scholarly journals Ethanol-induced stress response of Staphylococcus aureus

2017 ◽  
Vol 63 (9) ◽  
pp. 745-757 ◽  
Author(s):  
Jasmine M. Pando ◽  
Richard F. Pfeltz ◽  
Jesus A. Cuaron ◽  
Vijayaraj Nagarajan ◽  
Mukti N. Mishra ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Response ◽  
Protein Quality ◽  
Transcriptional Profiling ◽  
Stress Protein ◽  
Nucleotide Biosynthesis ◽  
Induced Stress ◽  
Stress Functions ◽  
Response Systems ◽  
Mrsa Strains

Transcriptional profiles of 2 unrelated clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates were analyzed following 10% (v/v) ethanol challenge (15 min), which arrested growth but did not reduce viability. Ethanol-induced stress (EIS) resulted in differential gene expression of 1091 genes, 600 common to both strains, of which 291 were upregulated. With the exception of the downregulation of genes involved with osmotic stress functions, EIS resulted in the upregulation of genes that contribute to stress response networks, notably those altered by oxidative stress, protein quality control in general, and heat shock in particular. In addition, genes involved with transcription, translation, and nucleotide biosynthesis were downregulated. relP, which encodes a small alarmone synthetase (RelP), was highly upregulated in both MRSA strains following ethanol challenge, and relP inactivation experiments indicated that this gene contributed to EIS growth arrest. A number of persistence-associated genes were also upregulated during EIS, including those that encode toxin–antitoxin systems. Overall, transcriptional profiling indicated that the MRSA investigated responded to EIS by entering a state of dormancy and by altering the expression of elements from cross protective stress response systems in an effort to protect preexisting proteins.

scholarly journals Identification and characterization of mutations responsible for the β-lactam resistance in oxacillin-susceptible mecA-positive Staphylococcus aureus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tanit Boonsiri ◽  
Shinya Watanabe ◽  
Xin-Ee Tan ◽  
Kanate Thitiananpakorn ◽  
Ryu Narimatsu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quality Control ◽  
Protein Quality ◽  
Stringent Response ◽  
Protein Quality Control ◽  
Purine Biosynthesis ◽  
Genome Comparison ◽  
Whole Genome ◽  
Intergenic Regions ◽  
Mrsa Strains

Abstract Staphylococcus aureus strains that are susceptible to the β-lactam antibiotic oxacillin despite carrying mecA (OS-MRSA) cause serious clinical problems globally because of their ability to easily acquire β-lactam resistance. Understanding the genetic mechanism(s) of acquisition of the resistance is therefore crucial for infection control management. For this purpose, a whole-genome sequencing-based analysis was performed using 43 clinical OS-MRSA strains and 100 mutants with reduced susceptibility to oxacillin (MICs 1.0–256 µg/mL) generated from 26 representative OS-MRSA strains. Genome comparison between the mutants and their respective parent strains identified a total of 141 mutations in 46 genes and 8 intergenic regions. Among them, the mutations are frequently found in genes related to RNA polymerase (rpoBC), purine biosynthesis (guaA, prs, hprT), (p)ppGpp synthesis (relSau), glycolysis (pykA, fbaA, fruB), protein quality control (clpXP, ftsH), and tRNA synthase (lysS, gltX), whereas no mutations existed in mec and bla operons. Whole-genome transcriptional profile of the resistant mutants demonstrated that expression of genes associated with purine biosynthesis, protein quality control, and tRNA synthesis were significantly inhibited similar to the massive transcription downregulation seen in S. aureus during the stringent response, while the levels of mecA expression and PBP2a production were varied. We conclude that a combination effect of mecA upregulation and stringent-like response may play an important role in acquisition of β-lactam resistance in OS-MRSA.

scholarly journals Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5265-5275 ◽  
Author(s):  
Eugene Khandros ◽  
Christopher S. Thom ◽  
Janine D'Souza ◽  
Mitchell J. Weiss
Keyword(s):  
Quality Control ◽  
Stress Response ◽  
Protein Quality ◽  
Transcriptional Profiling ◽  
Globin Gene ◽  
Gene Mutations ◽  
Protein Quality Control ◽  
Proteasome Inhibition ◽  
Protective Mechanisms

Cells remove unstable polypeptides through protein quality-control (PQC) pathways such as ubiquitin-mediated proteolysis and autophagy. In the present study, we investigated how these pathways are used in β-thalassemia, a common hemoglobinopathy in which β-globin gene mutations cause the accumulation and precipitation of cytotoxic α-globin subunits. In β-thalassemic erythrocyte precursors, free α-globin was polyubiquitinated and degraded by the proteasome. These cells exhibited enhanced proteasome activity, and transcriptional profiling revealed coordinated induction of most proteasome subunits that was mediated by the stress-response transcription factor Nrf1. In isolated thalassemic cells, short-term proteasome inhibition blocked the degradation of free α-globin. In contrast, prolonged in vivo treatment of β-thalassemic mice with the proteasome inhibitor bortezomib did not enhance the accumulation of free α-globin. Rather, systemic proteasome inhibition activated compensatory proteotoxic stress-response mechanisms, including autophagy, which cooperated with ubiquitin-mediated proteolysis to degrade free α-globin in erythroid cells. Our findings show that multiple interregulated PQC responses degrade excess α-globin. Therefore, β-thalassemia fits into the broader framework of protein-aggregation disorders that use PQC pathways as cell-protective mechanisms.

scholarly journals Comparative Analysis of the Roles of HtrA-Like Surface Proteases in Two Virulent Staphylococcus aureus Strains

2005 ◽  
Vol 73 (1) ◽  
pp. 563-572 ◽  
Author(s):  
Candice Rigoulay ◽  
José M. Entenza ◽  
David Halpern ◽  
Eleonora Widmer ◽  
Philippe Moreillon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rat Model ◽  
Stress Protein ◽  
Bacterial Survival ◽  
Slight Effect ◽  
Induced Stress ◽  
Bacterial Dissemination ◽  
Virulent Strains ◽  
Stress Survival ◽  
Insertion Mutants

ABSTRACT The HtrA surface protease is involved in the virulence of many pathogens, mainly by its role in stress resistance and bacterial survival. Staphylococcus aureus encodes two putative HtrA-like proteases, referred to as HtrA1 and HtrA2. To investigate the roles of HtrA proteins in S. aureus, we constructed htrA 1, htrA 2, and htrA 1 htrA 2 insertion mutants in two genetically different virulent strains, RN6390 and COL. In the RN6390 context, htrA 1 inactivation resulted in sensitivity to puromycin-induced stress. The RN6390 htrA 1 htrA 2 mutant was affected in the expression of several secreted virulence factors comprising the agr regulon. This observation was correlated with the disappearance of the agr RNA III transcript in the RN6390 htrA 1 htrA 2 mutant. The virulence of this mutant was diminished in a rat model of endocarditis. In the COL context, both HtrA1 and HtrA2 were essential for thermal stress survival. However, only HtrA1 had a slight effect on exoprotein expression. The htrA mutations did not diminish the virulence of the COL strain in the rat model of endocarditis. Our results indicate that HtrA proteins have different roles in S. aureus according to the strain, probably depending on specific differences in the regulation of virulence factor and stress protein expression. We propose that HtrA1 and HtrA2 contribute to pathogenicity by controlling the production of certain extracellular factors that are crucial for bacterial dissemination, as revealed in the RN6390 background. We speculate that HtrA proteins act in the agr-dependent regulation pathway by assuring folding and/or maturation of some surface components of the agr system.

Loading-Induced Stress Response in the Intervertebral Disc

2014 ◽  
Vol 4 (1_suppl) ◽  
pp. s-0034-1376604-s-0034-1376604
Author(s):  
W. H. Chooi ◽  
S. C. Chan ◽  
B. Gantenbein-Ritter ◽  
B. P. Chan
Keyword(s):  
Stress Response ◽  
Intervertebral Disc ◽  
Induced Stress

scholarly journals Efficiency of Antimicrobial Photodynamic Therapy with Photodithazine® on MSSA and MRSA Strains

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 869
Author(s):  
Beatriz Müller Nunes Souza ◽  
Juliana Guerra Pinto ◽  
André Henrique Correia Pereira ◽  
Alejandro Guillermo Miñán ◽  
Juliana Ferreira-Strixino
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
Antimicrobial Photodynamic Therapy ◽  
Bacterial Inactivation ◽  
Bacterial Reduction ◽  
Complete Inactivation ◽  
Opportunistic Bacteria ◽  
Significant Difference ◽  
Mrsa Strains

Staphylococccus aureus is a ubiquitous and opportunistic bacteria associated with high mortality rates. Antimicrobial photodynamic therapy (aPDT) is based on the application of a light source and a photosensitizer that can interact with molecular oxygen, forming Reactive Oxygen Species (ROS) that result in bacterial inactivation. This study aimed to analyze, in vitro, the action of aPDT with Photodithazine® (PDZ) in methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains. The strains were incubated with PDZ at 25, 50, 75, and 100 mg/L for 15 min and irradiated with fluences of 25, 50, and 100 J/cm2. The internalization of PDZ was evaluated by confocal microscopy, the bacterial growth by counting the number of colony-forming units, as well as the bacterial metabolic activity post-aPDT and the production of ROS. In both strains, the photosensitizer was internalized; the production of ROS increased when the aPDT was applied; there was a bacterial reduction compared to the control at all the evaluated fluences and concentrations; and, in most parameters, it was obtained complete inactivation with significant difference (p < 0.05). The implementation of aPDT with PDZ in clinical strains of S. aureus has resulted in its complete inactivation, including the MRSA strains.

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