The Salmonella enterica EnvE is an Outer Membrane Lipoprotein and Its Gene Expression Leads to Transcriptional Repression of the Virulence Gene msgA.

The envE gene of Salmonella enterica serovar Typhimurium is encoded within Salmonella Pathogenicity Island-11 (SPI-11) and is located immediately upstream of the virulence gene msgA (macrophage survival gene A) in the same transcriptional orientation. To date, the characteristics and roles of envE remain largely unexplored. In this study, we show that EnvE, a predicted lipoprotein, is localized on the outer membrane using sucrose gradient ultracentrifugation.

Impact of small RNA RaoN on nitrosative-oxidative stress resistance and virulence of Salmonella enterica serovar Typhimurium.

RaoN is a Salmonella-specific small RNA that is encoded in the cspH-envE intergenic region on Salmonella pathogenicity island-11. We previously reported that RaoN is induced under conditions of acid and oxidative stress combined with nutrient limitation, contributing to the intramacrophage growth of Salmonella enterica serovar Typhimurium. However, the role of RaoN in nitrosative stress response and virulence has not yet been elucidated.

Direct interaction between the transcription factors CadC and OmpR involved in the acid stress response of Salmonella enterica.

In Salmonella enterica serovar Typhimurium, the acid-sensing regulator CadC activates transcription of the cadBA operon which contributes to the acid tolerance response. The DNA-binding response regulator OmpR in two-component regulatory system with EnvZ binds to its own promoter for autoinduction. We previously reported that CadC exerts a negative influence on ompR transcription during acid adaptation.

Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy.

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death.

Mutations in the primary sigma factor σA and termination factor rho that reduce susceptibility to cell wall antibiotics.

Combinations of glycopeptides and β-lactams exert synergistic antibacterial activity, but the evolutionary mechanisms driving resistance to both antibiotics remain largely unexplored. By repeated subculturing with increasing vancomycin (VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the model bacterium Bacillus subtilis with reduced susceptibility to both antibiotics. Whole-genome sequencing revealed point mutations in genes encoding the major σ factor of RNA polymerase (sigA), a cell shape-determining protein (mreB), and the ρ termination factor (rho).

Reducing the Level of Undecaprenyl Pyrophosphate Synthase Has Complex Effects on Susceptibility to Cell Wall Antibiotics.

Undecaprenyl pyrophosphate synthase (UppS) catalyzes the formation of the C lipid carrier (UPP) that is essential for bacterial peptidoglycan biosynthesis. We selected here a vancomycin (VAN)-resistant derivative of W168 that contains a single-point mutation in the ribosome-binding site of the gene designated Genetic reconstruction experiments demonstrate that the allele is sufficient to confer low-level VAN resistance and causes reduced UppS translation. The decreased level of UppS renders slightly more susceptible to many late-acting cell wall antibiotics, including β-lactams, but significantly more resistant to fosfomycin and d-cycloserine, antibiotics that interfere with the very early steps of cell wall synthesis.

RaoN, a small RNA encoded within Salmonella pathogenicity island-11, confers resistance to macrophage-induced stress.

Bacterial small non-coding RNAs act as important regulators that control numerous cellular processes. Here we identified RaoN, a novel small RNA encoded in the cspH-envE intergenic region on Salmonella pathogenicity island-11 (SPI-11). RaoN contributes to survival under conditions of acid and oxidative stress combined with nutrient limitation, which partially mimic the intramacrophage environment.

A mutation of the RNA polymerase β' subunit (rpoC) confers cephalosporin resistance in Bacillus subtilis.

In bacteria, mutations affecting the major catalytic subunits of RNA polymerase (encoded by rpoB and rpoC) emerge in response to a variety of selective pressures. Here we isolated a Bacillus subtilis strain with high-level resistance to cefuroxime (CEF). Whole-genome resequencing revealed only one missense mutation affecting an invariant residue in close proximity to the C-terminal DNA-binding domain of RpoC (G1122D).

A phosphotransferase system permease is a novel component of CadC signaling in Salmonella enterica.

In Salmonella enterica serovar Typhimurium, proteolytic cleavage of the membrane-bound transcriptional regulator CadC acts as a switch to activate genes of the lysine decarboxylase system in response to low pH and lysine signals. To identify the genetic factors required for the proteolytic activation of CadC, we performed genome-wide random mutagenesis. We show that a phosphotransferase system (PTS) permease STM4538 acts as a positive modulator of CadC function.

Glutamate dehydrogenase affects resistance to cell wall antibiotics in Bacillus subtilis.

The glutamate dehydrogenase RocG of Bacillus subtilis is a bifunctional protein with both enzymatic and regulatory functions. Here we show that the rocG null mutant is sensitive to β-lactams, including cefuroxime (CEF), and to fosfomycin but that resistant mutants arise due to gain-of-function mutations in gudB, which encodes an otherwise inactive glutamate dehydrogenase. In the presence of CEF, ΔrocG ΔgudB mutant cells exhibit growth arrest when they reach mid-exponential phase.

N,N-Dimethyl phytosphingosine sensitizes HL-60/MX2, a multidrug-resistant variant of HL-60 cells, to doxorubicin-induced cytotoxicity through ROS-mediated release of cytochrome c and AIF.

Doxorubicin (Dox) is widely used to treat a variety of tumors. However, resistance to this drug is common, making successful treatment more difficult. Previously, we introduced a novel phytosphingosine derivative, N,N-dimethyl phytosphingosine (DMPS), as a potent anticancer therapeutic agent in human leukemia cells.

The membrane-bound transcriptional regulator CadC is activated by proteolytic cleavage in response to acid stress.

Proteolytic processes often participate in signal transduction across bacterial membranes. In Salmonella enterica serovar Typhimurium, the transcriptional regulator CadC activates genes of lysine decarboxylase system in response to external acidification and exogenous lysine. However, the signaling mechanism of CadC activation remains unexplored.

CadC has a global translational effect during acid adaptation in Salmonella enterica serovar Typhimurium.

In Salmonella enterica serovar Typhimurium, the membrane-localized CadC is a transcriptional activator of the cadBA operon, which contributes to the acid tolerance response. Unlike in Escherichia coli, in which transcription of cadC is constitutive, in S. enterica serovar Typhimurium cadC expression is induced by low pH and lysine.