The Discovery and Development of Thienopyrimidines as Inhibitors of That Act through Inhibition of the Respiratory Complex I.

The successful treatment of infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against , a high-throughput screen identified two structurally related thienopyrimidine compounds that selectively inhibited over commensal members of the gut microbiota. To develop the structure-activity relationship (SAR) of the thienopyrimidines against , this study employed four series of modifications in which systematic substitution to the thienopyrimidine core was explored and ultimately side-chain elements optimized from the two original hits were merged into lead compounds.

Pharmacodynamics of ClpP-Activating Antibiotic Combinations against Gram-Positive Pathogens.

It is often difficult to cure endocarditis, osteomyelitis, and device-associated infections caused by Gram-positive pathogens, despite therapy with clinically appropriate antibiotics. This may be due to antibiotic tolerance or resistance development. Acyldepsipeptides (ADEPs) are a class of bactericidal compounds active against a variety of clinically important Gram-positive bacteria, including staphylococci, streptococci, and enterococci.

Beggiatoa leptomitoformis sp. nov., the first freshwater member of the genus capable of chemolithoautotrophic growth.

A strain of filamentous sulfur bacteria was isolated from freshwater spring contaminated with residential and agricultural wastewater in Moscow region, Russia. According to the results of phylogenetic analysis, strain D-402T belonged to the genus Beggiatoa within the family Beggiatoaceae of the class Gammaproteobacteria. Within the genus Beggiatoa, strain D-402T was most closely related to Beggiatoa alba strains.

Spirochaeta sinaica sp. nov., a halophilic spirochaete isolated from a cyanobacterial mat.

A strain of free-living obligately anaerobic, halophilic spirochaete, SLT, was isolated from a sample of a cyanobacterial mat of the hypersaline Solar Lake, Sinai shore. The strain had motile helical cells, 0.35-0.

TM7 detection in human microbiome: Are PCR primers and FISH probes specific enough?

TM7 appears important and omnipresent because it is repeatedly detected by molecular techniques in diverse environments. Here we report that most of primers and FISH probes thought to be TM7-specific do hybridize with multiple species from oral and vaginal cavity. This calls for re-examination of TM7 distribution and abundance.

In vitro and in vivo activities of HPi1, a selective antimicrobial against Helicobacter pylori.

A high-throughput screen (HTS) was performed to identify molecules specifically active against Helicobacter pylori, the causative agent of peptic ulcer and gastric carcinoma. Currently, treatment of H. pylori infection is suboptimal, with failure rates approaching 25%, despite triple therapy with two broad-spectrum antibiotics and a proton pump inhibitor or quadruple therapy with added bismuth.

Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.

Languishing antibiotic discovery and flourishing antibiotic resistance have prompted the development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against Mycobacterium tuberculosis and identify lassomycin, an antibiotic that exhibits potent bactericidal activity against both growing and dormant mycobacteria, including drug-resistant forms of M. tuberculosis, but little activity against other bacteria or mammalian cells.

Siderophores from neighboring organisms promote the growth of uncultured bacteria.

The majority of bacterial species do not grow on synthetic media. Many non-growers require growth factors from other bacteria, but the nature of these compounds is largely unknown. We show here that previously uncultured isolates from marine sediment biofilm grow on a Petri dish in the presence of cultured organisms from the same environment.

Spirochaeta perfilievii sp. nov., an oxygen-tolerant, sulfide-oxidizing, sulfur- and thiosulfate-reducing spirochaete isolated from a saline spring.

A novel strain of fermenting, aerotolerant, chemo-organoheterotrophic spirochaete designated P(T) was isolated from a sulfur 'Thiodendron' mat in a saline spring at the Staraya Russa resort (Novgorod Region, Russia). Cells of strain P(T) exhibited a helical shape. The spirochaete required sulfide in the growth medium and was able to oxidize it non-enzymically to elemental sulfur via the interaction of H(2)O(2) with sulfide and deposit it in the periplasmic space.

A trap for in situ cultivation of filamentous actinobacteria.

The approach of growing microorganisms in situ, or in a simulated natural environment is appealing, and different versions of it have been described by several groups. The major difficulties with these approaches are that they are not selective for actinomycetes - a group of gram-positive bacteria well known as a rich source of antibiotics. In order to efficiently access actinomycetes, a trap for specifically capturing and cultivating these microorganisms in situ has been developed, based on the ability of these bacteria to form hyphae and penetrate solid environments.

Proposal of Giesbergeria voronezhensis gen. nov., sp. nov. and G. kuznetsovii sp. nov. and reclassification of [Aquaspirillum] anulus, [A.] sinuosum and [A.] giesbergeri as Giesbergeria anulus comb. nov., G. sinuosa comb. nov. and G. giesbergeri comb. nov., and [Aquaspirillum] metamorphum and [A.] psychrophilum as Simplicispira metamorpha gen. nov., comb. nov. and S. psychrophila comb. nov.

Five Gram-negative, motile, spiral-shaped strains were isolated from a sulfide spring (D-412T), active sludge of wastewater (D-419T, D-420, D-424) and industrial wastewater (D-416). Comparative 16S rRNA gene sequence analysis showed that the isolates belong to the family Comamonadaceae, within the class Betaproteobacteria, but fall into a distinct cluster. On the basis of phenotypic, chemotaxonomic and phylogenetic data, a new genus, Giesbergeria gen.

A novel mannitol teichoic acid with side phosphate groups of Brevibacterium sp. VKM Ac-2118.

The cell wall of Brevibacterium sp. VKM Ac-2118 isolated from a frozen (mean annual temperature -12 degrees C) late Pliocene layer, 1.8-3 Myr, Kolyma lowland, Russia, contains mannitol teichoic acid with a previously unknown structure.

Okibacterium fritillariae gen. nov., sp. nov., a novel genus of the family Microbacteriaceae.

Okibacterium fritillariae gen. nov., sp.