Current status of pathogenetic mechanisms in staphylococcal arthritis

Tarkowski, Andrej; Bokarewa, Maria; Collins, L. Vincent; Gjertsson, Inger; Hultgren, Olof; Jin, Tao; Jonsson, Ing-Marie; Josefsson, Elisabet; Sakiniene, Egidija; Verdrengh, Margareta

doi:10.1111/j.1574-6968.2002.tb11466.x

Cited by 38 publications

(22 citation statements)

References 56 publications

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“…In experimental arthritis by S. aureus, mononuclear phagocytes migrate to the site of infection slightly later than neutrophils do. Macrophages are involved in the arthritic damage in this model, since mice depleted of monocytes/macrophages exhibit a significantly less severe arthritis (43). Similar studies have not been performed with Brucella, but a nonspecific inflammatory infiltrate has been found in synovial membrane and bone in patients with brucellar arthritis and osteomyelitis, respectively (28).…”

Section: Discussionmentioning

confidence: 60%

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection withBrucellaspp

2009

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Section: Discussionmentioning

confidence: 60%

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection withBrucellaspp

2009

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“…Arguably the most striking characteristic attributed to mutations in traP is the lack of virulence in animal models of infection (31). Therefore, we decided to test the mutation using our well-established model of murine septic arthritis (63) in an attempt to definitively attribute a role for TRAP in S. aureus pathogenesis. The choosing of this model is particularly pertinent as the TRAP antagonist RIP has been shown to protect mice from S. aureus infection in this very same model (4).…”

Section: Resultsmentioning

confidence: 99%

Inactivation of traP Has No Effect on the Agr Quorum-Sensing System or Virulence of Staphylococcus aureus

et al. 2007

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The success of Staphylococcus aureus as a pathogen can largely be attributed to the plethora of genetic regulators encoded within its genome that temporally regulate its arsenal of virulence determinants throughout its virulence lifestyle. Arguably the most important of these is the two-component, quorum-sensing system agr. Over the last decade, the controversial presence of a second quorum-sensing system (the TRAP system) has been proposed, and it has been mooted to function as the master regulator of virulence in S. aureus by modulating agr. Mutants defective in TRAP are reported to be devoid of agr expression, lacking in hemolytic activity, essentially deficient in the secretion of virulence determinants, and avirulent in infection models. A number of research groups have questioned the validity of the TRAP findings in recent years; however, a thorough and independent analysis of its role in S. aureus physiology and pathogenesis has not been forthcoming. Therefore, we have undertaken such an analysis of the TRAP locus of S. aureus. We found that a traP mutant was equally hemolytic as the wild-type strain. Furthermore, transcriptional profiling found no alterations in the traP mutant in expression levels of agr or in expression levels of multiple agr-regulated genes (hla, sspA, and spa). Analysis of secreted and surface proteins of the traP mutant revealed no deviation in comparison to the parent. Finally, analysis conducted using a murine model of S. aureus septic arthritis revealed that, in contrast to an agr mutant, the traP mutant was just as virulent as the wild-type strain.Staphylococcus aureus is a major human pathogen that is considered to be one of the most common causes of human disease (42). The success of S. aureus as an infectious agent is largely due to its ability to cause a wide range of infections in a plethora of ecological niches within the host. These can range from the relatively benign, such as soft tissue infections, boils, and abscesses, to the systemic and life threatening, such as endocarditis, septic arthritis, osteomyelitis, pneumonia, and septicemia. The array of pathologies caused by S. aureus is facilitated by the arsenal of virulence determinants encoded within its genome, all of which are tightly regulated both temporally and spatially throughout its pathogenic life cycle (42,51). This is achieved through an army of regulatory mechanisms that encompass DNA-binding proteins, two-component regulators, sigma factors, and quorum-sensing mechanisms (1, 3, 12, 15-18, 22, 26, 30, 32, 34, 51, 71).Arguably the most important of all of these regulatory loci is the agr system, a quorum-sensing two-component regulator that has been shown by numerous investigators to be central to the infectious capacity of S. aureus (1,34,47,49,55). Agr is a temporal regulatory element that is maximally expressed from the postexponential phase onwards, where it represses surface and attachment proteins and upregulates the synthesis of toxins and exoenzymes. Upon entry into stationary phase, agr expression...

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“…Staphylococcus aureus is the microorganism most frequently associated with bacterial arthritis (1,2), which results in synovial inflammation, cartilage and bone destruction, and eventually, joint deformity (3). The plasminogen activator (PA) system is a general proteolytic system that has been suggested to play an important role in the development of different types of arthritis (4)(5)(6).…”

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Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

Guo¹,

Li²,

Hagström³

et al. 2008

Arthritis & Rheumatism

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Objective. To assess the functional roles of plasmin in a murine model of Staphylococcus aureus-induced bacterial arthritis.Methods. Bacterial arthritis was induced in plasminogen-deficient (Plg -/-) and wild-type (Plg ؉/؉ ) littermates by local injection of 1 ؋ 10 6 colony-forming units of S aureus into the knee joints. Human plasminogen was administered to Plg -/-mice on days 0-7 or days 7-14. Antibiotic treatment was administered to Plg -/-mice on days 7-14. Bacteria counts and histologic, immunohistochemical, and Western blot analyses were performed.Results. In Plg ؉/؉ mice, S aureus counts had declined within 2 days, and by day 28 the bacteria had been completely eliminated. However, S aureus was still detectable in all injected joints from Plg -/-mice, and bacteria counts were 27 times higher than the amount injected on day 0. The extent of macrophage and neutrophil recruitment to the infected joints was comparable for Plg ؉/؉ and Plg -/-mice on days 1, 7, and 14. The activation of these inflammatory cells appeared to be impaired in Plg -/-mice, however. Treatment of Plg -/-mice with antibiotic (cloxacillin) resulted in successful killing of the bacteria, but the necrotic tissue remained in the infected joints. When human plasminogen was given intravenously to Plg -/-mice daily for 7 days, bacterial clearance was greatly improved as compared with their untreated counterparts, and the amount of necrotic tissue in the joint cavity was dramatically reduced. The expression of interleukin 6 (IL-6) and IL-10 was higher in Plg ؉/؉ mice than in Plg -/-mice during bacterial arthritis.Conclusion. Our findings indicate that plasmin plays a pluripotent role in protecting against S aureusinduced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression.Staphylococcus aureus is the microorganism most frequently associated with bacterial arthritis (1,2), which results in synovial inflammation, cartilage and bone destruction, and eventually, joint deformity (3). The plasminogen activator (PA) system is a general proteolytic system that has been suggested to play an important role in the development of different types of arthritis (4-6). Plasminogen can be activated to the broadspectrum protease plasmin by either of the 2 physiologic PAs, tissue-type PA (tPA) or urokinase-type PA (uPA). In addition to its function in fibrinolysis, plasmin(ogen) plays a role in degradation of the extracellular matrix (ECM) and in tissue remodeling during many physiologic and pathologic processes, such as wound healing (7), tumor cell invasion, angiogenesis, and rheumatoid arthritis (RA) (8). There is some evidence that plasmin can also induce proinflammatory responses independently of its proteolytic properties (9).A number of pathogenic microorganisms have been shown to bind plasminogen (10-12). The subsequent activation of plasminogen to plasmin may contribute to the virulence of these microorganisms (13). However, during bacterial arthritis, plasmin may also be of importance...

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Current status of pathogenetic mechanisms in staphylococcal arthritis

Cited by 38 publications

References 56 publications

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection withBrucellaspp

Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection withBrucellaspp

Inactivation of traP Has No Effect on the Agr Quorum-Sensing System or Virulence of Staphylococcus aureus

Protective effects of plasmin(ogen) in a mouse model of Staphylococcus aureus–induced arthritis

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