Modification of the Staphylococcus aureus fibronectin binding phenotype by V8 protease

The amount of cell surface fibronectin (Fn)-binding protein (FnBP) adhesin expressed by Staphylococcus aureus is maximal during exponential growth but disappears rapidly as the culture progresses into stationary phase. To identify factors responsible for the loss of cell surface FnBP, a culture of S. aureus L170, which shows high levels of Fn binding, was supplemented at the time of inoculation with concentrated stationary-phase supernatant from S. aureus L530, a strain which binds Fn poorly. The resulting exponential-phase cells were devoid of FnBP. The factor responsible for this activity was purified from the culture supernatant and identified as V8 protease. When cultured with 375 ng of exogenous V8 protease ml(-1), exponential-phase cells of S. aureus L170 were devoid of cell surface FnBP, and concentrations as low as 23 ng x ml(-1) resulted in reduced amounts of FnBP. Addition of the protease inhibitor alpha2-macroglobulin to the culture medium prevented the growth-phase-dependent loss of cell surface FnBP, whereas growth with exogenous V8 protease resulted in reduced adherence to the solid-phase N-terminal fragment of Fn and to the extracellular matrix synthesized by fetal rabbit lung fibroblasts. Although FnBP was extremely sensitive to V8 protease, exogenous protease did not exert a significant influence on the amount of cell surface protein A. However, a limited number of other high-molecular-weight cell surface proteins were also sensitive to V8 protease. Therefore, both the adhesive phenotype and cell surface protein profile of S. aureus can be modified by V8 protease activity.     

Clumping of Staphylococcus aureus by human fibronectin

Clumping of different staphylococci by fibronectin and other purified plasma proteins has been investigated. Purified fibronectin was capable of clumping Staphylococcus aureus strains in concentrations identical with concentrations of fibronectin in human plasma. S. epidermidis and S saprophyticus were not clumped by fibronectin. The binding of fibronectin to S. aureus was not mediated by protein-A, as a strain lacking protein-A clumped in the presence of fibronectin, and the presence of IgG could not inhibit the clumping of S. aureus strains. The fibronectin-binding component on the staphylococcal cell wall seems to be unrelated to the fibrinogen-binding clumping factor.     

Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users

Right-sided endocarditis caused by Staphylococcus aureus is a frequent complication of injection drug use. Fortunately, the prognosis for this infection when treated with the standard regimen of 4 to 6 weeks of parenteral antistaphylococcal antibiotics is favorable. Nevertheless, in many cases, once drug users feel better, they leave the hospital against medical advice before completing the full course of antibiotic therapy. This problem has stimulated interest in shortening the duration of antibiotic to a penicillinase-resistant penicillin. Data from in vitro synergy studies and animal models of endocarditis suggest that S. aureus can be eradicated more quickly by combination therapy than by monotherapy. Reports of three prospective, nonrandomized clinical trials have been published that support the use of a 2-week course of a penicillinase-resistant penicillin and an aminoglycoside antibiotic to treat uncomplicated, exclusively right-sided endocarditis caused by methicillin-susceptible S. aureus in injection drug users.     

Postoperative enteritis caused by methicillin-resistant Staphylococcus aureus

We examined the clinical features of 14 men (mean age 72 years) with postoperative enteritis caused by methicillin-resistant Staphylococcus aureus (MRSA). The patients had all undergone surgery for the treatment of digestive diseases and had received antibiotic prophylaxis consisting of an extended-spectrum cephem. Diarrhea appeared a mean of 3.3 days postoperatively and lasted for 5 days on average. In severe cases organ insufficiency was involved. Coagulate-positive staphylococci were the predominant organisms isolated from watery diarrhea. In 13 of 14 patients, coagulase type II isolates producing enterotoxins A, C and toxic shock syndrome toxin-1 (TSST-1) with enterotoxin A, C, and 1st genes were isolated. These strains were sensitive to vancomycin and arbekacin; however, they were highly resistant to many other antibiotics. We also investigated the effects of a glucocorticoid hormone and gamma globulin on production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) obtained from healthy volunteers. TNF-alpha and IL-2 production was enhanced by TSST-1 and the supernatant of Iscove-modified dulbecco medium, in which coagulase type II isolates producing enterotoxins A, C and TSST-1 with enterotoxin A, C were cultured for 24 h. Both glucocorticoid hormone and gamma globulin suppressed TNF-alpha and IL-2 production, thus suggesting that these drugs may be effective in treating postoperative MRSA enteritis.     

Characteristics and treatment of Staphylococcus aureus endocarditis

In order to evaluate whether there were changes of the clinical features of Staphylococcus (Staph.) aureus endocarditis in recent years, the data of 21 cases of Staph. aureus endocarditis diagnosed from 1977 to 1994 were analyzed and compared with those of 11 cases of Staph. aureus endocarditis from 1957 to 1977. The results showed the following changes in recent years. The incidence of Staph. aureus endocarditis cases has been increasing. Cases of right-sided endocarditis increased in the recent two decades and this increase was related to intravenous drug abuse and increased use of vascular intervention. Right-sided endocarditis was different from left-sided endocarditis in their risk factors, underlying heart diseases, clinical manifestations and prognosis. The clinical manifestations of ventricular-wall endocarditis were atypical and it could be definitely diagnosed only with echocardiogram. Complications of Staph. aureus endocarditis became more common and serious, in recent decades but hospital mortality decreased markedly due to effective antibiotic management. The authors believe that sound knowledge of Staph. aureus endocarditis is essential for the proper diagnosis and treatment of Staph. aureus endocarditis.     

Fatal Staphylococcus aureus infective endocarditis: the dental implications

Rates of infant mortality and prematurity or low birthweight serve as indirect measures of the health of a nation. This paper presents current population data documenting the still serious problem of perinatal outcome in the USA as well as in other economically developed countries. International comparisons suggest that nations which have the greatest inequality of income and social opportunity also have the most adverse perinatal, child and adult health outcomes. Furthermore, the data assert that these effects are independent of average national wealth or gross national economic productivity. Health status differs by social class and race, even among the most affluent sectors of the population. All social classes, even the wealthiest, suffer the health consequences of social inequalities. An explanatory socio-psychological theory of causality is proposed.     

Spondylitis and medullary transverse syndrome caused by Staphylococcus aureus

Three cases of haematogenous osteomyelitis in the vertebral column caused by Staphylococcus aureus are reported. The cases, which were associated with severe neurological symptoms and/or death, were initially characterized by a long period with no or discrete local signs of infection and by values of temperature and leucocyte counts within or close to normal values. In this period measurements of the sedimentation reaction and C-reactive protein were elevated, and were markers of persistent infection. At the Department of Clinical Microbiology in the county of Copenhagen blood cultures from a total of 49 patients were found to be positive for S. aureus during the period January to March 1996. Six patients were found to have osteomyelitis (12%, including four cases of spondylitis) and nine patients were suspected of having osteomyelitis. This frequency of patients with S. aureus bacteraemia having osteomyelitis was significantly higher than reported in another Danish study (10), which together with the severe outcome of the infection emphasizes the need for attentiveness to these serious complications of S. aureus bacteraemia.     

Staphylococcus aureus binding to human nasal mucin

Colonization of human nasal mucosa with Staphylococcus aureus sets the stage for subsequent systemic infection. This study characterizes S. aureus adhesion to nasal mucosa in vitro and investigates the interaction of S. aureus with human nasal mucin. S. aureus binding to cell-associated and cell-free mucus was greater than to nonmucin-coated epithelial cells. Scanning electron microscopy of S. aureus incubated with human nasal mucosal tissue showed minimal binding to ciliated respiratory epithelium. In a solid-phase assay, S. aureus bound to purified human nasal mucin-coated wells significantly more than to bovine serum albumin-coated microtiter wells. Binding to mucin was saturable in a dose- and time-dependent fashion. Staphylococcal adherence to human nasal mucin was inhibited by bovine submaxillary mucin but not by fibrinogen. Pretreatment of mucin with periodate but not with pronase reduced adherence. Trypsin treatment of the bacteria significantly reduced adherence to mucin. 125I-labelled nasal mucin bound to two surface proteins (138 and 127 kDa) of lysostaphin-solubilized S. aureus. Binding to human nasal mucin occurs in part via specific adhesin-receptor interactions involving bacterial proteins and the carbohydrate moiety in mucin. These experiments suggest that S. aureus binding to mucin may be critical for colonization of the nasopharyngeal mucosa.     

Staphylococcus aureus bacteremia and endocarditis. New diagnostic and therapeutic concepts

The Health Care Financing Administration (HCFA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducted a demonstration between 1982 and 1985 to test the feasibility of providing payments for alcoholism treatment services to Medicare and Medicaid recipients in specially selected freestanding facilities. This study of the Medicare part of the demonstration answers two questions: do freestanding facilities save money for Medicare and do their patients have lower health care utilization following initiation of treatment than patients treated in hospital-based facilities? The statistical methodology is a logit and cluster approach. The analysis begins with a logistic regression model to predict the probability of patients seeking alcoholism treatment in either the demonstration (freestanding facility) or hospital-based cohort. The statistically significant variables from logit analysis are then used to form clusters. The health expenditures of freestanding and hospital patients are compared within homogeneous clusters. This study shows that the number of admissions, the average length of stay, and the average monthly health expenditures following the start of treatment are lower for the group treated in the freestanding facilities. The conclusion is that for some persons with alcohol problems, treatment in freestanding facilities is less costly and leads to lower subsequent health care utilization than treatment in hospitals.     

Some biochemical properties of the components of Staphylococcus aureus binding to human platelets

The purpose of this study was to ascertain whether pulmonary function in children who were lifetime residents of the highly polluted district of Teplice in northern Bohemia was lower than that for children who were lifetime residents of the cleaner district of Prachatice in southern Bohemia. Forced expiratory spirometry was measured twice (February/March and April) in approximately 235 eighth-grade students in each district. On both testing occasions, height-adjusted forced expiratory volume in 1 s and forced expiratory flow between 25% and 75% forced vital capacity were significantly lower (p < .001) in children from Teplice than in those from Prachatice. These differences were not associated with parental smoking habits, presence of pets, heating/cooking fuels, private home/apartment residency, or rural/urban residency. In Teplice, no differences were observed between lung functions measured at the end of the high pollution season (February/March) and those measured after the children breathed much cleaner air for a 4-wk period (April). This result was suggestive of a condition of chronically depressed lung function. No differences across times were observed in Prachatice, indicating that our measurements were reliable.     

Impact of the high-affinity proline permease gene (putP) on the virulence of Staphylococcus aureus in experimental endocarditis

Staphylococcus aureus causes a wide variety of invasive human infections. However, delineation of the genes which are essential for the in vivo survival of this pathogen has not been accomplished to date. Using signature tag mutagenesis techniques and large mutant pool screens, previous investigators identified several major gene classes as candidate essential gene loci for in vivo survival; these include genes for amino acid transporters, oligopeptide transporters, and lantibiotic synthesis (W. R. Schwan, S. N. Coulter, E. Y. W. Ng, M. H. Langhorne, H. D. Ritchie, L. L. Brody, S. Westbrock-Wadman, A. S. Bayer, K. R. Folger, and C. K. Stover, Infect. Immun. 66:567-572, 1998). In this study, we directly compared the virulence of four such isogenic signature tag mutants with that of the parental strain (RN6390) by using a prototypical model of invasive S. aureus infection, experimental endocarditis (IE). The oligonucleotide signature tag (OST) mutant with insertional inactivation of the gene (putP) which encodes the high-affinity transporter for proline uptake exhibited significantly reduced virulence in the IE model across three challenge inocula (10(4) to 10(6) CFU) in terms of achievable intravegetation densities (P, <0.05). The negative impact of putP inactivation on in vivo survival in the IE model was confirmed by simultaneous challenge with the original putP mutant and the parental strain as well as by challenge with a putP mutant in which this genetic inactivation was transduced into a distinct parental strain (S6C). In contrast, inactivation of loci encoding an oligopeptide transporter, a purine repressor, and lantibiotic biosynthesis had no substantial impact on the capacity of OST mutants to survive within IE vegetations. Thus, genes encoding the uptake of essential amino acids may well represent novel targets for new drug development. These data also confirm the utility of the OST technique as an important screening methodology for identifying candidate genes as requisite loci for the in vivo survival of S. aureus.     

Inflammation in the bovine teat cistern induced by Staphylococcus aureus

The inflammatory response, characterized by the accumulation of leukocytes, bovine serum albumin and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase, was studied after inoculation of either 5 x 10(5) colony-forming units (CFU) or 2 x 10(2) CFU of the Staphylococcus aureus strain SA 14391 into teat cisterns of dry cows after surgical closure of the passage between the teat and udder cisterns. Teat cistern samples were taken before, and twice daily for 7 days after, inoculation of the bacteria. Infusion of sterile saline constituted a control. Persistent infections occurred in all teats inoculated with the higher dose (5 x 10(5) CFU) of bacteria, and a prominent inflammatory response was elicited. Marked differences were observed in leukocyte migration patterns between different cows, and a cyclic influx of leukocytes was evident. Inoculation of the lower dose (2 x 10(2) CFU) of bacteria did not result in a persistent infection, and only a slight inflammatory response was observed. The results indicate that the bovine teat tissues are capable of mounting a strong local inflammatory response to S. aureus infection. A large number of leukocytes invaded the teat, but, despite their numbers, they were unable to subdue the infection, except when the bacterial count was low.     

Occlusion of the common iliac artery caused by mycotic endocarditis

Mycotic endocarditis has an incidence of 6.7% of all the forms of endocarditis and in 33-75% of the cases it complicates with peripheral embolization, more frequently to the lower limbs. Although the prognosis of the mycotic endocarditis is improved in the last years, it remains particularly serious especially when it's associated with arterial peripheral embolization. The authors report their experience in the surgical treatment of one case of occlusion of the iliac artery secondary to mycotic endocarditis, making a review of the Literature on this matter.     

Absorption of various actinomycins by Staphylococcus aureus cells

The absorption of actinomycin D by the cell suspension of Staphylococcus aureus via diffusion linearly depended on the antibiotic concentration in the suspension within the ranges of 2 to 15 micrograms/ml. The absorption of active actinomycins C2, C3 and Au6 was the same as that of actinomycin D. The Staphylococcus intact membranes limited the inlet of the actinomycins to the cells since the membranotropic substances such as gramicidin S and its derivatives and thyrocidin increased their absorption by 30-70 per cent. The absorption of a low active actinomycin D0 and inactive actinomycinic acid even after the exposure to the membranotropic substances was not detectable. These compounds did not form any complexes with DNA. The level of the absorption of the actinomycins by the cells was likely defined by their ability to complex with DNA.