Article
Infectious Diseases
Dmitrijs Lubriks, Klara Haldimann, Sven N. Hobbie, Andrea Vasella, Edgars Suna, David Crich
Summary: The synthesis, antiribosomal, and antibacterial activity of two anomers of a novel apralog, 5-O-(5-amino-3-C-dimethylaminopropyl-D-ribofuranosyl)apramycin, were studied. Both anomers showed strong activity against bacterial ribosomes, MRSA, and various wild-type Gram-negative pathogens. These compounds were also found to be effective against aminoglycoside modifying enzymes, enabling them to retain their activity in the presence of these enzymes. Surprisingly, the two anomers exhibited comparable activity against bacterial ribosomes and the tested bacterial strains.
Article
Biochemistry & Molecular Biology
Justin E. Clarke, Kiran Sabharwal, Louise Kime, Kenneth J. McDowall
Summary: RNase E is an endoribonuclease that plays a crucial role in the maturation of RNA involved in translation and mRNA degradation. It binds to structured RNA elements, activating catalysis and facilitating tRNA processing and potential mRNA degradation. The recognition of structured elements is mediated by a newly discovered groove, essential for E. coli cell viability and distinct from the RNase G family.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Monica P. Hui, Joel G. Belasco
Summary: A key pathway for mRNA degradation in bacterial cells involves the conversion of initial 5'-terminal triphosphate to monophosphate, rendering transcripts vulnerable to ribonucleases. Cytidylate kinase has been identified as another protein affecting mRNA degradation in E. coli by influencing the phosphorylation state of RNA and nucleotide incorporation during transcription. These findings suggest dual signaling pathways by which nucleotide metabolism can impact mRNA degradation in bacteria.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Infectious Diseases
Lachlan Jake Munro, Douglas B. Kell
Summary: Antibiotic resistance is a major global healthcare issue, and modification of membrane transporters is a key mechanism driving this resistance. This study demonstrates that transporters play a role in modulating the efficacy of almost all antimicrobial compounds tested, potentially influencing the development of antimicrobial resistance.
Article
Biochemistry & Molecular Biology
Arancha Catalan-Moreno, Marta Cela, Pilar Menendez-Gil, Naiara Irurzun, Carlos J. Caballero, Isabelle Caldelari, Alejandro Toledo-Arana
Summary: The production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches, which adopt alternative RNA structures at different temperatures, affecting the translation process. Simultaneous deletion of these genes or their RNA thermoswitches significantly decreases the growth rate of the bacteria at lower temperatures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Calum M. Webster, Ayrianna M. Woody, Safura Fusseini, Louis G. Holmes, Gary K. Robinson, Mark Shepherd
Summary: Loss of aerobic respiration in Gram-negative bacteria diminishes the efficacy of bactericidal antibiotics. Reactive oxygen species (ROS) and the proton motive force (PMF) have been shown to play a role in antibiotic toxicity. This study demonstrates that maintenance of PMF, rather than induction of ROS production, is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycoside antibiotics.
ARCHIVES OF MICROBIOLOGY
(2022)
Article
Chemistry, Organic
Jian Li, Hans Renata
Summary: A novel chemoenzymatic approach was developed for the synthesis of fasamycin A, a halogenated naphthacenoid with activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. The synthesis involved combining two fragments through a Sammes annulation to form a dimethylnaphthacenone system, followed by enzymatic halogenation to introduce the necessary chlorine substituent at a later stage.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Souvik Bhattacharyya, Madhumita Bhattacharyya, Dylan M. Pfannenstiel, Anjan K. Nandi, YuneSahng Hwang, Khang Ho, Rasika M. Harshey
Summary: Efflux is not only a mechanism for bacteria to acquire antibiotic resistance, but also promotes the accumulation of antibiotic resistance mutations (ARMs). The study shows that high efflux leads to downregulation of specific DNA repair pathways, resulting in an increase in ARMs. Additionally, bacteria populations with high efflux serve as reservoirs of ARMs, even in the absence of antibiotic selection pressure. This finding is particularly significant for the treatment of antibiotic-resistant biofilms.
Article
Biochemistry & Molecular Biology
Jamie Richards, Joel G. Belasco
Summary: In many bacteria, RNase E controls the lifespan of most mRNAs by degrading RNAs with a 5' monophosphate and cleaving them linearly from the 5' terminus. Obstacles encountered along the scanning path of this enzyme, such as bound proteins or ribosomes or base pairing, determine its rate of cleavage at distal sites. We found that the protection provided by these obstacles depends on the size and persistence of the structural discontinuities they create, rather than their molecular composition. Incrementally larger discontinuities have a proportionally greater impact on mRNA stability, suggesting that the effect of obstacles on scanning is not binary.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Daniel P. Cetnar, Howard M. Salis
Summary: mRNA degradation is a complex process that affects gene expression levels. Through a synthetic biology approach, this study identified factors affecting mRNA stability in bacterial operons, such as the impact of long single-stranded RNA in 5' UTR and translation rates on mRNA levels. The research also developed biophysical models and design rules to control mRNA stability, facilitating the automated design of engineered genetic systems with specific functionalities.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ioly Kotta-Loizou, Maria Grazia Giuliano, Milija Jovanovic, Jorrit Schaefer, Fuzhou Ye, Nan Zhang, Danai Athina Irakleidi, Xiaojiao Liu, Xiaodong Zhang, Martin Buck, Christoph Engl
Summary: RtcR CARF domain controls expression of two RNA repair enzymes, and RtcAB play a crucial role in RtcR-dependent transcription activation. Additionally, tmRNA repaired by RtcB may serve as a novel RNA repair-dependent activating signal.
Article
Multidisciplinary Sciences
Mikhail Metelev, Erik Lundin, Ivan L. Volkov, Arvid H. Gynna, Johan Elf, Magnus Johansson
Summary: Metelev et al. used single-molecule tracking to study translation kinetics in E. coli cells and found that over 90% of ribosomes are engaged in translation at any given time. They also discovered that translation of poly-cistronic mRNAs is predominantly initiated by 70S re-initiation instead of 30S re-initiation. Additionally, they observed significant binding of ribosomes with altered anti-Shine-Dalgarno sequences to endogenous mRNAs.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Haixiu Wang, Eric Cox, Bert Devriendt
Summary: Enterotoxigenic Escherichia coli (ETEC) strains recognize and respond to factors secreted by gut epithelial cells, leading to transcriptional modulation of key ETEC virulence genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Katia Ospino, Beny Spira
Summary: This study investigated the effects of glyphosate on the resistance, tolerance, or persistence of bacteria towards antibiotics, as well as the role of (p)ppGpp in this process. The results showed that glyphosate did not affect the minimum inhibitory concentration of tested antibiotics, but it enhanced bacterial tolerance and/or persistence towards them. The increase in ciprofloxacin and kanamycin tolerance was partially dependent on the presence of relA, while the strong increase in ampicillin tolerance caused by glyphosate was independent of relA. The study concluded that glyphosate contributes to the temporary increase in E. coli tolerance or persistence by inducing aromatic amino acid starvation, but does not affect antibiotic resistance.
Review
Chemistry, Multidisciplinary
Christian Hobson, Andrew N. Chan, Gerard D. Wright
Summary: The ongoing challenge of antibiotic resistance is a formidable threat towards the discovery and use of traditional antibiotics. The study and understanding of molecular mechanisms in the resistome provide a basis for the genomics-driven discovery and development of novel antimicrobials to combat emerging pathogens that are resistant to even the newest approved therapies.
Article
Biochemistry & Molecular Biology
Laura E. Holberger, Fernando Garza-Sanchez, James Lamoureux, David A. Low, Christopher S. Hayes
