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PubMed1981

Variable tolerance of a clinical isolate of Staphylococcus epidermidis from an infected hydrocephalus shunt for several beta-lactam antibiotics, vancomycin and fosfomycin.

A strain of Staphylococcus epidermidis isolated from an infected hydrocephalus shunt with associated ventriculitis in a 3-month-old infant proved variably tolerant for the beta-lactam antibiotics ampicillin, cephalothin, cefotaxime, cefoxitin, oxacillin, penicillin G, as well as vancomycin and fosfomycin. In contrast, Staphylococcus aureus control strain ATCC 25923 was regularly tolerant to the above stated beta-lactam antibiotics; however, this latter strain displayed variable tolerance for vancomycin and fosfomycin. The beta-lactam tolerance of both strains proved inoculum sizes. Penicillin G-tolerant variants were detected more readily among cells of the S. epidermidis strain in the stationary than in the logarithmic growth phase; in contrast, the yield of penicillin G-tolerant variants from S. aureus ATCC 25923 was independent of the growth phase. Tolerant variants of both staphylococcal strains failed to survive more than three successive passages in Mueller-Hinton broth with added beta-lactam antibiotics at concentrations identical to those which had originally served to select these tolerant variants. Gentamicin combined with vancomycin displayed additive bactericidal activity against both staphylococcal strains; conversely, the combination of rifampin plus vancomycin showed inadequate bactericidal activity against both strains.

Anti-Bacterial Agents↗

PubMed2003

A new topical model of Staphylococcus corneal infection in the mouse.

PURPOSE: To establish, in the scarified mouse eye, a new model of Staphylococcus aureus keratitis suitable for studies of pathogenesis and host defense mechanisms. METHODS: Corneas of three strains of mice (BALB/c, A/J, and C57BL/6) were scarified and inoculated with S. aureus strain 8325-4. Mice underwent slit lamp examination (SLE) at 1, 3, 5, 7, and 9 days after infection and were killed. Histopathologic analyses, determination of bacterial colony-forming units (CFU), and myeloperoxidase (MPO) activity assays were performed at each time point. RESULTS: S. aureus keratitis developed in both BALB/c and A/J strains of mice, but not in C57BL/6. The BALB/c and A/J strains demonstrated greater susceptibility to infection, as evidenced by significantly higher SLE scores and more viable bacteria per infected eye than in C57BL/6 mice at 5, 7, and 9 days after infection (P <or= 0.0001). Histopathologic analysis and MPO assays of infected A/J mice both revealed an influx of polymorphonuclear leukocytes (PMNs). Histology demonstrated presence of leukocytes in the aqueous humor, migration of PMNs into infected tissue, corneal erosion, and edema in the eyes of infected A/J mice. Whereas infected BALB/c mice demonstrated both PMN migration and corneal edema, eyes of infected C57BL/6 mice failed to show even mild histopathologic changes. CONCLUSIONS: These studies demonstrate the establishment of Staphylococcus keratitis in the mouse eye. This model should provide for a large range of future studies that are currently unavailable in the rabbit keratitis model, particularly those requiring a genetically altered host or specific immunologic reagents.

Animals↗

PubMedDate not supplied

Rupture of a nonaneurysmal aorta secondary to Staphylococcus aortitis.

Infectious aortitis has become increasingly uncommon and, when diagnosed, typically occurs in an immunocompromised elderly male with a history of Staphylococcus or Salmonella infection and underlying atheromatous cardiovascular disease. The authors report a case of a 74-year-old man with aortitis complicated by rupture secondary to Staphylococcus aureus infection. The patient presented with worsening abdominal pain and fever after being discharged from the emergency room 2 weeks before with back pain and leukocytosis diagnosed as urinary tract infection and bronchitis. Computed tomography (CT) imaging of the retroperitoneum on the first visit appeared normal. Repeat CT scan on the subsequent visit revealed a contained rupture of a nonaneurysmal aorta at the level of the diaphragm. The patient was taken to the operating room emergently for repair. An infected periaortic hematoma and a 1 cm perforation in the posterior aorta were found. The aorta was excised and the area debrided. Revascularization was performed using a 22 mm extruded polytetrafluoroethylene (ePTFE) interposition graft placed in situ. This case demonstrates that a high index of suspicion is required in diagnosing infectious aortitis and that the diagnosis may be delayed in many cases. Additionally, it may not be uncommon for the infected aorta to rupture without prior aneurysm formation.

Aged↗

PubMed1992

Community-acquired methicillin-resistant Staphylococcus aureus infections in otolaryngology.

Soon after the introduction of methicillin, strains of Staphylococcus aureus resistant to methicillin were reported. Methicillin-resistant Staphylococcus aureus (MRSA) has become a common hospital pathogen, often resistant to multiple antibiotics, while causing significant morbidity and mortality. Community-acquired MRSA infections have been infrequently documented. Most reports have been associated with intravenous drug abuse. This report reviews 15 patients with community-acquired MRSA infections of the head and neck. None admitted to intravenous drug use. Additionally, no patient was known to be a healthcare worker. The MRSA strains showed antibiotic susceptibility and resistance profiles different from typical hospital-acquired MRSA isolates. All but one infection resolved with adequate surgical or appropriate antibiotic therapy. Clinicians should become aware of the possibility of community-acquired MRSA in the patient who has had continued infection despite antibiotic therapy.

Abscess↗

PubMed2005

Clinical behavior of implant infections due to Staphylococcus epidermidis.

UNLABELLED: Surgical implants and other foreign material are increasingly used in modern medicine to restore or to improve the function of the human body. Infection of an implant is associated with considerable morbidity due to frequent hospitalizations, surgery and antimicrobial treatment. The underlying mechanism is the formation of a bacterial biofilm on the surface of the implanted body. The recognition and diagnosis of implant infections is essential for further therapy and, above all, the decision to remove and exchange the implant. METHODS: We compared the data of 60 patients with implant infections with those of 60 patients with transient bacteremia caused by Staphylococcus epidermidis. The pathogens isolated from blood were characterized with regard to antimicrobial susceptibility and formation of biofilms using a static microtiter plate model. Wild type skin isolates from non-hospitalized healthy volunteers served as control with regard to antimicrobial susceptibility and biofilm formation. RESULTS: Clinical signs and symptoms, underlying diseases and outcome were not different in either group. However, patients with implant infection had fever over a longer time (mean 12 days versus 3 days, respectively, p < 0.05) and more often positive blood cultures than patients with transient bacteremia (3.1 versus 1.2, p < 0.05). Thrombocytopenia was observed in patients with implant infections but not in patients with transient bacteremia (p < 0.05). Biofilms were formed in 86.4 % of the isolates in implant infection, in 88.8 % in transient bacteremia and in 76.9 % of the isolates from healthy volunteers (not significant). Multi-resistance to penicillin, oxacillin, erythromycin, clindamycin, ciprofloxacin and trimethoprim was more common in the hospital strains than in the wild type strains (75.6 % versus 48.7 %, p < 0.05). CONCLUSIONS: The clinical features of implant infections are indistinguishable from those of transient bacteremia. Persisting fever and multiple blood culture yielding the growth of skin flora bacteria are strong indicators for infection of implanted material. Biofilm formation and antimicrobial multi-resistance, as common in implant infection as in transient bacteremia, seem to be accessory factors in infections due to Staphylococcus epidermidis.

Adult↗

PubMed2004

Ultrasonically enhanced vancomycin activity against Staphylococcus epidermidis biofilms in vivo.

Infection of implanted medical devices by Gram-positive organisms such as Staphylococcus ssp. is a serious concern in the biomaterial community. In this research the application of low frequency ultrasound to enhance the activity of vancomycin against implanted Staphylococcus epidermidis biofilms was examined. Polyethylene disks covered with a biofilm of S. epidermidis were implanted subcutaneously in rabbits on both sides of their spine. The rabbits received systemic vancomycin for the duration of the experiment. Following 24 h of recovery, one disk was insonated for 24 or 48 h while the other was a control. Disks were removed and viable bacteria counted. At 24 h of insonation, there was no difference in viable counts between control and insonated biofilms, while at 48 h of insonation there were statistically fewer viable bacteria in the insonated biofilm. The S. epidermidis biofilms responded favorably to combinations of ultrasound and vancomycin, but longer treatment times are required for this Gram-positive organism than was observed previously for a Gram-negative species.

Animals↗

PubMed2002

Comparative in vitro activity of quinupristin/dalfopristin and seven other antimicrobials against methicillin-susceptible and methicillin-resistant nosocomial Staphylococcus aureus bloodstream isolates.

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.

Anti-Bacterial Agents↗

PubMed2005

Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam antibiotics against Staphylococcus aureus and Enterococci by FIC index and timed-kill curves.

The interactions of daptomycin with gentamicin and 5 beta-lactam agents were determined by checkerboard and timed-kill studies. Eighty isolates were tested by checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and VRE. Checkerboard results showed highest frequency of synergistic effects against VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a modest effect with most combinations against VRE and MRSA (5-20%); and indifference with daptomycin and most agents against MSSA (0-5%); except with daptomycin with oxacillin where 10-20% synergy was observed. Synergistic interaction was confirmed by time kill studies in seven of ten isolates where checkerboard suggested synergy. A bactericidal effect was exerted in 5/7 synergistic combinations. The in vitro data suggest that daptomycin combined with other antibiotics may be microbiologically beneficial and not antagonistic.

Anti-Bacterial Agents↗

PubMed2006

Methicillin-resistant Staphylococcus aureus prevalence: current susceptibility patterns in Trinidad.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most widespread causes of nosocomial infections worldwide. Recently, reports have emerged that S. aureus strains recovered from community-acquired infections are also methicillin-resistant. This study was undertaken to analyze the prevalence of methicillin resistance among isolates at a regional hospital in Trinidad, and document the current resistance profile of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) to the commonly used anti-staphylococcal agents. METHODS: Over a 6-year period we analyzed 2430 isolates of S. aureus strains recovered from various clinical sources, from hospital and community practices. Antimicrobial susceptibility testing was done according to guideline recommendations of the National Committee for Clinical Laboratory Standards. RESULTS: The prevalence of MRSA from surgical/burn wounds, urine and pus/abscess were 60.1%, 15.5% and 6.6%, respectively. The major sources of MSSA were surgical/burn wounds, pus/abscess and upper respiratory tract specimens with rates of 32.9%, 17.1% and 14.3%, respectively. The greatest prevalence of resistance of MRSA was seen for erythromycin (86.7%), and clindamycin (75.3%). Resistance rates among MSSA were highest for ampicillin (70%). Resistance rates for tetracycline were similar among both MRSA (78.7%) and MSSA (73.5%). The MRSA recovery rates from nosocomial sources (20.8%) was significantly higher than that of previous years (12.5%) (p < 0.001), whereas rates among community isolates were relatively similar for the same period (4.1% versus 8.1%). CONCLUSION: The prevalence of MRSA in the hospital increased from 12.5% in 1999 to 20.8% in 2004. Most isolates were associated with infected surgical/burn wounds which may have become infected via the hands of HCPs during dressing exercises. Infection control measures aimed at the proper hand hygiene procedures may interrupt the spread of MRSA. HCPs may also be carriers of MRSA in their anterior nares. Surveillance cultures of both patients and HCPs may help to identify carriers who would be offered antibiotics to eradicate the organisms. Most MRSA are resistant to several non-beta-lactam antibiotics. Frequent monitoring of susceptibility patterns of MRSA and the formulation of a definite antibiotic policy maybe helpful in decreasing the incidence of MRSA infection.

Ampicillin↗

PubMed2005

Screening of crude extracts of six medicinal plants used in South-West Nigerian unorthodox medicine for anti-methicillin resistant Staphylococcus aureus activity.

BACKGROUND: Six Nigerian medicinal plants Terminalia avicennioides, Phylantus discoideus, Bridella ferruginea, Ageratum conyzoides, Ocimum gratissimum and Acalypha wilkesiana used by traditional medical practitioners for the treatment of several ailments of microbial and non-microbial origins were investigated for in vitro anti-methicillin Resistant Staphylococcus aureus (MRSA) activity. METHODS: Fresh plant materials were collected from the users. Water and ethanol extracts of the shredded plants were obtained by standard methods. The Bacterial cultures used were strains of MRSA isolated from patients. MRSA was determined by the reference broth microdilution methods using the established National Committee for Clinical Laboratory Standards break points. Staphylococcus aureus NCIB 8588 was used as a standard strain. Susceptibility testing and phytochemical screening of the plant extracts were performed by standard procedures. Controls were maintained for each test batch. RESULTS: Both water and ethanol extracts of T. avicennioides, P. discoideus, O. gratissimum, and A. wilkesiana were effective on MRSA. The Minimum Inhibition Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the ethanol extracts of these plants range from 18.2 to 24.0 mcg/ml and 30.4 to 37.0 mcg/ml respectively. In contrast, MIC range of 30.6 to 43.0 mcg/ml and 55.4 to 71.0 mcg/ml were recorded for ethanol and water extracts of B. ferruginea, and A. conyzoides respectively. Higher MBC values were obtained for the two plants. These concentrations were too high to be considered active in this study. All the four active plants contained at least trace amount of anthraquinones. CONCLUSION: Our results offer a scientific basis for the traditional use of water and ethanol extracts of A. wilkesiana, O. gratissimum, T. avicennioides and P. discoideus against MRSA-associated diseases. However, B. ferruginea and A. conyzoides were ineffective in vitro in this study; we therefore suggest the immediate stoppage of their traditional use against MRSA-associated diseases in Lagos, Nigeria.

Ageratum↗

PubMed2006

Prevalence and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus isolates from Trinidad & Tobago.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly prevalent worldwide since it was first reported in a British hospital. The prevalence however, varies markedly in hospitals in the same country, and from one country to another. We therefore sought to document comprehensively the prevalence and antimicrobial susceptibility pattern of MRSA isolates in Trinidad and Tobago. METHODS: All Staphylococcus aureus isolates encountered in routine clinical specimens received at major hospitals in the country between 2000 and 2001 were identified morphologically and biochemically by standard laboratory procedures including latex agglutination test (Staphaurex Plus; Murex Diagnostics Ltd; Dartford, England); tube coagulase test with rabbit plasma (Becton, Dickinson & Co; Sparks, MD, USA), and DNase test using DNase agar (Oxoid Ltd; Basingstoke, Hampshire, England). MRSA screening was performed using Mueller-Hinton agar containing 6 mug oxacillin and 4% NaCl, latex agglutination test (Denka Seiken Co. Ltd, Tokyo, Japan) and E-test system (AB Biodisk, Solna, Sweden). Susceptibility to antimicrobial agents was determined by the modified Kirby Bauer disc diffusion method while methicillin MICs were determined with E-test system. RESULTS: Of 1,912 S. aureus isolates received, 12.8% were methicillin (oxacillin) resistant. Majority of the isolates were recovered from wound swabs (86.9%) and the least in urine (0.4%) specimens. Highest number of isolates was encountered in the surgical (62.3%) and the least from obstetrics and gynaecology (1.6%) facilities respectively. Large proportions of methicillin sensitive isolates are >85% sensitive to commonly used and available antimicrobials in the country. All MRSA isolates were resistant to ceftriaxone, erythromycin, gentamicin and penicillin but were 100% sensitive to vancomycin, rifampin and chloramphenicol. CONCLUSION: There is a progressive increase in MRSA prevalence in the country but the present rate is still low in comparison to values in some other countries. Vancomycin is still the drug of choice for treating multidrug resistant MRSA infections. Further use of molecular studies to monitor the epidemiology of MRSA in these hospitals in the country is highly recommended too.

Humans↗

PubMed2006

Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia.

INTRODUCTION: To gain a better understanding of the clinical and economic outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in patients with early onset ventilator-associated pneumonia (VAP), we retrospectively analyzed a multihospital US database to identify patients with VAP over a 24 month period (2002-2003). METHOD: Data recorded included physiologic, laboratory, culture, and other clinical variables from 59 institutions. VAP was defined as new positive respiratory culture after at least 24 hours of mechanical ventilation (MV) and the presence of primary or secondary ICD-9-CM diagnosis codes of pneumonia. Outcomes measures included in-hospital morbidity and mortality for the population overall and after onset of VAP (duration of MV, intensive care unit [ICU] stay, in-hospital stay, and case mix and severity-adjusted operating cost). The overall cost was calculated at the hospital level using the Center for Medicare and Medicaid Services Cost/Charge Index for each calendar year. RESULTS: A total of 499 patients were identified as having VAP. S. aureus was the leading organism (31% of isolates). Patients with MRSA were significantly older than patients with methicillin-sensitive Staphylococcus aureus (MSSA; median age 74 versus 67 years, P < 0.05) and more likely to be medical patients. Compared with MSSA patients, MRSA patients on average consumed excess resources of 4.4 (95% confidence interval 0.6-8.2) overall MV days, 3.8 (-0.5 to +8.0) days of inpatient length of stay (LOS), 5.3 (1.0-9.7) ICU days, and US7731 dollars (-US8393 dollars to +US23,856 dollars) total cost after controlling for case mix and other factors. Furthermore, MRSA patients needed excess resources after the onset of VAP (4.5 [95% confidence interval 1.0-8.1] MV days, 3.7 [-0.5 to +8.0] inpatient days, and 4.4 [0.4-8.4] ICU days) after controlling for the same case mix and admission severity covariates. CONCLUSION: S. aureus remains a common cause of VAP. VAP due to MRSA was associated with increased overall LOS, ICU LOS, and attributable ICU LOS compared with MSSA-related VAP. Although not statistically significant because of small sample size and large variation, the attributable excess costs of MRSA amounted to approximately US8000 dollars per case after controlling for case mix and severity.

Aged↗

PubMed2025

Fingolimod as a potent anti-Staphylococcus aureus: pH-dependent cell envelope damage and eradication of biofilms/persisters.

BACKGROUND: The urgent need for new antibacterial drugs has driven interest in repurposing therapies to combat Gram-positive biofilms and persisters. Fingolimod, an Food and Drug Administration (FDA)-approved drug for multiple sclerosis, shows bactericidal activity, particularly against Methicillin-resistant Staphylococcus aureus (MRSA) and biofilm-related infections. With a well-documented safety profile and strong translational potential, it aligns with World Health Organization's goals for antimicrobial repurposing. However, the action mode and mechanism of Fingolimod against gram-positive bacteria remain elusive. METHODS: This study utilized clinical Staphylococcus aureus (S. aureus), Enterococcus faecalis (E. faecalis), Streptococcus agalactiae (S. agalactiae). And their susceptibility to Fingolimod and other antibiotics was tested via Minimum Inhibitory Concentration (MIC) assays. Biofilm inhibition and hemolytic activity were evaluated using crystal violet staining, Confocal Laser Scanning Microscopy (CLSM), and hemolysis assays, respectively, while the effect of phospholipids on Fingolimod efficacy was assessed with checkerboard assays. Membrane permeability and integrity were measured using SYTOX green staining and transmission electron microscopy. Whole-genome sequencing was performed on Fingolimod-resistant S. aureus isolates to identify Single Nucleotide Polymorphisms (SNPs) linked to resistance. RESULTS: Our data indicated that Fingolimod exerted bactericidal activity against a wide spectrum of gram-positive bacteria, including S. aureus, E. faecalis, S. agalactiae. Moreover, Fingolimod could significantly eliminate the persisters, inhibit biofilm formation and eradicate in-vitro mature biofilms of S. aureus. The mechanism by which Fingolimod rapidly eradicated S. aureus involved a pH-dependent disruption of bacterial cell permeability and envelope integrity. Concomitantly, exogenous supplementation of phospholipids in the culture medium resulted in a dose-dependent increase in the MIC of Fingolimod. Specifically, the addition of 64 μg/mL of cardiolipin (CL) and phosphatidylethanolamine (PE) completely nullified the bactericidal activity of Fingolimod at a concentration of 4 times the MIC. After four months of Fingolimod exposure, the MIC values of S. aureus showed a slight increase, indicating that it is not prone to developing drug resistance. CONCLUSION: Fingolimod exhibits bactericidal activity against diverse gram-positive bacteria, with remarkable effects on S. aureus (including MRSA), disrupting bacterial cell structural integrity in a pH-dependent way and eradicating biofilms and persisters of S. aureus.

Biofilms↗

PubMed2003

Ropivacaine 0.1% with sufentanil 1 microg/mL inhibits in vitro growth of Pseudomonas aeruginosa and does not promote multiplication of Staphylococcus aureus.

UNLABELLED: We investigated the effect of ropivacaine combined with sufentanil, a mixture frequently used for postoperative epidural analgesia, on the growth of Staphylococcus aureus and Pseudomonas aeruginosa at room temperature. Aliquots of suspension of S. aureus and P. aeruginosa in saline were transferred into test tubes containing either a mixture of ropivacaine 0.1% and sufentanil 1 microg/mL (R+S) or saline (SA), with the latter serving as control. At 0, 3, 6, 24, and 48 h after inoculation, 1 mL of each solution was spread over standard blood agar. The plates were incubated at 22 degrees C for 48 h, and the numbers of colony-forming units (cfu) were counted. The growth ratio for both bacterial strains was calculated as cfu time (t(n))/cfu baseline (t(0)). The primary efficacy variable was the area under the curve (AUC) in (cfu t(n)/cfu t(0)) x time, based on the growth ratios. The AUC for P. aeruginosa was significantly less in R+S than in SA (P = 0.028). Multiplication of P. aeruginosa (growth ratio >1) was observed for at least 6 h after inoculation in SA. Growth of P. aeruginosa was significantly less in R+S than in SA at 3 h (P = 0.043) and 24 h (P = 0.012) after inoculation. The AUC for S. aureus did not differ significantly between R+S and SA (P = 0.74). Neither R+S nor SA promoted multiplication of S. aureus. Forty-eight hours after inoculation, growth of S. aureus was significantly less in R+S than in SA (P < 0.0001). We conclude that R+S inhibited growth of P. aeruginosa and did not promote multiplication of S. aureus when compared with SA. IMPLICATIONS: This laboratory study demonstrated that compared with saline, ropivacaine 0.1% with 1 microg/mL of sufentanil inhibited growth of Pseudomonas aeruginosa and did not promote multiplication of Staphylococcus aureus at room temperature. With respect to bacterial infection with these two strains, the mixture seems to be safe for continuous epidural administration if prepared under aseptic conditions and after alcohol hand rub.

Amides↗

PubMed1986

Staphylococcus epidermidis ventriculitis treated with vancomycin and rifampin.

Two cases of ventriculitis with Staphylococcus epidermidis that failed on therapy with an antistaphylococcal penicillin are presented. Both infections responded to a combination of intravenous and intraventricular vancomycin and rifampin. Vancomycin and rifampin represent an important antibiotic regimen for the management of resistant infections of the central nervous system, especially with those due to S. epidermidis or methicillin-resistant Staphylococcus aureus.

Anti-Bacterial Agents↗

PubMed2004

Antimicrobial activity of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus.

The objective of this study was to investigate the antimicrobial activities of saturated fatty acids and fatty amines against methicillin-resistant Staphylococcus aureus (MRSA). The antimicrobial activity of saturated fatty acids and fatty amines was determined by oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96). Lauric acid, the most effective among the saturated fatty acids, showed antimicrobial activity at 400 microg/ml against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA. The minimal inhibitory concentration (MIC) of fatty amines depended on each hydrophobic chain length. The MIC of myristylamine was 1.56 microg/ml; most effective of the fatty amines. In time-kill curves, lauric acid and myristylamine produced a bactericidal effect and a bacteriostatic effect at 4-fold the MIC, respectively. The antimicrobial activities of lauric acid and myristylamine were decreased by human plasma. Cytotoxicity of 3 saturated fatty acids and 3 fatty amines was examined in cultured endothelial cells. Although cytotoxicity of fatty amines was severer than that of saturated fatty acids, myristylamine showed the highest value of apparent therapeutic index among them. DOX-96 was useful for screening antimicrobial substances, especially in the case of insoluble substances. We found that myristylamine showed anti-MRSA activity comparable to that of vancomycin and teicoplanin.

Amines↗

PubMed1999

Phenolic constituents of Cassia seeds and antibacterial effect of some naphthalenes and anthraquinones on methicillin-resistant Staphylococcus aureus.

Thirteen phenolic glycosides including six new compounds were isolated from seeds of Cassia tora (Leguminosae). The structures of the new compounds, rubrofusarin triglucoside (7), nor-rubrofusarin gentiobioside (9), demethylflavasperone gentiobioside (10), torachrysone gentiobioside (11), torachrysone tetraglucoside (12) and torachrysone apioglucoside (13), were elucidated on the basis of spectroscopic and chemical evidence. The effects of the phenolic glycosides, their aglycones and several other compounds structurally related to them on Escherichia coli K12, Pseudomonas aeruginosa PAO1 and some strains of Staphylococcus aureus were then examined. Among them, torachrysone (15), toralactone (16), aloe-emodin (18), rhein (19) and emodin (20) showed noticeable antibacterial effects on four strains of methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 2-64 micrograms/ml. On the other hand, the phenolic compounds tested did not show strong antibacterial effects on E. coli and P. aeruginosa.

Anthraquinones↗

PubMed2005

A novel type of immunity protein, NukH, for the lantibiotic nukacin ISK-1 produced by Staphylococcus warneri ISK-1.

Staphylococcus warneri ISK-1 produces a lantibiotic, nukacin ISK-1. The nukacin ISK-1 gene cluster consists of at least six genes, nukA, -M, -T, -F, -E, and -G, and two open reading frames, ORF1 and ORF7 (designated nukH). Sequence comparisons suggested that NukF, -E, -G, and -H contribute to immunity to nukacin ISK-1. We investigated the immunity levels of recombinant Lactococcus lactis expressing nukFEG and nukH against nukacin ISK-1. The co-expression of nukFEG and nukH resulted in a high degree of immunity. The expression of either nukFEG or nukH conferred partial immunity against nukacin ISK-1. These results suggest that NukH contributes cooperatively to self-protection with NukFEG. The nukacin ISK-1 immunity system might function against another lantibiotic, lacticin 481. Western blot analysis showed that NukH expressed in Staphylococcus carnosus was localized in the membrane. Peptide release/bind assays indicated that the recombinant L. lactis expressing nukH interacted with nukacin ISK-1 and lacticin 481 but not with nisin A. These findings suggest that NukH contributes cooperatively to host immunity as a novel type of lantibiotic-binding immunity protein with NukFEG.

Bacterial Proteins↗