Protection of phagocytosed bacteria against antimicrobial agents.

Antibiotic sensitive Staphylococcus aureus phagocytosed by human neutrophil granulocytes were exposed to penicillin G (benzyl penicillin), gentamicin or rifampicin in concentrations from 2.5 U/ml, 2.5 microgram/ml and 0.2 microgram/ml to 250 U/ml, 250 microgram/ml and 20 microgram/ml, respectively. The bacteria were protected from the antibacterial effects of penicillin G and gentamicin. Considerable numbers of phagocytosed bacteria remained viable after 24 hours exposure to antibiotic concentrations that killed more than 99% of extracellular bacteria in less than one hour. Killing of intracellular bacteria was more pronounced with rifampicin, indicating that the penetration of this drug into the phagocytic vacuole is superior to penicillin G and gentamicin.     

Bactericidal activity of antituberculosis drugs against Mycobacterium avium complex

The bactericidal activity of antituberculosis drugs against two strains of M. avium complex 13008 (serotype 20) and 13016 (serotype 4), was observed using modified Dubos liquid medium (1.3 g of Dubos Broth Base (Difco) in 180 mil of distilled water plus 20 ml of bovine serum). The strains were most susceptible to antituberculosis drugs among M. avium complex strains (Table). The test strains were cultivated in Ogawa egg medium at 37 degrees C for 10 days, and growing colonies were homogenized by shaking with glass beads for 10 minutes and suspended in the modified Dubos liquid medium to a concentration of 2 mg wet weight per ml. The media containing drug and containing no drug were incubated at 37 degrees C for 24 hours under shaking (8 cm-moving range and 56 strokes per minute). After incubation, the medium was diluted by a 0.1% Tween 80 aqueous solution to 10(-7), and each 0.02 ml-sample of 10(-4) to 10(-7) suspensions was inoculated onto Ogawa egg medium. The Ogawa egg medium slants were incubated at 37 degrees C for 28 days, and the number of colonies was counted. The bactericidal activity was determined as a ratio of the number of colony-forming units in 10 ml-aliquot of drug-containing Dubos liquid medium against the number of colony-forming units in the control Dubos liquid medium. The results are shown in Figures 1 and 2. Under the condition tested, rifampicin, isoniazid, ethambutol, ethionamide and cycloserine did not exhibit any bactericidal activity, and only streptomycin and enviomycin exhibited bactericidal activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antimicrobial activity of Gynostemma pentaphyllum extracts against fungi producing aflatoxin and fumonisin and bacteria causing diarrheal disease

Gynostemma pentaphyllum was investigated to determine its antimicrobial activities against human.and animal pathogens that produce aflatoxin, fumonisin, and diarrheal disease. The fungi were Aspergillusflavus, Aspergillus parasiticus and Fusarium verticillioides. The bacteria were Vibrio, Salmonella, Shigella, Escherichia coli and Staphylococcus aureus. G. pentaphyllum was extracted by five different methods. The obtained extracts were designated Extracts A, B, C, D and E. The results of the antifungal assay against A.flavus andA. parasiticus showed Extracts A and B at 10,000 ppm inhibited growth at 8-28%. Extracts A and B at 10,000 ppm also showed activity against F. verticillioides at 41-43%. Extract A, B and C were able to inhibit the tested strains better than the Extracts D and E. The MIC values of the extracts against gram-negative bacteria ranged from 相似文献   

Bone infections involving anaerobic bacteria.

Over 700 cases of anaerobic osteomyelitis have been reported in the literature. Nonetheless, most reviews of osteomyelitis have paid little attention to the potential role of anaerobes in bone infections. There have, as yet, been no prospective studies of osteomyelitis utlizing optimal anaerobic transport and culture techniques. In a retrospective study of osteomyelitis at Wadsworth VA Hospital from 1973--1975, 39 percent of 58 patients with osteomyelitis had an infection involving anaerobes. Anaerobes were isolated from 81 percent of 27 patients whose specimens were cultured anaerobically. Anaerobes were isolated from nine of ten samples of bone. Anaerobic bacteria were part of a mixed flora involving facultative bacteria in all but two cases. All of the patients with anaerobic infection had non-hematogenous osteomyelitis. Non-hematogenous disease comprises 80--90 percent of the osteomyelitis seen in adults. Our experience at Wadsworth VA Hospital and a review of the literature lead us to believe that anaerobes play a much larger role in osteomyelitis than has been appreciated previously. Infections of the calvarium, mastoid, mandible, maxilla and the extremities are most likely to involve anaerobes. Predisposing conditions include paranasal sinusitis, otitis media, periodontal disease, trauma, peripheral vascular disease, peripheral neuropathy and/or chronic osteomyelitis. The presence of a foul odor is a valuable clinical clue to the presence of anaerobes. Bacteroides, fusobacteria and anaerobic cocci have been reported with almost equal frequency from anaerobic bone infections. While Bacteroides fragilis is the most common anaerobe isolated in infections of other organ systems, it does not appear to be a common pathogen in anaerobic bone infections. The role of anaerobes in osteomyelitis is not yet resolved. They have been isolated in pure culture from infected bone, and under those circumstances are clearly pathogenic. Anaerobes are found more frequently as part of a mixed flora with facultative streptococci, gram-negative bacilli, and less often with S. aureus. In this setting it is unclear which organism or organisms are the primary invaders, or whether there is a synergistic mechanism of infection. The reliability of sinus drainage cultures also remains to be determined. Our retrospective study suggests that certain anaerobes isolated from sinus drainage are not present in infected bone. Cultures of bone or an abscess adjacent to bone would be expected to give more reliable data. The majority of anaerobes other than B. fragilis are susceptible to levels of penicillin achievable with parenteral administration of the antibiotic. Anaerobic pathogens should be sought in the situations noted above. We feel that parenteral penicillin should be part of the initial antibiotic regimen in patients with suspected or documented anaerobic bone infection...     

Pleuropulmonary lung infection by anaerobic bacteria.

Two patients with severe pleuropulmonary infection caused by non-sporing anaerobic bacteria are described. One had an empyema with foul-smelling pus and developed bacteraemia, and the other developed a lung abscess. Both were successfully treated with antibiotics and drainage, chest surgery being avoided. The successful diagnosis and treatment of these patients involved close liaison between clinical and laboratory staff.     

Identification of simple arylfluorosulfates as potent agents against resistant bacteria

Sulfur fluoride exchange (SuFEx), a next generation of click chemistry, opens an avenue for drug discovery. We report here the discovery and structure–activity relationship studies of a series of arylfluorosulfates, synthesized via SuFEx, as antibacterial agents. Arylfluorosulfates 3, 81, and 101 showed potency to overcome multidrug resistance and were not susceptible to the generation of resistance. They exhibited rapid bactericidal potency and selectively killed gram-positive bacterial strains. These compounds also exhibited the ability to disrupt established bacterial biofilm and kill persisters derived from biofilm. Furthermore, arylfluorosulfate 3 had a synergistic effect with streptomycin and gentamicin. In addition, their anti-MRSA potency was evaluated and determined by the Caenorhabditis elegans model.

Antibiotic resistance is a tremendous threat to global health. Some of the most concerning multidrug-resistant pathogen strains include methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA, respectively), vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (1–3). Antibiotic resistance is one of the biggest public health challenges and is a leading cause of death with at least 2.8 million infected cases and more than 35,000 deaths every year in the United States (4). Therefore, the development of novel antibacterial drugs with the ability to overcome drug-resistance is urgently needed. Furthermore, our general understanding of the role of our microbiomes (i.e., skin, oral, gut, etc.) in antibiotic resistance and responses is ever increasing (5–7). The next generation of antibacterial agents will require limited drug promiscuity to eliminate resistance and decrease unwanted off-target effects on our symbiotic commensal organisms and immunity (8, 9).Sulfur fluoride exchange (SuFEx) (10), a new generation of click chemistry, has found diverse applications to chemical synthesis (11–16), materials science (17–22), chemical biology (23–28), and drug discovery (29, 30). In our previous studies, we demonstrated that SuFEx modification is a highly reliable approach for the late-stage functionalization of drugs and drug-like molecules to generate new compounds with improved properties (31, 32). Later on, Ravindar et al. reported the synthesis of arylfluorosulfate analogs and screened them for antimicrobial activity (33).Here we report further screening studies on arylfluorosulfate derivatives (Ar-O-SO₂-F) in our laboratory and have found several simple molecules which are potent against methicillin- and vancomycin-resistant strains (Fig. 1 and SI Appendix, Figs. S1 and S2). Through structure and activity relationship (SAR) studies, we determined that the -OSO₂F moiety is essential for these compounds’ antibacterial activities. Not only are they capable of inhibiting bacterial biofilm formation, but they are also able to disrupt established bacterial biofilm and induce the killing of persister cells. Significantly, these arylfluorosulfates are effective against MRSA infection in a Caenorhabditis elegans-based infection model. Our findings reported here thus may serve as the foundation toward the development of arylfluorosulfate-based antibacterial agents.Open in a separate windowFig. 1.(A) Arylfluorosulfates were derived from phenols or phenol’s precursors. (B) The structures of antibacterial arylfluorosulfates 3, 81, and 101 and their MIC values against MRSA.     

抗结核药物作用新靶点及其研究进展

结核病是威胁我国乃至全世界的健康问题。由于细菌变异、治疗方案不合理和药物滥用等原因导致细菌耐药情况越来越严重,耐药结核病已经威胁到了全人类的健康安全。近10年来针对结核分枝杆菌各种新靶点的抗结核新药已经陆续进入临床试验,作者对抗结核分枝杆菌研究中细胞壁合成、蛋白质合成和能量代谢机制的新靶点进行梳理和分析,并且对一些相关的新型化合物进行简要介绍,以期为抗结核药物的研发提供参考。     

In vitro susceptibility testing of anaerobic bacteria.

In vitro susceptibility testing of anaerobic bacteria should be limited to isolates from persistent or recurrent infections that have been treated adequately and appropriately with antimicrobial agents and, in reference centers, to collections of isolates in order to monitor alterations in susceptibility of species to various antimicrobial agents. An agar dilution reference method is being evaluated currently; however, practicality limits sporadic testing of single isolates to disk elution or broth dilution techniques. No single disk diffusion method has yet been found to be acceptable for testing anaerobic bacteria, and the results obtained with standardized procedures for aerobic and facultatively anaerobic bacteria are not applicable to anaerobic bacteria.     

Topics on anaerobic bacteria and anaerobic infection

Considerable information has been accumulated in the field of anaerobic bacteria and anaerobic infections in the last ten years. Here we tried to briefly introduce several selected topics of clinical importance in this field: Proposal of the term "Nanaerobe", Changes of classification and nomenclature of anaerobes, Anaerobic bacteremia, Lemierre's syndrome as a revival anaerobic infection, Atopobium vaginae as Bacterial Vaginosis-associated bacteria, and new actions of the Clostridium perfringens toxins.     

Antimicrobial activity of Lactobacillus against microbial flora of cervicovaginal infections

ObjectiveTo assess the probiotic nature of Lactobacillus in preventing cervical pathogens by studying the effectiveness of antimicrobial activity against vaginal pathogens.MethodsLactobacilli were isolated from healthy vaginal swabs on selective media and different pathogenic bacteria were isolated by using different selective media. The Lactobacillus strains were tested for the production of hydrogen peroxide and antimicrobial compounds along with probiotic properties.ResultsOf the 10 isolated Lactobacillus strains, strain 1, 3 and 6 are high hydrogen peroxide producers and the rest were low producers. Results of pH and amines tests indicated that pH increased with fishy odour in the vaginal fluids of cervicovaginal infection patients when compared with vaginal fluids of healthy persons. The isolates were found to be facultative anaerobic, Gram-positive, non-spore-forming, non-capsule forming and catalase-negative bacilli. The results of antimicrobial activity of compounds indicated that 280 and 140 μg/mL was the minimum concentration to inhibit the growth of both pathogens and test organisms respectively.ConclusionsThe results demonstrated that Lactobacillus producing antimicrobial compounds inhibits the growth of cervical pathogens, revealing that the hypothesis of preventing vaginal infection by administering probiotic organisms has a great appeal to patients, which colonize the vagina to help, restore and maintain healthy vagina.