Associative learning of non-nestmate cues improves enemy recognition in ants.

Recognition protects biological systems at all scales, from cells to societies. Social insects recognize their nestmates by colony-specific olfactory labels that individuals store as neural templates in their memory. Throughout an ant's life, learning continuously shapes the nestmate recognition template to keep up with the constant changes in colony labels.

In vitro spectrum of activity of finafloxacin, a novel, pH-activated fluoroquinolone, under standard and acidic conditions.

Finafloxacin is a novel fluoroquinolone that exhibits enhanced antibacterial activity under acidic conditions. The aim of this study was to define the in vitro pH-activity relationship. Finafloxacin exhibited optimal antibacterial activity between pH 5.

Determination of moxifloxacin anaerobic susceptibility breakpoints according to the Clinical and Laboratory Standards Institute guidelines.

A summary of the key data presented to Clinical and Laboratory Standards Institute (CLSI, formerly National Committee for Clinical and Laboratory Standards) in determination of moxifloxacin anaerobic breakpoints is presented. The breakpoint analysis required review of a variety of data, including bacteriologic and clinical outcomes by MIC of anaerobic isolates from prospective clinical trials in patients with complicated intra-abdominal infections, human and animal pharmacokinetic/pharmacodynamic (PK/PD) information and in vitro models, MIC distributions of indicated organisms, and animal model efficacy data for strains with MIC values around prospective breakpoints. The compilation of the various components of this breakpoint analysis supports the US Food and Drug Administration (FDA) and CLSI moxifloxacin anaerobic breakpoints of < or =2 mg/L (susceptible), 4 mg/L (intermediate), and > or =8 mg/L (resistant), and provides information to European investigators for interpretation of MICs prior to establishment of the European Committee on Antimicrobial Susceptibility Testing breakpoints.

Novel bacterial acetyl coenzyme A carboxylase inhibitors with antibiotic efficacy in vivo.

The pseudopeptide pyrrolidinedione antibiotics, such as moiramide B, have recently been discovered to target the multisubunit acetyl coenzyme A (acetyl-CoA) carboxylases of bacteria. In this paper, we describe synthetic variations of each moiety of the modularly composed pyrrolidinediones, providing insight into structure-activity relationships of biochemical target activity, in vitro potency, and in vivo efficacy. The novel derivatives showed highly improved activities against gram-positive bacteria compared to those of previously reported variants.

Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.

Here we show that a new class of antibiotics-acyldepsipeptides-has antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection. The acyldepsipeptides are active against isolates that are resistant to antibiotics in clinical application, implying a new target, which we identify as ClpP, the core unit of a major bacterial protease complex. ClpP is usually tightly regulated and strictly requires a member of the family of Clp-ATPases and often further accessory proteins for proteolytic activation.

New class of bacterial phenylalanyl-tRNA synthetase inhibitors with high potency and broad-spectrum activity.

Phenylalanyl (Phe)-tRNA synthetase (Phe-RS) is an essential enzyme which catalyzes the transfer of phenylalanine to the Phe-specific transfer RNA (tRNA(Phe)), a key step in protein biosynthesis. Phenyl-thiazolylurea-sulfonamides were identified as a novel class of potent inhibitors of bacterial Phe-RS by high-throughput screening and chemical variation of the screening hit. The compounds inhibit Phe-RS of Escherichia coli, Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus, with 50% inhibitory concentrations in the nanomolar range.

Pyrimidinone antibiotics--heterocyclic analogues with improved antibacterial spectrum.

We report the synthesis and pharmacological evaluation of new derivatives of the natural dipeptide antibiotic TAN 1057 A,B containing heterocycles either in the beta-amino acid side chain or as mimics of the urea function. In the course of this program, we identified novel analogues that display activity towards a broader panel of Gram-positive bacteriae.

Altersetin, a new antibiotic from cultures of endophytic Alternaria spp. Taxonomy, fermentation, isolation, structure elucidation and biological activities.

A novel antibacterial antibiotic, for which the name altersetin is proposed, was isolated from the culture broth of two endophytic Alternaria species. The relative and absolute configuration were assigned by NOESY or CD data, respectively. Altersetin is chemically related to equisetin and showed potent MIC against several pathogenic gram-positive bacteria, whereas gram-negative bacteria and pathogenic yeast were not or much less susceptible.

Dihydropyrimidinones--a new class of anti-staphylococcal antibiotics.

We report the synthesis and pharmacological evaluation of new derivatives of natural dipeptide antibiotic TAN-1057 A, B. In the course of this program, we identified novel analogues of the natural product that display similar antibacterial activity and showed improved tolerability.

Straightforward syntheses of furanomycin derivatives and their biological evaluation.

Several types of furanomycin analogues were synthesized and investigated with respect to their antibacterial activity. Two different synthetic pathways were developed, based on aldol reactions/ring closing metathesis and an ester enolate Claisen rearrangement. Only the natural product and its desmethyl derivative showed antibacterial activity, pointing towards a narrow structure-activity relationship.

Novel antibiotics for the treatment of gram-positive bacterial infections.

The natural dipeptide antibiotic TAN 1057 A,B displays excellent antibacterial activity against staphylococci including methicillin resistant Staphylococcus aureus. However, the in vitro activity against additional Gram-positive strains, in particular pneumococci and Enterococcus faecalis, proved to be considerably lower. We report the synthesis and pharmacological evaluation of new derivatives of this natural product that displayed increased antibacterial potency against staphylococci and were also active against pneumococci.

Synthesis and biological evaluation of vancomycin dimers with potent activity against vancomycin-resistant bacteria: target-accelerated combinatorial synthesis.

Based on the notion that dimerization and/or variation of amino acid 1 of vancomycin could potentially enhance biological activity, a series of synthetic and chemical biology studies were undertaken in order to discover potent antibacterial agents. Herein we describe two ligation methods (disulfide formation and olefin metathesis) for dimerizing vancomycin derivatives and applications of target-accelerated combinatorial synthesis (e.g.

Solid- and solution-phase synthesis of vancomycin and vancomycin analogues with activity against vancomycin-resistant bacteria.

Vancomycin, the prototypical member of the glycopeptide family of antibiotics, is a clinically used antibiotic employed against a variety of drug-resistant bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA). The recent emergence of vancomycin resistance, viewed as a growing threat to public health, prompted us to initiate a program aimed at restoring the potency of this important antibiotic through chemical manipulation of the vancomycin structure. Herein, we describe the development of synthetic technology based on the design of a novel selenium safety catch linker, application of this technology to a solid-phase semisynthesis of vancomycin, and the solid- and solution-phase synthesis of vancomycin libraries.

seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties.

seco-Cyclothialidines are a promising class of bacterial DNA gyrase B subunit inhibitors. A new seco-cyclothialidine derivative containing a dioxazine moiety, BAY 50-7952, was synthesized through a new concise pathway. One key step of the synthesis is the straightforward formation of the 2-aminothiazole derivative of S-tritylcysteine.

Ribosomal RNA is the target for oxazolidinones, a novel class of translational inhibitors.

Oxazolidinones are antibacterial agents that act primarily against gram-positive bacteria by inhibiting protein synthesis. The binding of oxazolidinones to 70S ribosomes from Escherichia coli was studied by both UV-induced cross-linking using an azido derivative of oxazolidinone and chemical footprinting using dimethyl sulphate. Oxazolidinone binding sites were found on both 30S and 50S subunits, rRNA being the only target.

In vitro activity of BAY 12-8039, a new 8-methoxyquinolone.

BAY 12-8039 is a new 8-methoxyquinolone with antibacterial activity against gram-positive bacteria which is significantly better than those of sparfloxacin or ciprofloxacin. The minimal inhibitory concentrations (MICs) for 90% of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis were 0.062 and 2 mg/l, respectively.

In vitro evaluation of BAY Y3118, a new full-spectrum fluoroquinolone.

BAY Y3118, 1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- chloro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid hydrochloride, is a new fluoroquinolone with antibacterial activity against an expanded spectrum of species including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, and also anaerobes such as Bacteriodes fragilis and Clostridium perfringens.

Effect of ciprofloxacin on stationary bacteria studied in vivo in a murine granuloma pouch model infected with Escherichia coli.

A granuloma pouch model in mice was used to investigate the effect of ciprofloxacin in vivo on cells of Escherichia coli (Neumann) under stationary growth conditions. The animals were treated up to three times intraperitoneally with 2.5, 10 or 40 mg/kg ciprofloxacin 24 h after infection.

[Synthesis of a disaccharide with antibiotic activity].

The aminodisaccharide glycoside methyl 2,4-diamino-2,4-dideoxy-6-O-(2,6-diamino-2,6-dideoxy-alpha-D-glucopyranosyl)- beta-D-glucopyranoside (4), which exhibits a structural resemblance to neamine, was synthesized via the azido method. Starting from 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide, the alpha-D-glycosylation of O-6 of methyl 2,4-diazido-3-O-benzyl-2,4-dideoxy-beta-D-glucopyranoside was accomplished stereoselectively at low temperatures in the presence of mercury bromide. Against some gram-negative test-organisms, the activity of 4 was found to be in the same range as neamine, but directed against different germs.