Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids

Christensson, Bértil; Gilbart, James William; Fox, Alvin; Morgan, Stephen L.

doi:10.1002/anr.1780321012

Cited by 30 publications

(12 citation statements)

References 14 publications

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“…and mass spectrometry). Christensson et al [66] found their method only sensitive enough to detect 4 x I ()7 staphylococci per milliliter when compared to quan titative cultures in septic arthritis. The detection of ex ploded cocci by light microscopy is easily capable of iden tifying about 200 explodeds per milliliter, and thus it is far more sensitive than the most sensitive physicochemical methods thus far used.…”

Section: Relevance O F Explodeds Found In Urine To Systemic Diseasementioning

confidence: 99%

A Urinary Marker for Occult Systemic Coccal Disease

Hyman

1994

Nephron

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Gram-negative particles, found in ‘normal’ urine by an improved microscopic technique, become excessive (often > 10⁵/ml) in many systemic diseases. In these diseases they are accompanied by sparse, usually fastidious, gram-positive cocci. Antibiotics at moderate doses usually have little effect. Larger doses of antibiotics suppress, or temporarily eliminate, the particles. In this report, the particles are characterized by light microscopy for better identification. Then, by detection of muramic acid in a hydrolysate and by transmission electron microscopy, they are identified as decomposed (‘exploded’) gram-positive cocci. Since explodeds cannot be external contaminants, and their precursors cannot proliferate sufficiently in urine, they must have crossed renal membranes to come from within the body. They are demonstrated in tissue fluids and in synovial fluids by optical microscopy, by their muramic acid, and by transmission electron microscopy. Thus, they cross other membranes. Explodeds are excessive in several rheumatic diseases, in renal diseases, in diseases in which a coccal cause has been sought, and in some in which cocci have never been considered. There is no precedent for explodeds. Their appearance and numbers are compatible with the literature on natural and experimental systemic streptococcal diseases and with the experimental illnesses following injection of streptococcal cell walls. Urinary explodeds are likely to be the end result of the ‘almost physiological’ entry of streptococci into the circulation which necessitates predental antibiotic prophylaxis in mitral disease. Increased numbers of urinary explodeds probably represent excessive entry of precursors or proliferation of precursors within the host. Urinary explodeds serve as a marker for diverse systemic diseases, systemic coccal disease.

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Section: Relevance O F Explodeds Found In Urine To Systemic Diseasementioning

confidence: 99%

A Urinary Marker for Occult Systemic Coccal Disease

Hyman

1994

Nephron

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“…In reactive arthritis, muramic acid was found in 2 of 14 synovial fluid specimens; however, in the vast majority the levels were so low that detection proved elusive (30). Muramic acid has not been found in noninfected control synovial fluids (7,16,30).…”

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confidence: 97%

“…For example, one complication of gram-negative bacillary dysentery can be a reactive arthritis (4,6,21,22,33). Detection of muramic acid in synovial fluids from patients with septic arthritis demonstrates the utility of nontraditional techniques for evaluation of the presence of bacteria in human tissue (7,16,30). In reactive arthritis, muramic acid was found in 2 of 14 synovial fluid specimens; however, in the vast majority the levels were so low that detection proved elusive (30).…”

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confidence: 99%

Failure To Detect Muramic Acid in Normal Rat Tissues but Detection in Cerebrospinal Fluids from Patients with Pneumococcal Meningitis

et al. 2000

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Muramic acid serves as a marker for the presence of bacterial cell wall debris in mammalian tissues. There have been a number of controversial and sometimes conflicting results on assessing the levels of muramic acid in health and disease. The present report is the first to use the state-of-the art technique, gas chromatographytandem mass spectrometry, to identify and quantify the levels of muramic acid in tissues. Muramic acid was not found in normal rat brain or spleen. However, when tissues were spiked with muramic acid, it was readily identified. The detection limit was <1 ng of muramic acid/100 mg (wet weight) of tissue. The levels of muramic acid reported in diseased human spleen and spleen of arthritic rats, previously injected with bacterial cell walls, were 100-to 1,000-fold higher. In the present study, muramic acid was also readily detected in the cerebrospinal fluid of patients with pneumococcal meningitis (6.8 to 3,900 ng of muramic acid/ml of cerebrospinal fluid). In summary, there can be an enormous difference in the levels of muramic acid found in different mammalian tissues and body fluids in health and disease. This report could have great impact in future studies assessing the role of bacterial cell wall remnants in the pathogenesis of certain human inflammatory diseases.

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“…Mur is readily demonstrated in body fluids in documented infection, including septic arthritis (7,14,27), bacterial meningitis (23), and urinary tract infections (2). It has also been reported that Mur is detectable in reactive arthritis.…”

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confidence: 98%

Muramic Acid Is Not Generally Present in the Human Spleen as Determined by Gas Chromatography-Tandem Mass Spectrometry

2002

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It has been hypothesized that bacterial debris may accumulate in tissues of the reticuloendothelial system (RES) serving as an inflammatory stimulus for human disease. In support of this hypothesis, muramic acid (Mur), a component of bacterial peptidoglycan (PG), has previously been reported to be present in culturenegative human spleen. High-performance liquid chromatography (HPLC) was employed in these analyses, and a peak was detected at the retention time of Mur. However, HPLC is best used as a screening technique, and it is vital that these tentative observations be reexamined by the state-of-the-art approach (gas chromatography-tandem mass spectrometry [GC-MS 2 ]). Indeed, in the present work using GC-MS 2 , Mur was not detected in six out of seven human spleens previously examined by HPLC. However, Mur was categorically detected at minute concentrations, 50 ppb, in one spleen. In conclusion, since Mur is not generally found in culture-negative human spleen, in future studies, these tissues can serve as negative controls. The study of Mur levels in inflammation (e.g., reactive arthritis) could prove important in testing the hypothesis that bacterial debris persisting in tissues could serve as a depot inciting diseases of unknown etiology.

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Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids

Cited by 30 publications

References 14 publications

A Urinary Marker for Occult Systemic Coccal Disease

A Urinary Marker for Occult Systemic Coccal Disease

Failure To Detect Muramic Acid in Normal Rat Tissues but Detection in Cerebrospinal Fluids from Patients with Pneumococcal Meningitis

Muramic Acid Is Not Generally Present in the Human Spleen as Determined by Gas Chromatography-Tandem Mass Spectrometry

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