scholarly journals Staphylococcus aureus Regulator Sigma B is Important to Develop Chronic Infections in Hematogenous Murine Osteomyelitis Model

Pathogens ◽  
2017 ◽  
Vol 6 (3) ◽  
pp. 31 ◽  
Author(s):  
◽  
◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Chronic Infections ◽  
Sigma B

scholarly journals Transketolase is involved in the control of Sigma B during chronic infection by Staphylococcus aureus

2019 ◽  
Author(s):  
Xin Tan ◽  
Elodie Ramond ◽  
Anne Jamet ◽  
Baptiste Decaux-Tramoni ◽  
Marion Dupuis ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wild Type Strain ◽  
Pentose Phosphate ◽  
Chronic Infections ◽  
Master Regulators ◽  
Sigma B ◽  
Viable Bacteria ◽  
Infected Cells ◽  
Slow Growing

AbstractStaphylococcus aureus is a leading cause of both acute and chronic infections in humans. Its ability to persist within host cells is thought to play an important role in chronicity and treatment failures. The importance of the pentose phosphate pathway (PPP) during S. aureus chronic infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 (Δtkt) led to an impaired growth in broth. Using time-lapse video imaging, we correlated this phenotype with a defect in early intracellular proliferation compared to wild-type strain. As determined by metabolomic analysis, tkt inactivation also had an important impact on S. aureus metabolism. We then monitored long-term intracellular persistence over 10 days by counting of viable bacteria. Unexpectedly for such a slow-growing strain, the Δtkt mutant was almost completely eliminated by endothelial cells after ten days, as opposed to a prototypical slow-growing ΔhemDBL mutant for which we recovered 1,000 fold more viable bacteria. We found that in infected cells, the transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the Δtkt mutant compared to wild-type strain. Concomitantly, RNAIII transcription was strongly increased. This transcriptional profile is likely to explain the inability of this slow-growing mutant to sustain long-term intracellular survival, suggesting that TKT -or a functional PPP-is required for intracellular bacteria to enable a transcriptional program geared towards persistence.ImportanceStaphylococcus aureus is a leading cause of severe bacterial infections. This bacterium is readily internalized by non-professional phagocytes and infected cells have been proposed to play an important role in chronic infections and treatment failures.Here, we show the importance of the unique transketolase TKT of S. aureus USA300 in bacterial adaptation during chronic intracellular infection. We show that TKT is mandatory for the metabolomic homeostasis of S. aureus during intracellular persistence. This work unravels the critical role of TKT in the transcriptional regulation of the master regulators Sigma B, RpiRc and RNAIII linking the pentose phosphate pathway to the control of chronic S. aureus infections.

scholarly journals Transketolase of Staphylococcus aureus in the Control of Master Regulators of Stress Response During Infection

2019 ◽  
Vol 220 (12) ◽  
pp. 1967-1976
Author(s):  
Xin Tan ◽  
Elodie Ramond ◽  
Anne Jamet ◽  
Jean-Philippe Barnier ◽  
Baptiste Decaux-Tramoni ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Time Lapse ◽  
Pentose Phosphate ◽  
Host Cells ◽  
Chronic Infections ◽  
Gene Encoding ◽  
Master Regulators ◽  
Sigma B ◽  
Intracellular Proliferation ◽  
Major Defect

Abstract Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. In the current study, we focused on one key PPP enzyme, transketolase (TKT). We showed that inactivation of the unique gene encoding TKT activity in S. aureus USA300 (∆tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the ∆tkt strain compared with wild-type strain in early intracellular proliferation and in the ability to colonize kidneys. Transcriptional activity of the 2 master regulators sigma B and RpiRc was drastically reduced in the ∆tkt mutant during host cells invasion. The concomitant increased RNAIII transcription suggests that TKT—or a functional PPP—strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

sae is essential for expression of the staphylococcal adhesins Eap and Emp

Microbiology ◽  
2005 ◽  
Vol 151 (6) ◽  
pp. 1789-1800 ◽  
Author(s):  
Niamh Harraghy ◽  
Jan Kormanec ◽  
Christiane Wolz ◽  
Dagmar Homerova ◽  
Christiane Goerke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Extracellular Matrix ◽  
Virulence Factor ◽  
Eukaryotic Cells ◽  
Transcription Start Point ◽  
Chronic Infections ◽  
Transcription Start ◽  
Regulatory Mutants ◽  
Global Regulators ◽  
Glucose Analysis

Eap and Emp are two Staphylococcus aureus adhesins initially described as extracellular matrix binding proteins. Eap has since emerged as being important in adherence to and invasion of eukaryotic cells, as well as being described as an immunomodulator and virulence factor in chronic infections. This paper describes the mapping of the transcription start point of the eap and emp promoters. Moreover, using reporter-gene assays and real-time PCR in defined regulatory mutants, environmental conditions and global regulators affecting expression of eap and emp were investigated. Marked differences were found in expression of eap and emp between strain Newman and the 8325 derivatives SH1000 and 8325-4. Moreover, both genes were repressed in the presence of glucose. Analysis of expression of both genes in various regulatory mutants revealed that sarA and agr were involved in their regulation, but the data suggested that there were additional regulators of both genes. In a sae mutant, expression of both genes was severely repressed. sae expression was also reduced in the presence of glucose, suggesting that repression of eap and emp in glucose-containing medium may, in part, be a consequence of a decrease in expression of sae.

scholarly journals Sigma Factor SigB Is Crucial to Mediate Staphylococcus aureus Adaptation during Chronic Infections

2015 ◽  
Vol 11 (4) ◽  
pp. e1004870 ◽  
Author(s):  
Lorena Tuchscherr ◽  
Markus Bischoff ◽  
Santiago M. Lattar ◽  
Mariangeles Noto Llana ◽  
Henrike Pförtner ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sigma Factor ◽  
Chronic Infections

scholarly journals Protein A-Mediated Multicellular Behavior in Staphylococcus aureus

2008 ◽  
Vol 191 (3) ◽  
pp. 832-843 ◽  
Author(s):  
Nekane Merino ◽  
Alejandro Toledo-Arana ◽  
Marta Vergara-Irigaray ◽  
Jaione Valle ◽  
Cristina Solano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Protein A ◽  
Surface Proteins ◽  
Growth Media ◽  
Dependent Manner ◽  
Chronic Infections ◽  
The Matrix ◽  
Implanted Medical Devices ◽  
Biofilm Development

ABSTRACT The capacity of Staphylococcus aureus to form biofilms on host tissues and implanted medical devices is one of the major virulence traits underlying persistent and chronic infections. The matrix in which S. aureus cells are encased in a biofilm often consists of the polysaccharide intercellular adhesin (PIA) or poly-N-acetyl glucosamine (PNAG). However, surface proteins capable of promoting biofilm development in the absence of PIA/PNAG exopolysaccharide have been described. Here, we used two-dimensional nano-liquid chromatography and mass spectrometry to investigate the composition of a proteinaceous biofilm matrix and identified protein A (spa) as an essential component of the biofilm; protein A induced bacterial aggregation in liquid medium and biofilm formation under standing and flow conditions. Exogenous addition of synthetic protein A or supernatants containing secreted protein A to growth media induced biofilm development, indicating that protein A can promote biofilm development without being covalently anchored to the cell wall. Protein A-mediated biofilm formation was completely inhibited in a dose-dependent manner by addition of serum, purified immunoglobulin G, or anti-protein A-specific antibodies. A murine model of subcutaneous catheter infection unveiled a significant role for protein A in the development of biofilm-associated infections, as the amount of protein A-deficient bacteria recovered from the catheter was significantly lower than that of wild-type bacteria when both strains were used to coinfect the implanted medical device. Our results suggest a novel role for protein A complementary to its known capacity to interact with multiple immunologically important eukaryotic receptors.

scholarly journals Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing

2018 ◽  
Vol 115 (28) ◽  
pp. 7416-7421 ◽  
Author(s):  
Mohini Bhattacharya ◽  
Evelien T. M. Berends ◽  
Rita Chan ◽  
Elizabeth Schwab ◽  
Sashwati Roy ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
White Blood Cells ◽  
Neutrophil Extracellular Trap ◽  
Bacterial Survival ◽  
Chronic Infections ◽  
Burn Wound ◽  
Wound Model ◽  
Immune Defenses ◽  
Extracellular Trap

Bacterial biofilms efficiently evade immune defenses, greatly complicating the prognosis of chronic infections. How methicillin-resistant Staphylococcus aureus (MRSA) biofilms evade host immune defenses is largely unknown. This study describes some of the major mechanisms required for S. aureus biofilms to evade the innate immune response and provides evidence of key virulence factors required for survival and persistence of bacteria during chronic infections. Neutrophils are the most abundant white blood cells in circulation, playing crucial roles in the control and elimination of bacterial pathogens. Specifically, here we show that, unlike single-celled populations, S. aureus biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET) formation through the combined activity of leukocidins Panton–Valentine leukocidin and γ-hemolysin AB. By eliciting this response, S. aureus was able to persist, as the antimicrobial activity of released NETs was ineffective at clearing biofilm bacteria. Indeed, these studies suggest that NETs could inadvertently potentiate biofilm infections. Last, chronic infection in a porcine burn wound model clearly demonstrated that leukocidins are required for “NETosis” and facilitate bacterial survival in vivo.

scholarly journals PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 240 ◽  
Author(s):  
Adriana Vollaro ◽  
Anna Esposito ◽  
Eliana Pia Esposito ◽  
Raffaele Zarrilli ◽  
Annalisa Guaragna ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Surface Proteins ◽  
Transcriptional Analysis ◽  
Capsular Polysaccharides ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Concentration Dependent Manner ◽  
Expression Of Genes

Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.

scholarly journals d-Amino Acids Enhance the Activity of Antimicrobials against Biofilms of Clinical Wound Isolates of Staphylococcus aureus and Pseudomonas aeruginosa

2014 ◽  
Vol 58 (8) ◽  
pp. 4353-4361 ◽  
Author(s):  
Carlos J. Sanchez ◽  
Kevin S. Akers ◽  
Desiree R. Romano ◽  
Ronald L. Woodbury ◽  
Sharanda K. Hardy ◽  
...  
Keyword(s):  
Amino Acids ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Clinical Isolates ◽  
Chronic Infections ◽  
Content Type ◽  
Log Reduction ◽  
Viable Bacteria ◽  
Biofilm Bacteria

ABSTRACTWithin wounds, microorganisms predominantly exist as biofilms. Biofilms are associated with chronic infections and represent a tremendous clinical challenge. As antibiotics are often ineffective against biofilms, use of dispersal agents as adjunctive, topical therapies for the treatment of wound infections involving biofilms has gained interest. We evaluatedin vitrothe dispersive activity ofd-amino acids (d-AAs) on biofilms from clinical wound isolates ofStaphylococcus aureusandPseudomonas aeruginosa; moreover, we determined whether combinations ofd-AAs and antibiotics (clindamycin, cefazolin, oxacillin, rifampin, and vancomycin forS. aureusand amikacin, colistin, ciprofloxacin, imipenem, and ceftazidime forP. aeruginosa) enhance activity against biofilms.d-Met,d-Phe, andd-Trp at concentrations of ≥5 mM effectively dispersed preformed biofilms ofS. aureusandP. aeruginosaclinical isolates, an effect that was enhanced when they were combined as an equimolar mixture (d-Met/d-Phe/d-Trp). When combined withd-AAs, the activity of rifampin was significantly enhanced against biofilms of clinical isolates ofS. aureus, as indicated by a reduction in the minimum biofilm inhibitory concentration (MBIC) (from 32 to 8 μg/ml) and a >2-log reduction of viable biofilm bacteria compared to treatment with antibiotic alone. The addition ofd-AAs was also observed to enhance the activity of colistin and ciprofloxacin against biofilms ofP. aeruginosa, reducing the observed MBIC and the number of viable bacteria by >2 logs and 1 log at 64 and 32 μg/ml in contrast to antibiotics alone. These findings indicate that the biofilm dispersal activity ofd-AAs may represent an effective strategy, in combination with antimicrobials, to release bacteria from biofilms, subsequently enhancing antimicrobial activity.

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