scholarly journals The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus

2018 ◽  
Author(s):  
Megha Gulati ◽  
Jason M. Thomas ◽  
Mamta Rawat ◽  
Clarissa J. Nobile
Keyword(s):  
Nitric Oxide ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Nitrosative Stress ◽  
Host Responses ◽  
Host Immune System ◽  
Oxidative And Nitrosative Stress ◽  
Biofilm Thickness ◽  
Superficial Skin

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Our data show that the bshC mutant, which is defective in the last step of the bacillithiol pathway and lacks BSH, is impaired in biofilm formation. We also identify a putative S-nitrosobacillithiol reductase (BSNOR), similar to a S-nitrosomycothiol reductase found in M. smegmatis, and show that the BSNOR mutant has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that bacillithiol and nitric oxide are key players in normal biofilm formation in S. aureus.

scholarly journals Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mircea Radu Mihu ◽  
Vitor Cabral ◽  
Rodney Pattabhi ◽  
Moses T. Tar ◽  
Kelvin P. Davies ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Staphylococcus Aureus ◽  
Central Venous Catheter ◽  
Medical Devices ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Venous Catheter ◽  
Central Venous ◽  
Content Type ◽  
Nitric Oxide Releasing

ABSTRACT Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.

Biological Evaluation of Selected 1,2,3-triazole Derivatives as Antibacterial and Antibiofilm Agents

2020 ◽  
Vol 20 (24) ◽  
pp. 2186-2191
Author(s):  
Lialyz Soares Pereira André ◽  
Renata Freire Alves Pereira ◽  
Felipe Ramos Pinheiro ◽  
Aislan Cristina Rheder Fagundes Pascoal ◽  
Vitor Francisco Ferreira ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Biological Evaluation ◽  
Major Public Health Problem ◽  
Community Environments ◽  
Scanning Electron

Background: Resistance to antimicrobial agents is a major public health problem, being Staphylococcus aureus prevalent in infections in hospital and community environments and, admittedly, related to biofilm formation in biotic and abiotic surfaces. Biofilms form a complex and structured community of microorganisms surrounded by an extracellular matrix adhering to each other and to a surface that gives them even more protection from and resistance against the action of antimicrobial agents, as well as against host defenses. Methods: Aiming to control and solve these problems, our study sought to evaluate the action of 1,2,3- triazoles against a Staphylococcus aureus isolate in planktonic and in the biofilm form, evaluating the activity of this triazole through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. We have also performed cytotoxic evaluation and Scanning Electron Microscopy (SEM) of the biofilms under the treatment of the compound. The 1,2,3-triazole DAN 49 showed bacteriostatic and bactericidal activity (MIC and MBC 128 μg/mL). In addition, its presence interfered with the biofilm formation stage (1/2 MIC, p <0.000001) and demonstrated an effect on young preformed biofilm (2 MICs, p <0.05). Results: Scanning Electron Microscopy images showed a reduction in the cell population and the appearance of deformations on the surface of some bacteria in the biofilm under treatment with the compound. Conclusion: Therefore, it was possible to conclude the promising anti-biofilm potential of 1,2,3-triazole, demonstrating the importance of the synthesis of new compounds with biological activity.

scholarly journals Streptococcus mutans Lacking sufCDSUB Is Viable, but Displays Major Defects in Growth, Stress Tolerance Responses and Biofilm Formation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kassapa Ellepola ◽  
Xiaochang Huang ◽  
Ryan P. Riley ◽  
Jacob P. Bitoun ◽  
Zezhang Tom Wen
Keyword(s):  
Stress Tolerance ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Nitrosative Stress ◽  
Growth Stress ◽  
Low Ph ◽  
Luciferase Reporter ◽  
Deficient Mutant ◽  
Oxidative And Nitrosative Stress ◽  
Isoleucine Leucine

Streptococcus mutans appears to possess a sole iron-sulfur (Fe-S) cluster biosynthesis system encoded by the sufCDSUB cluster. This study was designed to examine the role of sufCDSUB in S. mutans physiology. Allelic exchange mutants deficient of the whole sufCDSUB cluster and in individual genes were constructed. Compared to the wild-type, UA159, the sufCDSUB-deficient mutant, Δsuf::kanr, had a significantly reduced growth rate, especially in medium with the absence of isoleucine, leucine or glutamate/glutamine, amino acids that require Fe-S clusters for biosynthesis and when grown with medium adjusted to pH 6.0 and under oxidative and nitrosative stress conditions. Relative to UA159, Δsuf::kanr had major defects in stress tolerance responses with reduced survival rate of &gt; 2-logs following incubation at low pH environment or after hydrogen peroxide challenge. When compared to UA159, Δsuf::kanr tended to form aggregates in broth medium and accumulated significantly less biofilm. As shown by luciferase reporter fusion assays, the expression of sufCDSUB was elevated by &gt; 5.4-fold when the reporter strain was transferred from iron sufficient medium to iron-limiting medium. Oxidative stress induced by methyl viologen increased sufCDSUB expression by &gt; 2-fold, and incubation in a low pH environment led to reduction of sufCDSUB expression by &gt; 7-fold. These results suggest that lacking of SufCDSUB in S. mutans causes major defects in various cellular processes of the deficient mutant, including growth, stress tolerance responses and biofilm formation. In addition, the viability of the deficient mutant also suggests that SUF, the sole Fe-S cluster machinery identified is non-essential in S. mutans, which is not known in any other bacterium lacking the NIF and/or ISC system. However, how the bacterium compensates the Fe-S deficiency and if any novel Fe-S assembly systems exist in this bacterium await further investigation.

scholarly journals Bacteriophage-Derived PeptidaseCHAPKEliminates and Prevents Staphylococcal Biofilms

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mark Fenton ◽  
Ruth Keary ◽  
Olivia McAuliffe ◽  
R. Paul Ross ◽  
Jim O'Mahony ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Bovine Mastitis ◽  
Economic Losses ◽  
Food Sector ◽  
Staphylococcal Infections ◽  
Prevention And Treatment

New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase,CHAPK, as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. PurifiedCHAPKapplied to biofilms ofStaphylococcus aureusDPC5246 completely eliminated the staphylococcal biofilms within 4 h. In addition,CHAPKwas able to prevent biofilm formation by this strain. TheCHAPKlysin also reducedS. aureusin a skin decolonization model. Our data demonstrates the potential ofCHAPKas a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors.

scholarly journals Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase

Gut ◽  
1999 ◽  
Vol 45 (2) ◽  
pp. 199-209 ◽  
Author(s):  
B Zingarelli ◽  
C Szabó ◽  
A L Salzman
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Experimental Colitis ◽  
Neutrophil Infiltration ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Oxidative And Nitrosative Stress ◽  
Intense Staining ◽  
Genetic Ablation

BACKGROUNDOxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases.AIMSTo study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis.METHODSTrinitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1).RESULTSTNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue.CONCLUSIONData show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.

Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1691-F1698 ◽  
Author(s):  
Cristino Cruz ◽  
Ricardo Correa-Rotter ◽  
Dolores Javier Sánchez-González ◽  
Rogelio Hernández-Pando ◽  
Perla D. Maldonado ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Renal Damage ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

scholarly journals Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Rhanany Alan Calloi Palozi ◽  
Maysa Isernhagen Schaedler ◽  
Cleide Adriane Signor Tirloni ◽  
Aniely Oliveira Silva ◽  
Francislaine Aparecida dos Reis Lívero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Folk Medicine ◽  
Thiobarbituric Acid ◽  
Ovariectomized Rats ◽  
Oxidative And Nitrosative Stress ◽  
Antihypertensive Response

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

scholarly journals Involvement of Nitric Oxide in Biofilm Dispersal of Pseudomonas aeruginosa

2006 ◽  
Vol 188 (21) ◽  
pp. 7344-7353 ◽  
Author(s):  
Nicolas Barraud ◽  
Daniel J. Hassett ◽  
Sung-Hei Hwang ◽  
Scott A. Rice ◽  
Staffan Kjelleberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Nitrosative Stress ◽  
Sodium Dodecyl ◽  
Anaerobic Respiration ◽  
Opportunistic Pathogen ◽  
No Donor ◽  
Biofilm Dispersal ◽  
Novel Strategy

ABSTRACT Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from P. aeruginosa biofilms. We demonstrate the involvement of anaerobic respiration processes in P. aeruginosa biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of P. aeruginosa biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a P. aeruginosa mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, ΔnirS) did not disperse, whereas a NO reductase mutant (ΔnorCB) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established P. aeruginosa biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections.

Oxidative and nitrosative stress in acute renal ischemia

2001 ◽  
Vol 281 (5) ◽  
pp. F948-F957 ◽  
Author(s):  
Eisei Noiri ◽  
Akihide Nakao ◽  
Koji Uchida ◽  
Hirokazu Tsukahara ◽  
Minoru Ohno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Reperfusion Period ◽  
Series Of Experiments ◽  
Acute Renal Ischemia ◽  
Oxide Synthase

First Published July 12, 2001; 10.1152/ajprenal.0071.2001.—Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS),l- N 6-(1-iminoethyl)lysine (l-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that l-Nil , lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

scholarly journals Alpha-Toxin Is Required for Biofilm Formation by Staphylococcus aureus

2003 ◽  
Vol 185 (10) ◽  
pp. 3214-3217 ◽  
Author(s):  
Nicky C. Caiazza ◽  
G. A. O'Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Clinical Settings ◽  
Alpha Toxin ◽  
Flow Conditions ◽  
Alpha Hemolysin ◽  
Integral Role ◽  
Hemolytic Toxin ◽  
Plastic Surfaces

ABSTRACT Staphylococcus aureus is a common pathogen associated with nosocomial infections. It can persist in clinical settings and gain increased resistance to antimicrobial agents through biofilm formation. We have found that alpha-toxin, a secreted, multimeric, hemolytic toxin encoded by the hla gene, plays an integral role in biofilm formation. The hla mutant was unable to fully colonize plastic surfaces under both static and flow conditions. Based on microscopy studies, we propose that alpha-hemolysin is required for cell-to-cell interactions during biofilm formation.

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