Can antimicrobial blue light contribute to resistance development? Genome-wide analysis revealed aBL-protective genes in .

Increasing antibiotic resistance and the lack of new antibiotic-like compounds to combat bacterial resistance are significant problems of modern medicine. The development of new alternative therapeutic strategies is extremely important. Antimicrobial blue light (aBL) is an innovative approach to combat multidrug-resistant microorganisms.

Structural Insights into Antibacterial Payload Release from Gold Nanoparticles Bound to E. coli Peptide Deformylase.

The lack of new antibiotics and the rapidly rising number of pathogens resistant to antibiotics pose a serious problem to mankind. In bacteria, the cell membrane provides the first line of defence to antibiotics by preventing them from reaching their molecular target. To overcome this entrance barrier, it has been suggested that small Gold-Nanoparticles (AuNP) could possibly function as drug delivery systems for antibiotic ligands.

Physiology of trans-translation deficiency in Bacillus subtilis - a comparative proteomics study.

trans-Translation is the most effective ribosome rescue system known in bacteria. While it is essential in some bacteria, Bacillus subtilis possesses two additional alternative ribosome rescue mechanisms that require the proteins BrfA or RqcH. To investigate the physiology of trans-translation deficiency in the model organism B.

A Reinvestigation of the Role of the Sorbic Acid Tail on the Antibacterial and Anti-Tuberculosis Properties of Moiramide B.

Due to worldwide increasing resistances, there is a considerable need for antibacterial compounds with modes of action not yet realized in commercial antibiotics. One such promising structure is the acetyl-CoA carboxylase (ACC) inhibitor moiramide B which shows strong antibacterial activity against gram-positive bacteria such as Bacillus subtilis and weaker activities against gram-negative bacteria. However, the narrow structure-activity relationship of the pseudopeptide unit of moiramide B represents a formidable challenge for any optimization strategy.

Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance.

Antibiotic resistance is a major threat to global health; this problem can be addressed by the development of new antibacterial agents to keep pace with the evolutionary adaptation of pathogens. Computational approaches are essential tools to this end since their application enables fast and early strategical decisions in the drug development process. We present a rational design approach, in which acylide antibiotics were screened based on computational predictions of solubility, membrane permeability, and binding affinity toward the ribosome.

Zwitterionic Peptides Reduce Accumulation of Marine and Freshwater Biofilm Formers.

Zwitterionic peptides are facile low-fouling compounds for environmental applications as they are biocompatible and fully biodegradable as their degradation products are just amino acids. Here, a set of histidine (H) and glutamic acid (E), as well as lysine (K) and glutamic acid (E) based peptide sequences with zwitterionic properties were synthesized. Both oligopeptides (KE)K and (HE)H were synthesized in d and l configurations to test their ability to resist the nonspecific adsorption of the proteins lysozyme and fibrinogen.

Secondary metabolites released by the rhizosphere bacteria Arthrobacter oxydans and Kocuria rosea enhance plant availability and soil-plant transfer of germanium (Ge) and rare earth elements (REEs).

Here, we explore effects of metallophore-producing rhizobacteria on the plant availability of germanium (Ge) and rare earth elements (REEs). Five isolates of the four species Rhodococcus erythropolis, Arthrobacter oxydans, Kocuria rosea and Chryseobacterium koreense were characterized regarding their production of element-chelators using genome-mining, LC-MS/MS analysis and solid CAS-assay. Additionally, a soil elution experiment was conducted in order to identify isolates that increase solubility of Ge and REEs in soil solution.

Isolation and characterization of arsenic-binding siderophores from Rhodococcus erythropolis S43: role of heterobactin B and other heterobactin variants.

Rhodococcus erythropolis S43 is an arsenic-tolerant actinobacterium isolated from an arsenic contaminated soil. It has been shown to produce siderophores when exposed to iron-depleting conditions. In this work, strain S43 was shown to have the putative heterobactin production cluster htbABCDEFGHIJ(K).

Screening for Microbial Metal-Chelating Siderophores for the Removal of Metal Ions from Solutions.

To guarantee the supply of critical elements in the future, the development of new technologies is essential. Siderophores have high potential in the recovery and recycling of valuable metals due to their metal-chelating properties. Using the Chrome azurol S assay, 75 bacterial strains were screened to obtain a high-yield siderophore with the ability to complex valuable critical metal ions.

Photothermally Active Cryogel Devices for Effective Release of Antimicrobial Peptides: On-Demand Treatment of Infections.

There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage.

Applicability of Chromatographic Co-Elution for Antibiotic Target Identification.

Identification of the molecular target is a crucial step in evaluating novel antibiotics. To support target identification, a label-free method based on chromatographic co-elution has previously been developed. Target identification by chromatographic coelution (TICC) exploits the alteration of the elution profile of target-bound drug versus free drug in ion exchange (IEX) chromatography to identify potential target proteins from elution fractions.

Small Lipoprotein Atu8019 Is Involved in Selective Outer Membrane Vesicle (OMV) Docking to Bacterial Cells.

Outer membrane vesicles (OMVs), released from Gram-negative bacteria, have been attributed to intra- and interspecies communication and pathogenicity in diverse bacteria. OMVs carry various components including genetic material, toxins, signaling molecules, or proteins. Although the molecular mechanism(s) of cargo delivery is not fully understood, recent studies showed that transfer of the OMV content to surrounding cells is mediated by selective interactions.

Cultivation dependent formation of siderophores by Gordonia rubripertincta CWB2.

Herein we demonstrate cultivation-dependent siderophore production by the actinomycete Gordonia rubripertincta CWB2. The strain produces mostly citrate, but also desferrioxamine E (DFOE) and new hydroxamate-type siderophores. The production of hydroxamate-like siderophores is influenced by cultivation conditions, for example available carbon sources or presence of metals, such as the rare earth erbium or the heavy metal lead.

Data on metal-chelating, -immobilisation and biosorption properties by CWB2 in dependency on rare earth adaptation.

Recent studies have shown that the metal adaptation of Actinobacteria offers a rich source of metal inducible environmentally relevant bio-compounds and molecules. These interact through biosorption towards the unique cell walls or via metal chelating activity of metallophors with trace elements, heavy metals and even with lanthanides to overcome limitations and toxic concentrations. Herein, the purpose is to investigate the adaptation potential of CWB2 in dependence of the rare earths and to determine if we can utilize promising metallophore metal affinities for metal separation from aquatic solutions.

NifA is the master regulator of both nitrogenase systems in Rhodobacter capsulatus.

Rhodobacter capsulatus fixes atmospheric nitrogen (N ) by a molybdenum (Mo)-nitrogenase and a Mo-free iron (Fe)-nitrogenase, whose production is induced or repressed by Mo, respectively. At low nanomolar Mo concentrations, both isoenzymes are synthesized and contribute to nitrogen fixation. Here we examined the regulatory interplay of the central transcriptional activators NifA and AnfA by proteome profiling.

A Small Regulatory RNA Controls Cell Wall Biosynthesis and Antibiotic Resistance.

Small regulatory RNAs play an important role in the adaptation to changing conditions. Here, we describe a differentially expressed small regulatory RNA (sRNA) that affects various cellular processes in the plant pathogen Using a combination of bioinformatic predictions and comparative proteomics, we identified nine targets, most of which are positively regulated by the sRNA. According to these targets, we named the sRNA PmaR for peptidoglycan biosynthesis, motility, and ampicillin resistance regulator.

Fluorescent organometallic rhodium(I) and ruthenium(II) metallodrugs with 4-ethylthio-1,8-naphthalimide ligands: Antiproliferative effects, cellular uptake and DNA-interaction.

Fluorescent 4-ethylthio-1,8-naphthalimides containing rhodium(I) N-heterocyclic carbene (NHC) and ruthenium (II) NHC fragments were synthesised and evaluated for their antiproliferative effects, cellular uptake and DNA-binding activity. Both types of organometallics triggered ligand dependent efficient cytotoxic effects against tumor cells with the rhodium(I) NHC derivatives causing stronger effects than the ruthenium (II) NHC analogues. Antiproliferative effects could also be observed against several pathogenic Gram-positive bacterial strains, whereas the growth of Gram-negative bacteria was not substantially affected.

Purine biosynthesis is the bottleneck in trimethoprim-treated Bacillus subtilis.

Purpose: Trimethoprim is a folate biosynthesis inhibitor. Tetrahydrofolates are essential for the transfer of C units in several biochemical pathways including purine, thymine, methionine, and glycine biosynthesis. This study addressed the effects of folate biosynthesis inhibition on bacterial physiology.

Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines.

Allicin (diallyl thiosulfinate) from garlic is a highly potent natural antimicrobial substance. It inhibits growth of a variety of microorganisms, among them antibiotic-resistant strains. However, the precise mode of action of allicin is unknown.

Antimicrobial Peptides from the Aurein Family Form Ion-Selective Pores in Bacillus subtilis.

The mechanism of action of aurein 2.2 and aurein 2.3, antimicrobial peptides from the frog Litoria aurea, was investigated.

Activation of RidA chaperone function by N-chlorination.

Escherichia coli RidA is a member of a structurally conserved, yet functionally highly diverse protein family involved in translation inhibition (human), Hsp90-like chaperone activity (fruit fly) and enamine/imine deamination (Salmonella enterica). Here, we show that E. coli RidA modified with HOCl acts as a highly effective chaperone.

Inactivation of microbes and macromolecules by atmospheric-pressure plasma jets.

Plasma is ionized gas, which is found in various forms in nature and can also be generated artificially. A variety of cold atmospheric-pressure plasmas are currently being investigated for their clinical utility, and first studies reporting on the treatment of patients showed that plasma treatment may support the wound healing process. One of the benefits of plasma treatment is the effective inactivation of bacteria including tenacious pathogens such as Pseudomonas aeruginosa or multiresistant Staphylococcus aureus (MRSA).

Small cationic antimicrobial peptides delocalize peripheral membrane proteins.

Short antimicrobial peptides rich in arginine (R) and tryptophan (W) interact with membranes. To learn how this interaction leads to bacterial death, we characterized the effects of the minimal pharmacophore RWRWRW-NH2. A ruthenium-substituted derivative of this peptide localized to the membrane in vivo, and the peptide also integrated readily into mixed phospholipid bilayers that resemble Gram-positive membranes.

The lantibiotic NAI-107 binds to bactoprenol-bound cell wall precursors and impairs membrane functions.

The lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance (NMR). The lantibiotic efficiently interfered with late stages of cell wall biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N-acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm.

Analysis of the mechanism of action of potent antibacterial hetero-tri-organometallic compounds: a structurally new class of antibiotics.

Two hetero-tri-organometallic compounds with potent activity against Gram-positive bacteria including multi-resistant Staphylococcus aureus (MRSA) were identified. The compounds consist of a peptide nucleic acid backbone with an alkyne side chain, substituted with a cymantrene, a (dipicolyl)Re(CO)3 moiety, and either a ferrocene (FcPNA) or a ruthenocene (RcPNA). Comparative proteomic analysis indicates the bacterial membrane as antibiotic target structure.