Biology subjects

Eldar, A.

Publications and source records attributed to Eldar, A..

8 recordsLinked to original sources

bioRxiv2026

A phage communication peptide alters Bacillus subtilis colony development and promotes sporulation

Temperate Bacillus phages use arbitrium peptides to coordinate lysis-lysogeny decisions, but whether the mature communication peptide can be sensed directly by Bacillus subtilis and affect its physiology and behavior is unknown. Here we show that the {varphi}3T arbitrium peptide SAIRGA elicits a sequence- and stereochemistry-dependent response in Bacillus subtilis that is strongly expressed in surface-grown colony biofilms but is not accompanied by comparable changes in planktonic growth or static-liquid pellicle morphology. The response persists in the absence of AimR, the canonical arbitrium receptor. Within colonies, SAIRGA alters spatial PtapA activity and increases heat-resistant spore formation without increasing total viable cell yield. Untargeted metabolomics reveals broad dose-dependent remodeling that tracks peptide activity, while program-level proteomics independently converges on late-sporulation and mature-spore-associated states. This study highlights how a phage-derived peptide may act as a signal, enabling the host to pivot toward a survival-focused developmental state.

microbiology↗

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

An unprecedented DNA recognition-mimicry switch governs induction in arbitrium phages

Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPBeta-like phages use arbitrium signalling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPBeta-like phage repressor, binds DNA via a novel mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of a newly identified antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognised by the repressor, inactivating its function and inducing phage. This mechanism is conserved across SP{beta}-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for induction when arbitrium levels are high. Our results uncover the mechanism underlying the double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighbouring prophages.

molecular biology↗

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

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↗

bioRxiv2020

A mobile genetic element increases bacterial host fitness by manipulating development

Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes: biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.

microbiology↗

bioRxiv2019

Intercellular positive-feedback loops promote the evolutionary stability of microbial cooperative behaviors

Microbial cooperation enables groups of conspecific cells to perform tasks that cannot be performed efficiently by individual cells, such as utilization of various secreted public-good molecules, communication via quorum-sensing, or the formation of multicellular structures. Cooperation is often costly and therefore susceptible to exploitation by cheater cells, which enjoy the benefit of cooperation without investing in it. While population structure is key to the maintenance of cooperation, it remains unclear whether other mechanisms help in stabilizing microbial cooperation. Like other microbial traits, cooperation is often governed by complex regulatory networks, and one reoccurring motif is an intercellular positive-feedback loop, where a secreted molecule, e.g. a public-good or a quorum-sensing signaling molecule, activates its own production in all surrounding cells. Here we investigate the role of intercellular feedbacks in the maintenance of bacterial cooperation. We combine theory with a synthetic-biology approach, using swarming motility of Bacillus subtilis engineered variants, to compare the response of open-loop and feedback cooperators to the presence of cheaters. We find that positive feedbacks on cooperative behaviors - either directly or through a feedback on quorum-sensing - maintain cooperation in a broader range of environments, relieving the requirement for a strong population structure. Our results directly demonstrate the stabilizing effect of intercellular positive feedbacks on cooperative behaviors, and suggests an explanation for their abundance in regulatory networks of bacterial cooperation.

systems biology↗