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Yuanyuan Dai, Wenjiao Chang, Changcheng Zhao, Jing Peng, Liangfei Xu, Huaiwei Lu, Shusheng Zhou, Xiaoling Ma
Acquisition of vancomycin resistance in Staphylococcus aureus is often accompanied by a reduction in virulence, but the mechanisms underlying this change remain unclear. The present study was undertaken to investigate this process in a clinical heterogeneous vancomycin-intermediate S. aureus (hVISA) strain 10827, a hVISA reference strain Mu3 and a VISA reference strain Mu50, along with their respective series of vancomycin-induced resistant strains. In these strains, increasing MICs of vancomycin were associated with increased expression of vancomycin resistance-associated regulator gene (vraR), and decreased expression of virulence genes (hla, hlb and coa) and virulence-regulated genes (RNAIII, agrA and saeR)...
March 13, 2017: Antimicrobial Agents and Chemotherapy
Josephine C Moran, Jamal A Alorabi, Malcolm J Horsburgh
Staphylococcal colonization of human skin is ubiquitous, with particular species more frequent at different body sites. Whereas Staphylococcus epidermidis can be isolated from the skin of every individual tested, Staphylococcus aureus is isolated from <5% of healthy individuals. The factors that drive staphylococcal speciation and niche selection on skin are incompletely defined. Here we show that S. aureus is inhibited to a greater extent than S. epidermidis by the sebaceous lipid sapienic acid, supporting a role for this skin antimicrobial in selection of skin staphylococci...
2017: Frontiers in Microbiology
Van Chi Thai, Teck Kwang Lim, Kim Phuong Uyen Le, Qingsong Lin, Thi Thu Hoai Nguyen
OBJECTIVES: The aim of this study was to compare global protein expression changes during fluoroquinolone (FQ) exposure of Staphylococcus aureus. METHODS: Total protein extracts of wild-type S. aureus ATCC 29213 and six multidrug-resistant (MDR) strains derived from the wild-type under different FQ exposures were analysed using the 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) method combined with LC-MS/MS analysis. Differentially expressed proteins were searched for their Gene Ontology (GO) annotation (UniProt database) and protein-protein interaction network (STRING v...
December 27, 2016: Journal of Global Antimicrobial Resistance
Christina N Krute, Kelly C Rice, Jeffrey L Bose
In previous studies, we identified the fatty acid kinase virulence factor regulator B (VfrB) as a potent regulator of α-hemolysin and other virulence factors in Staphylococcus aureus In this study, we demonstrated that VfrB is a positive activator of the SaeRS two-component regulatory system. Analysis of vfrB, saeR, and saeS mutant strains revealed that VfrB functions in the same pathway as SaeRS. At the transcriptional level, the promoter activities of SaeRS class I (coa) and class II (hla) target genes were downregulated during the exponential growth phase in the vfrB mutant, compared to the wild-type strain...
March 1, 2017: Journal of Bacteriology
Mara Baldry, Anita Nielsen, Martin S Bojer, Yu Zhao, Cathrine Friberg, Dan Ifrah, Nina Glasser Heede, Thomas O Larsen, Hanne Frøkiær, Dorte Frees, Lixin Zhang, Huanqin Dai, Hanne Ingmer
Staphylococcus aureus is a serious human pathogen and antibiotic resistant, community-associated strains, such as the methicillin resistant S. aureus (MRSA) strain USA300, continue to spread. To avoid resistance, anti-virulence therapy has been proposed where toxicity is targeted rather than viability. Previously we have shown that norlichexanthone, a small non-reduced tricyclic polyketide produced by fungi and lichens, reduces expression of hla encoding α-hemolysin as well as the regulatory RNAIII of the agr quorum sensing system in S...
2016: PloS One
Jacob E Choby, Laura A Mike, Ameya A Mashruwala, Brendan F Dutter, Paul M Dunman, Gary A Sulikowski, Jeffrey M Boyd, Eric P Skaar
The rising problem of antimicrobial resistance in Staphylococcus aureus necessitates the discovery of novel therapeutic targets for small-molecule intervention. A major obstacle of drug discovery is identifying the target of molecules selected from high-throughput phenotypic assays. Here, we show that the toxicity of a small molecule termed '882 is dependent on the constitutive activity of the S. aureus virulence regulator SaeRS, uncovering a link between virulence factor production and energy generation. A series of genetic, physiological, and biochemical analyses reveal that '882 inhibits iron-sulfur (Fe-S) cluster assembly most likely through inhibition of the Suf complex, which synthesizes Fe-S clusters...
November 17, 2016: Cell Chemical Biology
Tyler K Nygaard, Scott D Kobayashi, Brett Freedman, Adeline R Porter, Jovanka M Voyich, Michael Otto, Olaf Schneewind, Frank R DeLeo
Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S...
2016: PloS One
Saer Samanipour, Katherine Langford, Malcolm J Reid, Kevin V Thomas
Gas chromatography coupled with high resolution time of flight mass spectrometry (GC-HR-TOFMS) has gained popularity for the target and suspect analysis of complex samples. However, confident detection of target/suspect analytes in complex samples, such as produced water, remains a challenging task. Here we report on the development and validation of a two stage algorithm for the confident target and suspect analysis of produced water extracts. We performed both target and suspect analysis for 48 standards, which were a mixture of 28 aliphatic hydrocarbons and 20 alkylated phenols, in 3 produced water extracts...
September 9, 2016: Journal of Chromatography. A
Jinxin Zhao, Soon-Ee Cheah, Kade D Roberts, Roger L Nation, Philip E Thompson, Tony Velkov, Zongjun Du, Matthew D Johnson, Jian Li
Polymyxin B and colistin are exclusively active against Gram-negative pathogens and have been used in the clinic as a last-line therapy. In this study, we investigated the antimicrobial activity of a novel polymyxin, FADDI-019, against Staphylococcus aureus. MIC and time-kill assays were employed to measure the activity of FADDI-019 against S. aureus ATCC 700699. Cell morphology was examined with scanning electron microscopy (SEM), and cell membrane polarity was measured using flow cytometry. Transcriptome changes caused by FADDI-019 treatment were investigated using transcriptome sequencing (RNA-Seq)...
July 2016: MSphere
Miren L Baroja, Christine A Herfst, Katherine J Kasper, Stacey X Xu, Daniel A Gillett, Jingru Li, Gregor Reid, John K McCormick
UNLABELLED: Toxic shock syndrome toxin 1 (TSST-1) is a Staphylococcus aureus superantigen that has been implicated in both menstrual and nonmenstrual toxic shock syndrome (TSS). Despite the important role of TSST-1 in severe human disease, a comprehensive understanding of staphylococcal regulatory factors that control TSST-1 expression remains incomplete. The S. aureus exotoxin expression (Sae) operon contains a well-characterized two-component system that regulates a number of important exotoxins in S...
October 1, 2016: Journal of Bacteriology
Nicola J Smyllie, Violetta Pilorz, James Boyd, Qing-Jun Meng, Ben Saer, Johanna E Chesham, Elizabeth S Maywood, Toke P Krogager, David G Spiller, Raymond Boot-Handford, Michael R H White, Michael H Hastings, Andrew S I Loudon
Transcriptional-translational feedback loops (TTFLs) are a conserved molecular motif of circadian clocks. The principal clock in mammals is the suprachiasmatic nucleus (SCN) of the hypothalamus. In SCN neurons, auto-regulatory feedback on core clock genes Period (Per) and Cryptochrome (Cry) following nuclear entry of their protein products is the basis of circadian oscillation [1, 2]. In Drosophila clock neurons, the movement of dPer into the nucleus is subject to a circadian gate that generates a delay in the TTFL, and this delay is thought to be critical for oscillation [3, 4]...
July 25, 2016: Current Biology: CB
Gregory S Orf, Rafael G Saer, Dariusz M Niedzwiedzki, Hao Zhang, Chelsea L McIntosh, Jason W Schultz, Liviu M Mirica, Robert E Blankenship
Light-harvesting antenna complexes not only aid in the capture of solar energy for photosynthesis, but regulate the quantity of transferred energy as well. Light-harvesting regulation is important for protecting reaction center complexes from overexcitation, generation of reactive oxygen species, and metabolic overload. Usually, this regulation is controlled by the association of light-harvesting antennas with accessory quenchers such as carotenoids. One antenna complex, the Fenna-Matthews-Olson (FMO) antenna protein from green sulfur bacteria, completely lacks carotenoids and other known accessory quenchers...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Fermin E Guerra, Conrad B Addison, Nienke W M de Jong, Joseph Azzolino, Kyler B Pallister, Jos A G van Strijp, Jovanka M Voyich
Neutrophils are the first line of defense after a pathogen has breached the epithelial barriers, and unimpaired neutrophil functions are essential to clear infections. Staphylococcus aureus is a prevalent human pathogen that is able to withstand neutrophil killing, yet the mechanisms used by S. aureus to inhibit neutrophil clearance remain incompletely defined. The production of reactive oxygen species (ROS) is a vital neutrophil antimicrobial mechanism. Herein, we test the hypothesis that S. aureus uses the SaeR/S two-component gene regulatory system to produce virulence factors that reduce neutrophil ROS production...
November 2016: Journal of Leukocyte Biology
Tzu-Ping Ko, Cheng-Yang Huang, Tung-Ju Hsieh, Sheng-Chia Chen, Yu-Ren Chen, Chia-Shin Yang, Hao-Cheng Kuo, Wen-Lung Wang, Tzu-Hung Hsiao, Ching-Heng Lin, Yeh Chen
Two-component system SaeRS of Staphylococcus regulates virulence factor expression through phosphorylation of the DNA-binding regulator SaeR by the sensor histidine kinase SaeS. Here crystal structures of the DNA-binding domain (DBD) of SaeR from two Staphylococcal species Staphylococcus epidermidis and Staphylococcus aureus were determined and showed similar folds. Analyzing the DNA binding activity of three mutants of SeSaeR, we observed that Thr217 is important in binding to the phosphate group of DNA and Trp219 may interact with the base pairs...
June 10, 2016: Biochemical and Biophysical Research Communications
Rafael Saer, Gregory S Orf, Xun Lu, Hao Zhang, Matthew J Cuneo, Dean A A Myles, Robert E Blankenship
The Fenna-Matthews-Olson (FMO) pigment-protein complex in green sulfur bacteria transfers excitation energy from the chlorosome antenna complex to the reaction center. In understanding energy transfer in the FMO protein, the individual contributions of the bacteriochlorophyll pigments to the FMO complex's absorption spectrum could provide detailed information with which molecular and energetic models can be constructed. The absorption properties of the pigments, however, are such that their spectra overlap significantly...
September 2016: Biochimica et Biophysica Acta
Qiang Lou, Yuanfang Ma, Di Qu
Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, the S. epidermidis SaeRS was identified to negatively regulate the expression of genes involved in competence (comF, murF), cytolysis (lrgA), and autolysis (lytS) by DNA microarray or real-time RT-PCR analysis. In addition, saeRS mutant showed increased competence and higher susceptibility to antibiotics such as penicillin and oxacillin than the wild-type strain...
April 2016: Journal of Basic Microbiology
Zachary R Tranchemontagne, Ryan B Camire, Vanessa J O'Donnell, Jessfor Baugh, Kristin M Burkholder
Methicillin-resistant Staphylococcus aureus (MRSA) causes invasive, drug-resistant skin and soft tissue infections. Reports that S. aureus bacteria survive inside macrophages suggest that the intramacrophage environment may be a niche for persistent infection; however, mechanisms by which the bacteria might evade macrophage phagosomal defenses are unclear. We examined the fate of the S. aureus-containing phagosome in THP-1 macrophages by evaluating bacterial intracellular survival and phagosomal acidification and maturation and by testing the impact of phagosomal conditions on bacterial viability...
January 2016: Infection and Immunity
Xiaojiao Fan, Xu Zhang, Yuwei Zhu, Liwen Niu, Maikun Teng, Baolin Sun, Xu Li
The SaeR/S two-component regulatory system is essential for controlling the expression of many virulence factors in Staphylococcus aureus. SaeR, a member of the OmpR/PhoB family, is a response regulator with an N-terminal regulatory domain and a C-terminal DNA-binding domain. In order to elucidate how SaeR binds to the promoter regions of target genes, the crystal structure of the DNA-binding domain of SaeR (SaeR(DBD)) was solved at 2.5 Å resolution. The structure reveals that SaeR(DBD) exists as a monomer and has the canonical winged helix-turn-helix module...
August 2015: Acta Crystallographica. Section D, Biological Crystallography
Fan Zhao, Brian L Cheng, Susan Boyle-Vavra, Maria-Luisa Alegre, Robert S Daum, Anita S Chong, Christopher P Montgomery
Recurrent Staphylococcus aureus skin and soft tissue infections (SSTIs) are common despite detectable antibody responses, leading to the belief that the immune response elicited by these infections is not protective. We recently reported that S. aureus USA300 SSTI elicits antibodies that protect against recurrent SSTI in BALB/c but not C57BL/6 mice, and in this study, we aimed to uncover the specificity of the protective antibodies. Using a proteomic approach, we found that S. aureus SSTI elicited broad polyclonal antibody responses in both BALB/c and C57BL/6 mice and identified 10 S...
September 2015: Infection and Immunity
Hoonsik Cho, Do-Won Jeong, Qian Liu, Won-Sik Yeo, Thomas Vogl, Eric P Skaar, Walter J Chazin, Taeok Bae
Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression...
July 2015: PLoS Pathogens
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