scholarly journals Physiology of guanosine-based second messenger signaling in Bacillus subtilis

2020 ◽  
Vol 401 (12) ◽  
pp. 1307-1322
Author(s):  
Gert Bange ◽  
Patricia Bedrunka
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Second Messengers ◽  
Model Organism ◽  
Physiological Regulation ◽  
Open Questions ◽  
Key Players ◽  
Stress Signals ◽  
Second Messenger Signaling ◽  
Synthesis And Degradation

AbstractThe guanosine-based second messengers (p)ppGpp and c-di-GMP are key players of the physiological regulation of the Gram-positive model organism Bacillus subtilis. Their regulatory spectrum ranges from key metabolic processes over motility to biofilm formation. Here we review our mechanistic knowledge on their synthesis and degradation in response to environmental and stress signals as well as what is known on their cellular effectors and targets. Moreover, we discuss open questions and our gaps in knowledge on these two important second messengers.

scholarly journals Thio Derivatives of 2(5H)-Furanone As Inhibitors against Bacillus subtilis Biofilms

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 102-107 ◽  
Author(s):  
E. Yu. Trizna ◽  
E. N. Khakimullina ◽  
L. Z. Latypova ◽  
A. R. Kurbangalieva ◽  
I. S. Sharafutdinov ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Wide Spectrum ◽  
Model Organism ◽  
Human Immune System ◽  
Gram Positive ◽  
Bacterium Bacillus Subtilis ◽  
Bacterial Sensitivity ◽  
Bacterium Bacillus ◽  
Derivatives Of

Gram-positive bacteria cause a wide spectrum of infectious diseases, including nosocomial infections. While in the biofilm, bacteria exhibit increased resistance to antibiotics and the human immune system, causing difficulties in treatment. Thus, the development of biofilm formation inhibitors is a great challenge in pharmacology. The gram-positive bacterium Bacillus subtilis is widely used as a model organism for studying biofilm formation. Here, we report on the effect of new synthesized 2(5Н)-furanones on the biofilm formation by B.subtilis cells. Among 57 compounds tested, sulfur-containing derivatives of 2(5H)-furanone (F12, F15, and F94) repressed biofilm formation at a concentration of 10 g/ml. Derivatives F12 and F94 were found to inhibit the biosynthesis of GFP from the promoter of the eps operon encoding genes of the biofilm exopolysaccharide synthesis (EPS). Using the differential fluorescence staining of alive/dead cells, we demonstrated an increased bacterial sensitivity to antibiotics (kanamycin and chloramphenicol) in the presence of F12, F15, and F94, with F12 being the most efficient one. The derivative F15 was capable of disrupting an already formed biofilm and thereby increasing the efficiency of antibiotics.

scholarly journals An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis

2015 ◽  
Vol 197 (20) ◽  
pp. 3265-3274 ◽  
Author(s):  
Jan Gundlach ◽  
Felix M. P. Mehne ◽  
Christina Herzberg ◽  
Jan Kampf ◽  
Oliver Valerius ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacillus Subtilis ◽  
Nitrogen Source ◽  
Second Messengers ◽  
Regulatory Protein ◽  
Control Cell ◽  
Model Organism ◽  
Second Messenger ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACTGram-positive bacteria synthesize the second messenger cyclic di-AMP (c-di-AMP) to control cell wall and potassium homeostasis and to secure the integrity of their DNA. In the firmicutes, c-di-AMP is essential for growth. The model organismBacillus subtilisencodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-AMP, respectively. Among the three cyclases, CdaA is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di-AMP that is required for cell wall homeostasis. Here, we demonstrate that CdaA localizes to the membrane and forms a complex with the regulatory protein CdaR and the glucosamine-6-phosphate mutase GlmM. Interestingly,cdaA,cdaR, andglmMform a gene cluster that is conserved throughout the firmicutes. This conserved arrangement and the observed interaction between the three proteins suggest a functional relationship. Our data suggest that GlmM and GlmS are involved in the control of c-di-AMP synthesis. These enzymes convert glutamine and fructose-6-phosphate to glutamate and glucosamine-1-phosphate. c-di-AMP synthesis is enhanced if the cells are grown in the presence of glutamate compared to that in glutamine-grown cells. Thus, the quality of the nitrogen source is an important signal for c-di-AMP production. In the analysis of c-di-AMP-degrading phosphodiesterases, we observed that both phosphodiesterases, GdpP and PgpH (previously known as YqfF), contribute to the degradation of the second messenger. Accumulation of c-di-AMP in agdpP pgpHdouble mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA.IMPORTANCEBacteria use second messengers for signal transduction. Cyclic di-AMP (c-di-AMP) is the only second messenger known so far that is essential for a large group of bacteria. We have studied the regulation of c-di-AMP synthesis and the role of the phosphodiesterases that degrade this second messenger. c-di-AMP synthesis strongly depends on the nitrogen source: glutamate-grown cells produce more c-di-AMP than glutamine-grown cells. The accumulation of c-di-AMP in a strain lacking both phosphodiesterases is toxic and results in inactivation of the diadenylate cyclase CdaA. Our results suggest that CdaA is the critical diadenylate cyclase that produces the c-di-AMP that is both essential and toxic upon accumulation.

scholarly journals Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation

2016 ◽  
Vol 7 ◽  
Author(s):  
Jan Gundlach ◽  
Hermann Rath ◽  
Christina Herzberg ◽  
Ulrike Mäder ◽  
Jörg Stülke
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Second Messenger ◽  
Second Messenger Signaling

scholarly journals Intracellular localization of the mycobacterial stressosome complex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malavika Ramesh ◽  
Ram Gopal Nitharwal ◽  
Phani Rama Krishna Behra ◽  
B. M. Fredrik Pettersson ◽  
Santanu Dasgupta ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Fluorescence Microscopy ◽  
Bacillus Cereus ◽  
Intracellular Localization ◽  
Sigma Factors ◽  
Alternative Sigma Factors ◽  
Expression Of Genes ◽  
Molecular Machinery ◽  
Stress Signals ◽  
Activation Pathways

AbstractMicroorganisms survive stresses by alternating the expression of genes suitable for surviving the immediate and present danger and eventually adapt to new conditions. Many bacteria have evolved a multiprotein "molecular machinery" designated the "Stressosome" that integrates different stress signals and activates alternative sigma factors for appropriate downstream responses. We and others have identified orthologs of some of the Bacillus subtilis stressosome components, RsbR, RsbS, RsbT and RsbUVW in several mycobacteria and we have previously reported mutual interactions among the stressosome components RsbR, RsbS, RsbT and RsbUVW from Mycobacterium marinum. Here we provide evidence that "STAS" domains of both RsbR and RsbS are important for establishing the interaction and thus critical for stressosome assembly. Fluorescence microscopy further suggested co-localization of RsbR and RsbS in multiprotein complexes visible as co-localized fluorescent foci distributed at scattered locations in the M. marinum cytoplasm; the number, intensity and distribution of such foci changed in cells under stressed conditions. Finally, we provide bioinformatics data that 17 (of 244) mycobacteria, which lack the RsbRST genes, carry homologs of Bacillus cereus genes rsbK and rsbM indicating the existence of alternative σF activation pathways among mycobacteria.

scholarly journals An RNA-centric view on gut Bacteroidetes

2020 ◽  
Vol 402 (1) ◽  
pp. 55-72
Author(s):  
Daniel Ryan ◽  
Gianluca Prezza ◽  
Alexander J. Westermann
Keyword(s):  
Noncoding Rna ◽  
Case Reports ◽  
Model Organism ◽  
Global Gene Expression ◽  
Host Cells ◽  
Human Gut ◽  
Open Questions ◽  
Obligate Anaerobic ◽  
Bacterial Rna ◽  
Rna Biology

AbstractBacteria employ noncoding RNAs to maintain cellular physiology, adapt global gene expression to fluctuating environments, sense nutrients, coordinate their interaction with companion microbes and host cells, and protect themselves against bacteriophages. While bacterial RNA research has made fundamental contributions to biomedicine and biotechnology, the bulk of our knowledge of RNA biology stems from the study of a handful of aerobic model species. In comparison, RNA research is lagging in many medically relevant obligate anaerobic species, in particular the numerous commensal bacteria comprising our gut microbiota. This review presents a guide to RNA-based regulatory mechanisms in the phylum Bacteroidetes, focusing on the most abundant bacterial genus in the human gut, Bacteroides spp. This includes recent case reports on riboswitches, an mRNA leader, cis- and trans-encoded small RNAs (sRNAs) in Bacteroides spp., and a survey of CRISPR-Cas systems across Bacteroidetes. Recent work from our laboratory now suggests the existence of hundreds of noncoding RNA candidates in Bacteroides thetaiotaomicron, the emerging model organism for functional microbiota research. Based on these collective observations, we predict mechanistic and functional commonalities and differences between Bacteroides sRNAs and those of other model bacteria, and outline open questions and tools needed to boost Bacteroidetes RNA research.

scholarly journals Deletion of Rap‐Phr systems in Bacillus subtilis influences in vitro biofilm formation and plant root colonization

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Mathilde Nordgaard ◽  
Rasmus Møller Rosenbek Mortensen ◽  
Nikolaj Kaae Kirk ◽  
Ramses Gallegos‐Monterrosa ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Root Colonization ◽  
Plant Root

scholarly journals Bicarbonate Evokes Reciprocal Changes in Intracellular Cyclic di-GMP and Cyclic AMP Levels in Pseudomonas aeruginosa

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 519
Author(s):  
Kasidid Ruksakiet ◽  
Balázs Stercz ◽  
Gergő Tóth ◽  
Pongsiri Jaikumpun ◽  
Ilona Gróf ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Biofilm Formation ◽  
Second Messengers ◽  
Brain Heart Infusion ◽  
Ambient Air ◽  
Dependent Manner ◽  
Environmental Signals ◽  
Common Causes ◽  
Camp Levels

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO3 in 5% CO2 (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO3− exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO3−. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO3− per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.

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