Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus

Microbiology ◽  
2011 ◽  
Vol 157 (3) ◽  
pp. 786-792 ◽  
Author(s):  
Takehisa Ohbayashi ◽  
Atsushi Irie ◽  
Yoji Murakami ◽  
Magdalena Nowak ◽  
Jan Potempa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Blood Clotting ◽  
Cysteine Proteases ◽  
Staphylococcal Infection ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Tissue Destruction ◽  
Clotting Disorder ◽  
Activity Dependent

Staphylococcus aureus is the most frequently isolated pathogen in Gram-positive sepsis often complicated by a blood clotting disorder, and is the leading cause of infective endocarditis induced by bacterial destruction of endocardial tissues. The bacterium secretes cysteine proteases referred to as staphopain A (ScpA) and staphopain B (SspB). To investigate virulence activities of staphopains pertinent to clotting disorders and tissue destruction, we examined their effects on collagen, one of the major tissue components, and on plasma clotting. Both staphopains prolonged the partial thromboplastin time of plasma in a dose- and activity-dependent manner, with SspB being threefold more potent than ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen, indicating that these enzymes can cause impaired plasma clotting through fibrinogen degradation. Whereas SspB cleaved the fibrinogen Aα-chain at the C-terminal region very efficiently, ScpA degraded it rather slowly. This explains the superior ability of the former enzyme to impair fibrinogen clottability. Enzymically active staphopains, at concentrations as low as 10 nM, degraded collagen with comparable efficiency. These results show novel virulence activities of staphopains in degrading fibrinogen and collagen, and suggest an involvement of staphopains in the clotting impairment and tissue destruction caused by staphylococcal infection.

scholarly journals Protease Activities Triggered by Ralstonia solanacearum Infection in Susceptible and Tolerant Tomato Lines

2018 ◽  
Vol 17 (6) ◽  
pp. 1112-1125 ◽  
Author(s):  
Marc Planas-Marquès ◽  
Martí Bernardo-Faura ◽  
Judith Paulus ◽  
Farnusch Kaschani ◽  
Markus Kaiser ◽  
...  
Keyword(s):  
Cysteine Proteases ◽  
Molecular Probes ◽  
Protein Profiling ◽  
Dependent Manner ◽  
Protein Activity ◽  
Tomato Plants ◽  
Bacterial Diseases ◽  
Susceptible Tomato ◽  
Activity Dependent ◽  
Leaf Apoplast

Activity-based protein profiling (ABPP) is a powerful proteomic technique to display protein activities in a proteome. It is based on the use of small molecular probes that react with the active site of proteins in an activity-dependent manner. We used ABPP to dissect the protein activity changes that occur in the intercellular spaces of tolerant (Hawaii 7996) and susceptible (Marmande) tomato plants in response to R. solanacearum, the causing agent of bacterial wilt, one of the most destructive bacterial diseases in plants. The intercellular space -or apoplast- is the first battlefield where the plant faces R. solanacearum. Here, we explore the possibility that the limited R. solanacearum colonization reported in the apoplast of tolerant tomato is partly determined by its active proteome. Our work reveals specific activation of papain-like cysteine proteases (PLCPs) and serine hydrolases (SHs) in the leaf apoplast of the tolerant tomato Hawaii 7996 on R. solanacearum infection. The P69 family members P69C and P69F, and an unannotated lipase (Solyc02g077110.2.1), were found to be post-translationally activated. In addition, protein network analysis showed that deeper changes in network topology take place in the susceptible tomato variety, suggesting that the tolerant cultivar might be more prepared to face R. solanacearum in its basal state. Altogether this work identifies significant changes in the activity of 4 PLCPs and 27 SHs in the tomato leaf apoplast in response to R. solanacearum, most of which are yet to be characterized. Our findings denote the importance of novel proteomic approaches such as ABPP to provide new insights on old and elusive questions regarding the molecular basis of resistance to R. solanacearum.

P2764Medical management of Staphylococcus aureus infective endocarditis: unexpectedly favourable outcomes in an aggressive disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C P Primus ◽  
M McCue ◽  
I Bvekerwa ◽  
E McGuire ◽  
K Wong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Medical Management ◽  
Surgical Intervention ◽  
Electronic Device ◽  
Significant Proportion ◽  
Venous Catheter ◽  
Similar Proportion ◽  
Tissue Destruction ◽  
Improved Outcomes

Abstract Introduction Early surgical intervention (ESI) for infective endocarditis (IE) is associated with improved outcomes. Staphylococcus aureus endocarditis (SAE) is associated with particularly high rates of tissue destruction, morbidity and mortality. However, the question as to whether ESI is mandated in all SAE continues to be debated, in both native (NVE) and prosthetic (PVE) endocarditis. Methods Retrospective review of all IE cases presenting to our institution from October 2015 to January 2019. IE was diagnosed following imaging and microbiological protocols as per ESC guidance, and data were extracted for those with SAE. Patients with isolated cardiac implantable electronic device IE or bacteraemia secondary to indwelling long-term venous catheter infection were excluded (non-valvular IE). Results Valvular IE was diagnosed in 411 patients overall; NVE in 286 (69.6%) and PVE in 125 (30.4%). S aureus was isolated in 111 patients (28.1%), of whom 5 had a Methicillin-resistant strain. SAE was confirmed in a similar proportion of NVE and PVE cases [83/111 (74.8%) and 28/111 (25.2%), respectively]. Surgical intervention was mandated in 35/83 with NVE (42.2%) and 11/28 (39.3%) with PVE, lower than in our overall cohort (55.9% and 48.8%, respectively). In-hospital SAE mortality was 16.2% overall (18.4% medical vs 13.0% surgical), and contributes a significant proportion to overall mortality (29% to medical & 26% to surgical mortality). Figure 1 identifies the cause of death per mode of treatment, highlighting the aggressive nature of S aureus infection (abscess, disseminated infection and septic shock; n=8), the importance of advanced non-cardiac comorbidity precluding intervention (n=3) and ongoing intravenous drug use in those with PVE (n=4). However, medical management was successful in 57.8% (38/83) of NVE and 60.7% (17/28) of PVE cases, both in hospital and to a minimum follow-up of 3-months. Conclusion Staphylococcus aureus is virulent and highly pathogenic, driving severe sepsis and advanced tissue destruction in SAE. Despite this, medical management can be successful when following international guidance, but requires co-ordinated care driven by a multidisciplinary IE team at a cardiothoracic centre.

scholarly journals 1606. Distinct Effectiveness of Oritavancin Against Tolerance-Induced Staphylococcus aureus

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S798
Author(s):  
Lauren Harven ◽  
Victoria Bingley ◽  
Andrew David Berti
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Recurrent Infection ◽  
Staphylococcal Infection ◽  
Polymorphonuclear Neutrophil ◽  
Aureus Strain ◽  
Dependent Manner ◽  
Antibiotic Exposure ◽  
Similar Extent ◽  
Bacterial Killing

Abstract Background Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. In Staphylococcus aureus this process can be sharply accelerated by multiple factors present during infection including nutrient limitation, host cationic peptide exposure and polymorphonuclear neutrophil internalization. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. Survivors of antibiotic exposure can restart cell division upon cessation of antibiotics and cause relapse or recurrent infection. In this study we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of tolerant Staphylococcus aureus bacteria. Methods S. aureus strain ATCC29213 as well as four clinical isolates (two MSSA, two MRSA) were selected for analysis. Overnight cultures were diluted in pre-warmed broth (MHB50) to 1×106 cfu/mL. Tolerance was induced by exposure to mupirocin (low [0.032 µg/mL] or high [3.2 µg/mL]) for 30 min. Tolerant cultures were exposed to vancomycin (35 µg/mL), cefazolin (25 µg/mL), daptomycin (7 µg/mL), telavancin (10 µg/mL), dalbavancin (6 µg/mL) or oritavancin (14 µg/mL) and viability was assessed by dilution plating at pre-defined time points (0, 2, 6, 24, 48 h). The minimum duration for 3-log viability reduction from baseline (MDK99.9) and culture viability at 48h were calculated independently for each of three biological replicates. Results The rate of bacterial killing (MDK99.9) was reduced for all study antibiotics by the addition of mupirocin in a dose-dependent manner. In contrast to all other regimens, including lipoglycopeptide comparators, oritavancin was the only antimicrobial agent that maintained a similar extent of bacterial killing against tolerant staphylococci. Conclusion Antimicrobial tolerant staphylococci exhibit a decreased rate of killing by antistaphylococcal agents. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of otritavancin against recurrent or relapse staphylococcal infection is warranted. Disclosures All Authors: No reported disclosures

scholarly journals Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin N. Nelson ◽  
Savannah G. Beakley ◽  
Sierra Posey ◽  
Brittney Conn ◽  
Emma Maritz ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Mammalian Cells ◽  
Cysteine Proteases ◽  
Dependent Manner ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen ◽  
Dose Dependent ◽  
Lysosomal Proteins

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.

scholarly journals Staphylococcus-associated acute glomerulonephritis in a patient with dermatomyositis

2021 ◽  
Vol 14 (1) ◽  
pp. e236695 ◽  
Author(s):  
Rasmi Ranjan Sahoo ◽  
Sourav Pradhan ◽  
Akhil Pawan Goel ◽  
Anupam Wakhlu
Keyword(s):  
Infective Endocarditis ◽  
Kidney Biopsy ◽  
Kidney Injury ◽  
Staphylococcal Infection ◽  
Left Knee ◽  
The Body ◽  
Acute Glomerulonephritis ◽  
Disease Course ◽  
Rheumatological Disease ◽  
Per Se

Staphylococcus-associated glomerulonephritis (SAGN) occurs as a complication of staphylococcal infection elsewhere in the body. Dermatomyositis (DM) can be associated with glomerulonephritis due to the disease per se. We report a case of a 40-year-old male patient with DM who presented with acute kidney injury, and was initially pulsed with methylprednisolone for 3 days, followed by dexamethasone equivalent to 1 mg/kg/day prednisolone. He was subsequently found to have SAGN on kidney biopsy along with staphylococcus bacteraemia and left knee septic arthritis. With proof of definitive infection, intravenous immunoglobulin 2 g/kg over 2 days was given and steroids were reduced. He was treated with intravenous vancomycin. With treatment, the general condition of the patient improved. On day 38, he developed infective endocarditis and died of congestive heart failure subsequently. Undiagnosed staphylococcal sepsis complicating a rheumatological disease course can lead to complications like SAGN, infective endocarditis and contribute to increased morbidity and mortality, as is exemplified by our case.

scholarly journals Infective endocarditis caused by HACEK group bacteria—a registry-based comparative study

2021 ◽  
Author(s):  
Anna Bläckberg ◽  
Christian Morenius ◽  
Lars Olaison ◽  
Andreas Berge ◽  
Magnus Rasmussen
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Mortality Rate ◽  
Haemophilus Influenzae ◽  
Comparative Study ◽  
Clinical Characteristics ◽  
Prosthetic Valve ◽  
Prosthetic Valve Endocarditis ◽  
Common Cause ◽  
Prosthetic Valves

AbstractInfective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low.

Infective endocarditis in patients who use IV drugs: a single centre cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Alraddadi ◽  
A Alsagheir ◽  
S Gao ◽  
K An ◽  
H Hronyecz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Long Term Outcomes ◽  
Replacement Surgery ◽  
Short Term Mortality ◽  
History Of ◽  
Short And Long Term ◽  
Baseline Characteristics

Abstract Background Managing endocarditis in intravenous drug use (IVDU) patients is challenging: unless patients successfully quit IVDU, the risk of re-infection is high. Clinicians often raise concerns with ethical and resource allocation principles when considering valve replacement surgery in this patient population. To help inform practice, we sought to determine the long-term outcomes of IVDU patients with endocarditis who underwent valve surgery in our center. Method After research ethics board approval, infective endocarditis cases managed surgically at our General Hospital between 2009 and 2018 were identified through the Cardiac Care Network. We reviewed patients' charts and included those with a history of IVDU in this study. We abstracted data on baseline characteristics, peri-operative course, short- and long-term outcomes. We report results using descriptive statistics. Results We identified 124 IVDU patients with surgically managed endocarditis. Mean age was 37 years (SD 11), 61% were females and 8% had redo surgery. During admission, 45% (n=56) of the patients had an embolic event: 63% pulmonary, 30% cerebral, 18% peripheral and 11% mesenteric. Causative organisms included Methicillin-Sensitive Staphylococcus Aureus (51%, n=63), Methicillin-Resistant Staphylococcus Aureus (15%, n=19), Streptococcus Viridans (2%, n=2), and others (31%, n=38). Emergency cardiac surgery was performed for 42% of patients (n=52). Most patients (84%) had single valve intervention: 53% tricuspid, 18% aortic and 13% mitral. Double valve interventions occurred in 15% (n=18). Overall, bioprosthetic replacement was most commonly chosen (79%, n=98). In-hospital mortality was 7% (n=8). Median length of stay in hospital was 13 days (IQR 8,21) and ICU 2 days (IQR 1,6). Mortality at longest available follow-up was 24% (n=30), with a median follow-up of 129 days (IQR 15,416). Valve reintervention rate was 11% (n=13) and readmission rate was 14% (n=17) at a median of 275 days (IQR 54,502). Conclusion Despite their critical condition, IVDU patients with endocarditis have good intra-hospital outcomes. Challenges occur after hospital discharge with loss of follow-up and high short-term mortality. IVDU relapse likely accounts for some of these issues. In-hospital and community comprehensive addiction management may improve these patients' outcomes beyond the surgical procedure. Annual rate 2009–2018 Funding Acknowledgement Type of funding source: None

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