Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment.

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown.

Physalin H, physalin B, and isophysalin B suppress the quorum-sensing function of by binding to AgrA.

The virulence of , including methicillin-resistant (MRSA), depends on the expression of toxins and virulence factors controlled by the quorum-sensing (QS) system, encoded on the virulence accessory gene regulator () locus. The aim of this study was to identify a phytochemical that inhibits Agr-QS function and to elucidate its mechanism. We screened 577 compounds and identified physalin H, physalin B, and isophysalin B--phytochemicals belonging to physalins found in plants of the Solanaceae family--as novel Agr-QS modulators.

New biflavonoids isolated from Xylia kerrii leaves extract with selective cytotoxicity against MH7A human rheumatoid arthritis synovial fibroblast cells.

Three new biflavonoids (1-3) and two known flavonoids (4, 5) were isolated from Xylia kerrii collected in Thailand. Compounds 1-5 showed selective cytotoxicity against the rheumatoid fibroblast-like synovial MH7A cell line, and these compounds showed weak cytotoxicity against the human lung synovial fibroblast WI-38 VA13 sub 2 RA cell line. Notably, compound 1 was highly selective toward MH7A cells with an IC value of 6.

Total Synthesis of Dragmacidins G and H.

The total synthesis of dragmacidins G and H was achieved for the first time by employing nucleophilic aromatic substitution and site-selective cross-coupling reactions using appropriately functionalized pyrazines as substrates. The evaluation of antibacterial activities of dragmacidin G, dragmacidin H, and synthetic analogues against and the efflux pump-deficient Typhimurium revealed that the presence of a Br group on the indole ring adjacent to the sulfide unit was important for increasing antibacterial activities.

High-Efficiency Single-Cell Containment Microdevices Based on Fluid Control.

In this study, we developed a comb-shaped microfluidic device that can efficiently trap and culture a single cell (bacterium). Conventional culture devices have difficulty in trapping a single bacterium and often use a centrifuge to push the bacterium into the channel. The device developed in this study can store bacteria in almost all growth channels using the flowing fluid.

Two Bioactive Compounds, Uniformides A and B, Isolated from a Culture of IFM0856 in the Presence of Animal Cells.

Two new peptides named uniformides A and B ( and , respectively) were isolated from the cultured extracts of IFM0856 in the presence of mouse macrophage-like cell line J774.1, in modified Czapek-Dox medium. These compounds were not produced in a culture containing only but in one that also included J774.

Identification of the Inhibitory Compounds for Metallo-β-lactamases and Structural Analysis of the Binding Modes.

Metallo-β-lactamases (MBLs) are significant threats to humans because they deteriorate many kinds of β-lactam antibiotics and are key enzymes responsible for multi-drug resistance of bacterial pathogens. As a result of in vitro screening, two compounds were identified as potent inhibitors of two kinds of MBLs: imipenemase (IMP-1) and New Delhi metallo-β-lactamase (NDM-1). The binding structure of one of the identified compounds was clarified by an X-ray crystal analysis in complex with IMP-1, in which two possible binding poses were observed.

Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development.

Atopic dermatitis (AD) is commonly associated with colonization by in the affected skin. To understand the role of in the development of AD, we performed whole-genome sequencing of strains isolated from the cheek skin of 268 Japanese infants 1 and 6 months after birth. About 45% of infants were colonized with at 1 month regardless of AD outcome.

Exploration of Salmonella effector mutant strains on MTR4 and RRP6 degradation.

Salmonella enterica serovar Typhimurium (Salmonella), a pathogenic bacterium, is a major cause of foodborne diseases worldwide. Salmonella injects multiple virulence factors, called effectors, into cells and causes multiple rearrangements of cellular biological reactions that are important for Salmonella proliferation and virulence. Previously, we reported that Salmonella infection causes loss of MTR4 and RRP6, which are nuclear RNA degradation factors, resulting in the stabilization and accumulation of unstable nuclear RNAs.

Humoral Immunity vs. .

In primary infection with , it has been reported-without consideration of 's functions-that humoral immunity plays no role in the clearance of bacteria. In fact, targets and suppresses several aspects of humoral immunity, including B cell lymphopoiesis, B cell activation, and IgG production. In particular, the suppression of IgG-secreting plasma cell maintenance allows the persistence of in tissues.

SiiE prevents an efficient humoral immune memory by interfering with IgG plasma cell persistence in the bone marrow.

Serum IgG, which is mainly generated from IgG-secreting plasma cells in the bone marrow (BM), protects our body against various pathogens. We show here that the protein SiiE of is both required and sufficient to prevent an efficient humoral immune memory against the pathogen by selectively reducing the number of IgG-secreting plasma cells in the BM. Attenuated SiiE-deficient induces high and lasting titers of specific and protective -specific IgG and qualifies as an efficient vaccine against A SiiE-derived peptide with homology to laminin β1 is sufficient to ablate IgG-secreting plasma cells from the BM, identifying laminin β1 as a component of niches for IgG-secreting plasma cells in the BM, and furthermore, qualifies it as a unique therapeutic option to selectively ablate IgG-secreting plasma cells in autoimmune diseases and multiple myeloma.

Chaperone-mediated secretion switching from early to middle substrates in the type III secretion system encoded by pathogenicity island 2.

The bacterial type III secretion system (T3SS) delivers virulence proteins, called effectors, into eukaryotic cells. T3SS comprises a transmembrane secretion apparatus and a complex network of specialized chaperones that target protein substrates to this secretion apparatus. However, the regulation of secretion switching from early (needle and inner rod) to middle (tip/filament and translocators) substrates is incompletely understood.

Diminished nuclear RNA decay upon infection upregulates antibacterial noncoding RNAs.

Cytoplasmic mRNA degradation controls gene expression to help eliminate pathogens during infection. However, it has remained unclear whether such regulation also extends to nuclear RNA decay. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) such as NEAT1v2, are stabilized upon infection in HeLa cells.

Membrane vesicle protein PagC as a novel biomarker for detecting pathogenic Salmonella in the viable but not culturable state.

The viable but non-culturable (VBNC) state is a remarkable survival mechanism in which cells exist in a physiologically inactive state. Bacteria in the VBNC state do not form colonies, and thus, are difficult to detect using colony-based methods. As a result, VBNC bacteria are potentially virulent and can cause widespread contamination during food production.

Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan.

Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g.

RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility.

Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmA(II) enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmA(II), rendering TEL susceptibility.

[Molecular targets of bacterial effectors and toxins that underlie vulnerability to diseases].

Pathogenic bacteria produce a variety of effectors and/or toxins, which subvert target cell/tissue functions in the infected hosts. Some of those effectors/toxins also perturb host defense mechanism, thereby making up more complicated pathophysiological conditions. Such bacterial effectors/toxins may have been positively selected during evolution because they directly strike vulnerable points in the host system.

Molecular characterization of linezolid-resistant CoNS isolates in Japan.

Objectives: Linezolid has been reported to remain active against 98% of staphylococci with resistance identified in 0.05% of Staphylococcus aureus and 1.4% of CoNS.

FliT selectively enhances proteolysis of FlhC subunit in FlhD4C2 complex by an ATP-dependent protease, ClpXP.

We previously reported that the ClpXP ATP-dependent protease specifically recognizes and degrades the flagellar master transcriptional activator complex, FlhD4C2, to negatively control flagellar biogenesis. The flagellum-related protein, FliT, is also a negative regulator of flagellar regulon by inhibiting the binding of FlhD4C2 to the promoter DNA. We have found a novel pathway of FliT inhibition of FlhD4C2 activity connected to ClpXP proteolysis.

Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin susceptible.

Several posttranscriptional modifications of bacterial rRNAs are important in determining antibiotic resistance or sensitivity. In all Gram-positive bacteria, dimethylation of nucleotide A2058, located in domain V of 23S rRNA, by the dimethyltransferase Erm(B) results in low susceptibility and resistance to telithromycin (TEL). However, this is insufficient to produce high-level resistance to TEL in Streptococcus pneumoniae.

YdiV: a dual function protein that targets FlhDC for ClpXP-dependent degradation by promoting release of DNA-bound FlhDC complex.

YdiV is an EAL-like protein that acts as a post-transcriptional, negative regulator of the flagellar master transcriptional activator complex, FlhD(4)C(2), in Salmonella enterica to couple flagellar gene expression to nutrient availability. Mutants defective in ClpXP protease no longer exhibit YdiV-dependent inhibition of FlhD(4)C(2)-dependent transcription under moderate YdiV expression conditions. ClpXP protease degrades FlhD(4)C(2), and this degradation is accelerated in the presence of YdiV.

Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria.

Background: Many pathogens use a type III secretion system to translocate virulence proteins (called effectors) in order to adapt to the host environment. To date, many prediction tools for effector identification have been developed. However, these tools are insufficiently accurate for producing a list of putative effectors that can be applied directly for labor-intensive experimental verification.