Biology subjects

Samir, S.

Publications and source records attributed to Samir, S..

6 recordsLinked to original sources

bioRxiv2026

Regulation of cyanobacterial type IV pilus-dependent functions by interaction between a c-di-GMP receptor and two transcription factors

Cyanobacteria utilize type IV pili for many behavioural responses, such as phototaxis, aggregation, floating, and DNA uptake. Type IV pilus-dependent functions are regulated by the nucleotide second messengers, c-di-GMP and cAMP. In this study, we investigated the role of a recently identified c-di-GMP receptor (CdgR) in cyanobacteria that harbours a ComFB domain. ComFB-domain proteins are widespread in cyanobacteria and are also present in heterotrophic bacteria. We demonstrated that the CdgR homolog from the cyanobacterium Synechocystis sp. PCC 6803, a model organism for studying type IV pilus-dependent functions, specifically binds to c-di-GMP. Genetic and phenotypic analyses revealed that Synechocystis CdgR is involved in phototactic motility and natural competence. Inactivation of cdgR resulted in altered expression of specific sets of minor pilins, which are essential for motility or natural competence. We identified interactions between CdgR and the CRP-family transcription factors, SyCRP1 and SyCRP2. Disruption of these CdgR-SyCRP1 and CdgR/SyCRP2 complexes is initiated by elevated c-di-GMP levels. Moreover, the assembly and stability of these complexes are influenced by other cyclic nucleotides, such as cAMP and c-di-AMP. These observed interactions imply a complex regulatory mechanism by which CdgR influences gene expression in response to cyclic nucleotide messenger signalling, particularly c-di-GMP. The present findings highlight the importance of CdgR in c-di-GMP signalling and its role in regulating type IV pilus-dependent functions in Synechocystis. The modulation of the expression of specific minor pilin genes by CdgR, through interactions with the transcription factors SyCRP1 and SyCRP2, contributes to the establishment of multiple type IV pilus functions and adaptive behaviours of cyanobacteria.

microbiology↗

bioRxiv2025

c-di-GMP-Dependent Regulation of Motility by comFB and comFC

ComFB is encoded in the comF operon of Bacillus subtilis, situated between the genes for ComFA and ComFC. The latter two proteins are essential for natural transformation, whereas ComFB is dispensable. We show here that ComFB binds specifically and with high affinity to the second messenger c-di-GMP and that ComFB acts as a c-di-GMP receptor to inhibit swarming and swimming motility, apparently by interfering with flagellar activity. We show further that in the absence of ComFC, swarming is completely abrogated by a mechanism that requires FB. These results reveal a new c-di-GMP regulatory system that controls motility independently of MotI. IMPORTANCEBacterial motility is subject to tight regulation, and the second messenger c-di-GMP is often involved in the production and activity of flagella. Revealing the mechanisms of these regulatory pathways is broadly important for understanding bacterial motility and of c-di-GMP-related processes. We show that ComFB is a specific, high-affinity receptor for c-di-GMP that decreases the activity of flagella to control swarming and swimming motility in Bacillus subtilis.

microbiology↗

bioRxiv2024

ComFB, a new widespread family of c-di-NMP receptor proteins

Cyclic dimeric GMP (c-di-GMP) is a widespread bacterial second messenger that controls a variety of cellular functions, including protein and polysaccharide secretion, motility, cell division, cell development, and biofilm formation, and contributes to the virulence of some important bacterial pathogens. While the genes for diguanylate cyclases and c-di-GMP hydrolases (active or mutated) can be easily identified in microbial genomes, the list of c-di-GMP receptor domains is quite limited, and only two of them, PliZ and MshEN, are found across multiple bacterial phyla. Recently, a new c-di-GMP receptor protein, named CdgR or ComFB, has been identified in cyanobacteria and shown to regulate their cell size and, more recently, natural competence. Sequence and structural analysis indicated that CdgR is part of a widespread ComFB protein family, named after the "late competence development protein ComFB" from Bacillus subtilis. This prompted the suggestion that ComFB and ComFB-like proteins could also be c-di-GMP receptors. Indeed, we revealed that ComFB proteins from Gram-positive B. subtilis and Thermoanaerobacter brockii were able to bind c-di-GMP with high-affinity. The ability to bind c-di-GMP was also demonstrated for the ComFB proteins from clinically relevant Gram-negative bacteria Vibrio cholerae and Treponema denticola. These observations indicate that the ComFB family serves as yet another widespread family of bacterial c-di-GMP receptors. Incidentally, some ComFB proteins were also capable of c-di-AMP binding, identifying them as a unique family of c-di-NMP receptor proteins. The overexpression of comFB in B. subtilis, combined with an elevated concentration of c-di-GMP, suppressed motility, attesting to the biological relevance of ComFB as a c-di-GMP binding protein. IMPORTANCEThe cellular content of the bacterial second messenger c-di-GMP is controlled by c-di-GMP synthases (GGDEF domains) and hydrolases (EAL or HD-GYP domains), whose activities, in turn, respond to the signals perceived by their upstream sensory domains. Cyclic-di-GMP transmits the signals to a variety of its targets, which may contain inactivated GGDEF, EAL, or HD-GYP domains, widespread PilZ or MshEN domains, or various lineage-specific c-di-GMP receptors. Many organisms encode multiple GGDEF domains but few c-di-GMP-binding proteins, suggesting the existence of still unidentified c-di-GMP receptors. Here, we demonstrate that the ComFB family proteins, which include the recently characterized cyanobacterial CdgR/ComFB, constitute yet another widespread family of bacterial c-di-NMP receptors. We additionally show that ComFB controls bacillar motility in a c-di-GMP-dependent manner.

microbiology↗

bioRxiv2023

The second messenger c-di-AMP controls natural competence via ComFB signaling protein

Natural competence requires a contractile pilus system. Here, we provide evidence that the pilus biogenesis and natural competence in cyanobacteria are regulated by the second messenger c-di-AMP. Furthermore, we show that the ComFB signaling protein is a novel c-di-AMP-receptor protein, widespread in bacterial phyla, and required for pilus biogenesis and DNA uptake.

microbiology↗

bioRxiv2023

Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1

Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in ex vivo assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.

microbiology↗

bioRxiv2020

Whole genome analysis of four Bangladeshi individuals

Whole-genome sequencing (WGS) is a comprehensive method for analysing entire genomes and this has been instrumental in characterizing the single nucleotide polymorphisms associated with different diseases including cancer, diabetes, cardiovascular diseases and many others. In this paper we undertake a pilot study for sequencing four Bangladeshi individuals and profiling their single nucleotide variants. Our findings shed possible light on specific biological pathways effected by such variants in this population.

genomics↗