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 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.

scholarly journals Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis

2015 ◽  
Author(s):  
Emilio Besada ◽  
Wenche Koldingsnes ◽  
Johannes C Nossent
Keyword(s):  
Staphylococcus Aureus ◽  
Maintenance Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Nasal Carriage ◽  
Chronic Infections ◽  
Disease Registry ◽  
Nasal Swabs ◽  
Median Period ◽  
Severe Infections

Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.

scholarly journals Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis

2015 ◽  
Author(s):  
Emilio Besada ◽  
Wenche Koldingsnes ◽  
Johannes C Nossent
Keyword(s):  
Staphylococcus Aureus ◽  
Maintenance Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Nasal Carriage ◽  
Chronic Infections ◽  
Disease Registry ◽  
Nasal Swabs ◽  
Median Period ◽  
Severe Infections

Objective: Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy. Methods: Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75 % of nasal swabs. Results: SA nasal carriage did not change during RTX (p=0.297). Persistent SA nasal carriage did not increase the risk of relapses (p=0.844) and of severe infections (p=0.144), but reduced the risk of chronic infections (p=0.044). Non-SA carriers were more prone to discontinue RTX due to hypogammaglobulinemia (p=0.122), since they had more profound decline of serum total Ig both after the first 2 g of RTX (p=0.079) and during RTX maintenance (p=0.063). Conclusion: Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not increase the risk of relapses and was associated with a lower risk of hypogammaglobulinemia associated chronic infections.

scholarly journals Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in Pseudomonas aeruginosa

2021 ◽  
Vol 9 (4) ◽  
pp. 753
Author(s):  
 Jingyi Zhou ◽  
Shouyi Li ◽  
Haozhou Li ◽  
Yongxin Jin ◽  
Fang Bai ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Nicotinamide Adenine Dinucleotide ◽  
Type Strain ◽  
Wild Type Strain ◽  
Toxin Gene ◽  
Type Ii ◽  
Wild Type ◽  
Chronic Infections ◽  
Dormant Cells ◽  
Slow Growing

Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a Pseudomonas aeruginosa wild-type strain PA14. Overexpression of a toxin gene PA14_51010 or deletion of the cognate antitoxin gene PA14_51020 increased the bacterial tolerance to antibiotics. Co-overexpression of PA14_51010 and PA14_51020 or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of PA14_51010 reduced the intracellular level of nicotinamide adenine dinucleotide (NAD+). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD+ level and promoting persister formation. In addition, overproduction of NAD+ by mutation in an nrtR gene counteracted the effect of PA14_51010 overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD+ level in P. aeruginosa.

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.

scholarly journals Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanan Shi ◽  
Jingjing Zhu ◽  
Yan Xu ◽  
Xiaozhao Tang ◽  
Zushun Yang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Energy Metabolism ◽  
Active Sites ◽  
Current Knowledge ◽  
Tricarboxylic Acid Cycle ◽  
Protein A ◽  
Pentose Phosphate ◽  
Post Translational Modification ◽  
Bacterial Physiology ◽  
Dihydrolipoyl Dehydrogenase

Abstract Background Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen. Results Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position − 1 and alanine at + 2 and + 4 positions was high. KEGG pathway analysis showed that six categories were highly enriched, including ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain protein, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC, and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes. Conclusions Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate the potential roles of protein malonylation in bacterial physiology and metabolism.

scholarly journals Hidradenoma papilliferum of the hymen: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ozer Birge ◽  
Mehmet Sait Bakır ◽  
Ceyda Karadag ◽  
Zivar Eldarova ◽  
Tayup Simsek
Keyword(s):  
Benign Neoplasm ◽  
Surgical Removal ◽  
Apocrine Glands ◽  
Sexually Transmitted ◽  
Anogenital Region ◽  
Hidradenoma Papilliferum ◽  
Anogenital Area ◽  
Slow Growing

Abstract Background Hidradenoma papilliferum is a rare benign neoplasm arising from apocrine glands. It occurs commonly on the anogenital region of middle-aged women. It usually presents as a slow growing, solitary asymptomatic, skin colored or red nodule less than 1 cm in diameter. Case presentation The case is a 38-year-old, white woman who presented with a painful nodule occurring within a month in the himenal region of the posterior vaginal introitus. The nodule was excisied and the histology revealed a hidradenoma papilliferum. The diagnosis and treatment of hidradenoma papilliferum is possible with surgical removal and histopathological evaluation of nodules. Conclusion When an adult woman presents with a noduler lesion in the anogenital area, sexually transmitted diseases and other benign and malignant vulvar lesions, as well as malignant transformation is very rare but,should be kept in mind; however because it has been reported and long-term clinical follow-up is suggested

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