary for lysis both during infection and lytic induction. Molecular analysis suggests that AimX directly binds AimC and prevents its oligomerization and binding to its regulated aimL promoter. Our work therefore uncovers the main mechanism by which arbitrium systems regulate lysis and point to the central role of small proteins in phage decision making. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/689978v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@63dd49org.highwire.dtl.DTLVardef@54e7ecorg.highwire.dtl.DTLVardef@466235org.highwire.dtl.DTLVardef@d98ef2_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

High defense system expression broadens protection range at the cost of increased autoimmunity

The evolutionary arms race between bacteria and their phage viruses has given rise to elaborate anti-phage defense mechanisms. Major advances have been made in revealing the molecular details underlying diverse defense systems, but general principles and constraints are largely unkown. Defense systems are often tested against a diverse set of phages, revealing widely varying protection ranges. While these disparities are usually attributed to differences in mechanism, here we show that increasing expression of defense systems can greatly enhance their protection range. This holds true for disparate mechanisms, and is achieved by circumventing phage strategies for overcoming bacterial defense. However, increased defense system expression comes with a heavy cost of autoimmunity. Therefore, the expression level of defense systems controls a tradeoff between protection range on the one hand and autoimmunity on the other. We discuss how this tradeoff may drive the regulation of defense systems expression and the acquisition of multiple systems within the same genome.

microbiology↗

bioRxiv2023

Arbitrium communication controls phage life-cycle through modulation of a bacterial anti-phage defense system

Bacterial temperate viruses (phages) have to decide between a quiescent (lysogenic) and virulent (lytic) lifestyle in the face of a variety of phage defense systems. Multiple Bacilli phage families have been shown to use the arbitrium communication system, but the mechanism by which the arbitrium system exerts its function remains largely unknown. Here we study phage {phi}3T, in which arbitrium was originally identified, and find that arbitrium communication controls the phage life-cycle through interactions with a host-encoded defense system. Under lytic conditions, the arbitrium system expresses an anti-toxin, AimX, which blocks the RNA ribonuclease activity of MazF, part of the MazEF toxin-antitoxin system. When arbitrium signal concentration is high, AimX is not expressed and MazF remains active. We find that this activity is necessary for lysogenization. Finally, we show that MazEF acts as a defense system, and protects bacteria against a lytic {phi}3T mutant which lacks AimX and an additional later-expressed MazE-like antitoxin, YosL. Altogether, our results show how a bacterial defense system has been co-opted by phages to control their lysis/lysogeny decision-making.

microbiology↗

bioRxiv2021

Dormant phages communicate to control exit from lysogeny

Temperate bacterial viruses (phages) can transition between lysis - replicating and killing the host, and lysogeny - existing as dormant prophages while keeping the host viable. It was recently shown that upon invading a naive cell, some phages communicate using a peptide signal, termed arbitrium, to control the decision of entering lysogeny. Whether communication can also serve to regulate exit from lysogeny (known as phage induction) remains unclear. Here we show that arbitrium-coding prophages continue to communicate from the lysogenic state by secreting and sensing the arbitrium signal. Signaling represses DNA-damage dependent phage induction, enabling prophages to reduce induction rate when surrounded by other lysogens. We show that the mechanism by which DNA damage and communication are integrated differs between distantly related arbitrium-coding phages. Additionally, signaling by prophages tilts the decision of nearby infecting phages towards lysogeny. Altogether, we find that phages use small molecule communication throughout their entire life-cycle to measure the abundance of lysogens in the population, thus avoiding wasteful attempts at secondary infections when they are unlikely to succeed.

microbiology↗