Baicalein suppresses the SOS response system of Staphylococcus aureus induced by ciprofloxacin

Numerous antibiotics can induce an SOS repair system in bacteria that leads to antibiotic-resistant mutation of the bacterium. Therefore, searching for drugs that can prevent the SOS response and thus improve the long-term viability of some antibiotics is important. In this study, we aimed to detect the suppressive effects of baicalein on the SOS system and rifampin-resistant mutation in Staphylococcus aureus. We determined the reactive oxygen species (ROS) formation and intracellular ATP level in S. aureus with baicalein treatment to investigate the mechanisms involved in its effects on the SOS system. The results showed that baicalein was a potent inhibitor of the expression of the SOS genes RecA, LexA and SACOL1400. The rifampin-resistant mutation rate of S. aureus induced by ciprofloxacin was significantly reduced after treatment with baicalein. Treatment with baicalein led to a significant decrease in intracellular reactive oxygen species (ROS) formation and ATP level. Our findings indicate that baicalein may be an SOS-response inhibitor in S. aureus through inhibiting ROS formation and ATP production and may be used to prevent excessive mutation induced by antibiotics.     

氯氰碘柳胺与环丙沙星对耐甲氧西林金黄色葡萄球菌的体外联合药敏试验分析

目的 评价氯氰碘柳胺与环丙沙星联用对60株环丙沙星均为耐药的耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌效应.方法 采用棋盘法设计,微量肉汤稀释法测定不同浓度组合的抗菌药物对60株甲氧西林耐药的金黄色葡萄球菌(MRSA)的最低抑菌浓度,并计算部分抑菌浓度指数(FICI)判定联合效应.结果 氯氰碘柳胺与环丙沙星联合用药后,其FICI分布:FIC≤0.5为20.0％,0.5 ＜FIC≤1为66.7％,1＜FIC≤2为13.3％,FIC＞2为0.结论 体外氯氰碘柳胺与环丙沙星联用对60株耐甲氧西林金黄色葡萄球菌的作用主要为相加和协同作用.     

Permeability of Staphylococcus aureus to the sideromycin antibiotic A 22,765

Summary The sideromycin antibiotic A 22,765 is taken up from the medium by Staphylococcus aureus SG 511 against a concentration gradient. In contrast to this, A 22,765-resistant cells display an extremely low degree of permeability to the molecule. Ferrioxamine B penetrates the cells in only very minute quantities, but nevertheless antagonises permeation by A 22,765. This permeation-antagonising effect of ferrioxamine B is discussed.

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Zusammenfassung Das Sideromycin-Antibioticum A 22,765 wird durch Staphylococcus aureus SG 511 gegen ein Konzentrationsgefälle aus dem Medium aufgenommen. Im Gegensatz dazu zeigen A 22,765-resistente Zellen gegenüber diesem Molekül eine äußerst geringe Permeabilität. Ferrioxamin B dringt nur in sehr geringen Mengen in die Zellen ein, antagonisiert jedoch die Permeation von A 22,765. Die Hemmung dieser Permeation durch Ferrioxamin B wird diskutiert.

     

Oxidative stress induced by ciprofloxacin in Staphylococcus aureus

Staphylococcus aureus with multiple sensitivity to ciprofloxacin, was investigated to detect alterations in the production of superoxide anion (O(2)(-)), other reactive oxidant species (ROS), and superoxide dismutase (SOD), and to relate them with ciprofloxacin accumulation and sensitivity. Oxidative stress was studied by means of Nitroblue Tetrazolium reaction (NBT) and chemiluminescence (CL); lucigenin was employed to detect O(2)(-), and luminol was used to measure other ROS. Sensitive strains exhibited higher intracellular O(2)(-) increase than resistant ones when incubated with ciprofloxacin. SOD was determined in normal conditions and induction was investigated in the presence of ciprofloxacin. These assays demonstrated that resistant and sensitive strains exported a great amount of SOD and that the induction of SOD intracellular was insufficient to counteract the augment of O(2)(-) in the cytoplasm of sensitive strains. Accumulation of ciprofloxacin, researched by spectrofluorometry, showed high levels of antibiotic in sensitive strains which increased the O(2)(-) causing more oxidative stress than in resistant S. aureus.     

Complete Genome of Staphylococcus aureus Phage SA11

A novel lytic bacteriophage, SA11, infecting Staphylococcus aureus was isolated, and the whole genome was sequenced. It belongs to the siphoviridae based on electron microscopic observation. It has a linear double-stranded DNA genome of 136,326 bp. Genomic analysis showed that it is distantly related to Staphylococcus phages A5W, K, ISP, Sb-1, and G1.     

Complete Genome Sequence of Staphylococcus aureus Bacteriophage GH15

GH15 is a polyvalent phage that shows activity against a wide range of Staphylococcus aureus strains. In this work, the complete genome sequence of GH15 was determined. With a genome size of 139,806 bp (double-stranded DNA), GH15 is the largest staphylococcal phage sequenced to date. The complete genome encodes 214 open reading frames (ORFs) and 4 tRNAs. The closest relatives are the class III staphylococcal myobacteriophages, including K, A5W, ISP, Sb-1, and G1. Interestingly, although corresponding gene sequences demonstrate very high similarity, all the introns and inteins present in the phages listed above are absent in GH15. As such, GH15 can be considered phylogenetically unique among the staphylococcal myobacteriophages, indicating the diversity of this family.     

Enhancement of antibiotic activity against Staphylococcus aureus by exposure to hyperbaric oxygen

Growth of Staphylococcus aureus ATCC 6538P was studied in stationary broth cultures (11 mm deep) exposed to hyperbaric oxygen (100% O₂ at 3 atm absolute). The minimal inhibitory concentration (MIC) of the following antibiotics was determined after exposure to high-pressure oxygen (HPO) for 3, 6, and 12 hr: penicillin, streptomycin, tetracycline, oxytetracycline, kanamycin, and cephalothin. Logarithmic growth during exposure to HPO was retarded 60%. Air at 3 atm absolute did not retard growth. The longer the exposure of tube dilution tests to HPO, the lower the MIC. Regardless of the antibiotic used, MIC values relative to 100% for unexposed controls were similar for given exposures, and averaged 73% after 3 hr of exposure to HPO, 53% after 6 hr, and 34% after 12 hr. Similar enhancement with HPO and an iodophor suggests occurrence of a general phenomenon with antibacterial agents. Although HPO alone is primarily bacteriostatic, combined therapy with antibiotics and HPO may be useful against bacterial infections because the therapeutic effectiveness of a maximal dosage of antibiotic could be increased.     

Evolutionary history of Staphylococcus aureus influences antibiotic resistance evolution

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A tactile response in Staphylococcus aureus

It is well established that bacteria are able to respond to temporal gradients (e.g., by chemotaxis). However, it is widely held that prokaryotes are too small to sense spatial gradients. This contradicts the common observation that the vast majority of bacteria live on the surface of a solid substrate (e.g., as a biofilm). Herein we report direct experimental evidence that the nonmotile bacterium Staphylococcus aureus possesses a tactile response, or primitive sense of touch, that allows it to respond to spatial gradients. Attached cells recognize their substrate interface and localize adhesins toward that region. Braille-like avidity maps reflect a cell's biochemical sensory response and reveal ultrastructural regions defined by the actual binding activity of specific proteins.     

Sublethal vancomycin-induced ROS mediating antibiotic resistance in Staphylococcus aureus

Staphylococcus aureus is the leading cause of many human infectious diseases. Besides infectious dangers, S. aureus is well-known for the quickly developed drug resistance. Although great efforts have been made, mechanisms underlying the antibiotic effects of S. aureus are still not well clarified. Recently, reports have shown that oxidative stress connects with bactericidal antibiotics [Dwyer et al. (2009) Curr. Opin. Microbiol. 12, 482–489]. Based on this point, we demonstrate that reactive oxygen species (ROS) induced by sublethal vancomycin may be partly responsible for the antibiotic resistance in heterogeneous vancomycin resistant S. aureus (hVRSA). Sublethal vancomycin treatment may induce protective ROS productions in hVRSA, whereas reduction in ROS level in hVRSA strains may increase their vancomycin susceptibility. Moreover, low dose of ROS in VSSA (vancomycin susceptible S. aureus) strains may promote their survival under vancomycin conditions. Our findings reveal that modest ROS generation may be protective for vancomycin resistance in hVRSA. These results recover novel insights into the relationship between oxidative stress and bacterial resistance, which has important applications for further use of antibiotics and development of therapeutics strategies for hVRSA.     

Complete Genome Sequence of Wide-Host-Range Staphylococcus aureus Phage JD007

Methicillin-resistant Staphylococcus aureus-related infections have become a serious problem worldwide. Bacteriophage therapy is an alternative approach against this threat. S. aureus phage JD007, which belongs to the Myoviridae family according to transmission electron microscopic imaging, could lyse nearly 30% of the S. aureus strains from Ruijin Hospital, Shanghai, China, and was isolated from chicken feces in Shanghai, China. The complete genome showed that JD007 is a linear, double-stranded DNA phage 141,836 bp in length with a GC content of 30.4% encoding 217 open reading frames. A BLAST search of the JD007 genome revealed that it was very similar to that of phage GH15.     

The acid response network of Staphylococcus aureus

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Humoral antibody response to cattle to formalinized Staphylococcus aureus vaccine.

Five cows were inoculated intradermally with formalinized Staphylococcus aureus suspension in Freund's complete adjunvant and the development of the humoral antibody response was followed as judged by the agglutination titer of sera, at various intervals post inoculation. Highest titers were observed at 78-87 days post inoculation. Agglutinating activity was found in IgM and IgG fractions (IgG1 and IgG2) of both serum and colostrum. The agglutinating activity of colostrum was significantly higher at 12 than at 24 and 36 h, post partum. However, no such activity was detected in either normal cow serum or colostrum against S. aureus.