SK-03-92 Drug Kills Intracellular .

Background: Tuberculosis affects millions of people worldwide. The emergence of drug-resistant strains has made treatment more difficult. A drug discovery project initiated to screen natural products identified a lead stilbene compound, and structure function analysis of hundreds of analogs led to the discovery of the SK-03-92 stilbene lead compound with activity against several non-tuberculoid mycobacteria.

Proline Transport and Growth Changes in Proline Transport Mutants of .

is a major cause of skin/soft tissue infections and more serious infections in humans. The species usually requires the importation of proline to be able to survive. Previous work has shown that single mutations in genes that encode for proline transporters affect the ability of to survive in vitro and in vivo.

Regulation of gene transcription by GadE and other acid tolerance gene products.

Uropathogenic (UPEC) cause millions of urinary tract infections each year in the United States. Type 1 pili are important for adherence of UPEC to uroepithelial cells in the human and murine urinary tracts where osmolality and pH vary. Previous work has shown that an acidic pH adversely affects the expression of type 1 pili.

GadE regulates gene transcription and motility in .

Background: () express flagella to ascend human urinary tracts. To survive in the acidic pH of human urine, uses the glutamate decarboxylase acid response system, which is regulated by the GadE protein.

Aim: To determine if growth in an acidic pH environment affected transcription and whether GadE regulated that transcription.

: Vector to an Increasing Diversity of Human Pathogens in the Upper Midwest.

Introduction: The black-legged tick, , is now recognized as the deadliest tick vector in the United States. The Upper Midwest, particularly Wisconsin and Minnesota, are endemic to a diversity of tick-transmitted infectious diseases. Although , the agent of Lyme disease, still accounts for the majority of diagnosed infections, is known to transmit other bacterial, viral, and parasitic agents.

Toxins: Armaments for a Significant Pathogen.

species are common inhabitants of humans and other animals [...

Regulation of the Staphylococcal Superantigen-Like Protein 1 Gene of Community-Associated Methicillin-Resistant in Murine Abscesses.

Community-associated methicillin-resistant (CA-MRSA) causes substantial skin and soft tissue infections annually in the United States and expresses numerous virulence factors, including a family of toxins known as the staphylococcal superantigen-like (SSL) proteins. Many of the SSL protein structures have been determined and implicated in immune system avoidance, but the full scope that these proteins play in different infection contexts remains unknown and continues to warrant investigation. Analysis of gene regulation may provide valuable information related to the function of these proteins.

Virulence factor landscape of a Staphylococcus aureus sequence type 45 strain, MCRF184.

Background: We describe the virulence factors of a methicillin-sensitive Staphylococcus aureus sequence type (ST) 45 strain, MCRF184, (spa type t917), that caused severe necrotizing fasciitis in a 72-year-old diabetic male. The genome of MCRF184 possesses three genomic islands: a relatively large type III νSaα with 42 open reading frames (ORFs) that includes superantigen- and lipoprotein-like genes, a truncated νSaβ that consists mostly of the enterotoxin gene cluster (egc), and a νSaγ island with 18 ORFs including α-toxin. Additionally, the genome has two phage-related regions: phage φSa3 with three genes of the immune evasion cluster (IEC), and an incomplete phage that is distinct from other S.

Differential Regulation of Genes following Binding to Mannose Receptors.

Regulation of the uropathogenic (UPEC) and genes was examined following type 1 pili binding to mannose-coated Sepharose beads. Within 25 min after mannose attachment, expression dropped eightfold, whereas transcription increased about two- to fourfold. Because both genes encode site-specific recombinases that affect the position of the element containing the promoter, the positioning of was also examined.

Temporal Regulation of Genes in Uropathogenic during Infection of the Murine Urinary Tract.

Uropathogenic (UPEC) adhere to cells in the human urinary tract via type 1 pili that undergo phase variation where a 314-bp DNA element flips between Phase-ON and Phase-OFF orientations through two site-specific recombinases, FimB and FimE. Three operon transcriptional fusions were created and moved into the clinical UPEC isolate NU149 to determine their temporal regulation in UPEC growing in the urinary tract. Within murine urinary tracts, the UPEC strains demonstrated elevated transcription of and early in the infection, but lower transcription by the fifth day in murine kidneys.

Management of methicillin-resistant mediated ventilator-associated pneumonia.

Prevention strategies and clinical management of methicillin- resistant (MRSA) infections in ventilated patients who develop ventilator-associated pneumonia (VAP) are important. Since MRSA are the most frequently isolated bacteria in patients with VAP, and a significant cause of morbidity and mortality in intubated patients, rapid diagnosis and early treatment could reduce mortality. This review will examine preventive steps (i.

Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray.

The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated .

Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus.

The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against . Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the thioredoxin reductase.

Osmolyte transport in and the role in pathogenesis.

Osmolyte transport is a pivotal part of bacterial life, particularly in high salt environments. Several low and high affinity osmolyte transport systems have been identified in various bacterial species. A lot of research has centered on characterizing the osmolyte transport systems of Gram-negative bacteria, but less has been done to characterize the same transport systems in Gram-positive bacteria.

Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92.

Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC (125 μg/ml) against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity ( altered gait, ungroomed, significant weight loss). Single dose (100 μg/g) pharmacokinetic (PK) analysis with formulated SK-03-92 showed that peak plasma concentration (1.

Design and synthesis of novel antimicrobials with activity against Gram-positive bacteria and mycobacterial species, including M. tuberculosis.

The alarming increase in bacterial resistance over the last decade along with a dramatic decrease in new treatments for infections has led to problems in the healthcare industry. Tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis which is responsible for 1.4 million deaths per year.

OmpR regulation of the uropathogenic Escherichia coli fimB gene in an acidic/high osmolality environment.

Uropathogenic Escherichia coli (UPEC) causes more than 90 % of all human urinary tract infections through type 1 piliated UPEC cells binding to bladder epithelial cells. The FimB and FimE site-specific recombinases orient the fimS element containing the fimA structural gene promoter. Regulation of fimB and fimE depends on environmental pH and osmolality.

Antibacterial spirobisnaphthalenes from the North American cup fungus Urnula craterium.

Urnucratins A-C (1-3), which possess an unusual bisnaphthospiroether skeleton with one oxygen bridge and one C-C bridge and represent a new subclass of bisnaphthalenes, were isolated from the North American cup fungus Urnula craterium. Their structures, including absolute configurations, were determined by means of HRMS, NMR, and quantum chemical CD calculations. Urnucratin A (1) was found to be active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Streptococcus pyogenes with MIC values of 2, 1, and 0.

Escherichia coli pyomyositis in an immunocompromised host.

Background: Pyomyositis due to Escherichia coli (E. coil) is rarely reported in immunocompromised patients with hematological malignancy.

Case Report: We present a case report of a 34-year-old man who developed E.

Regulation of genes in uropathogenic .

Uropathogenic (UPEC) is the leading cause of urinary tract infections in women, causing significant morbidity and mortality in this population. Adherence to host epithelial cells is a pivotal step in the pathogenesis of UPEC. One of the most important virulence factors involved in mediating this attachment is the type 1 pilus (type 1 fimbria) encoded by a set of genes arranged in an operon.

Synthesis and minimum inhibitory concentrations of SK-03-92 against Staphylococcus aureus and other gram-positive bacteria.

Staphylococcus aureus causes hundreds of thousands of infections and thousands of deaths per year in the United States. The emergence of methicillin-resistant S. aureus (MRSA), including community-associated methicillin-resistant S.

Mutational and transcriptional analyses of the Staphylococcus aureus low-affinity proline transporter OpuD during in vitro growth and infection of murine tissues.

Staphylococcus aureus continues to be a major health problem. This species' requirement for proline and proline transport from the extracellular environment is not well understood. Here, we identify a S.

Virulence genes and genotypic associations in nasal carriage, community-associated methicillin-susceptible and methicillin-resistant USA400 Staphylococcus aureus isolates.

It is not well understood why strains of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), a major cause of skin and soft tissue infections, became successful so quickly, overtaking the place of methicillin-sensitive S. aureus (MSSA) in many communities. To evaluate the genetic basis of differences in their virulence traits, 293 S.

A new class of potential anti-tuberculosis agents: Synthesis and preliminary evaluation of novel acrylic acid ethyl ester derivatives.

Novel acrylic acid ethyl ester derivatives were synthesized and evaluated as potential agents against Mycobacterium species. A versatile and efficient copper-catalyzed coupling process was developed and used to prepare a library of substituted acrylic acid ethyl ester analogs. Minimum inhibitory concentration assays indicated that two of these compounds 3 and 4 have greater in vitro activity against Mycobacterium smegmatis than rifampin, one of the current, first-line anti-mycobacterial chemotherapeutic agents.

Use of optical mapping to sort uropathogenic Escherichia coli strains into distinct subgroups.

Optical maps were generated for 33 uropathogenic Escherichia coli (UPEC) isolates. For individual genomes, the NcoI restriction fragments aligned into a unique chromosome map for each individual isolate, which was then compared with the in silico restriction maps of all of the sequenced E. coli and Shigella strains.