Norihisa Noguchi

Publications of Norihisa Noguchi

• Novel anti-acne actions of nadifloxacin and clindamycin that inhibit the production of sebum, prostaglandin E(2) and promatrix metalloproteinase-2 in hamster sebocytes.

  Authors: Takashi Sato, Tatsuhiko Shirane, Norihisa Noguchi, Masanori Sasatsu, Akira Ito

  The Journal of dermatology. 03/2012;

  Acne vulgaris is characteristic of excess sebum production and the induction of inflammatory reactions, for example, the augmentation of cytokine, prostaglandin (PG) and matrix metalloproteinaseAcne vulgaris is characteristic of excess sebum production and the induction of inflammatory reactions, for example, the augmentation of cytokine, prostaglandin (PG) and matrix metalloproteinase (MMP) production in sebaceous glands and pilosebaceous units. As Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, antimicrobial agents have been found to be effective for treating acne leading to the remission of inflammation. However, it is not fully understood whether antimicrobial agents influence sebum production and/or the inflammatory reactions in sebaceous gland cells (sebocytes). In the present study, topical antimicrobial agents such as nadifloxacin (NDFX) and clindamycin (CLDM) decreased the production of triacylglycerols (TG), which are a major component of sebum in insulin-differentiated hamster sebocytes. These antibiotics also suppressed insulin-augmented gene expression and the production of perilipin, by which intracellular lipid droplet formation was concomitantly inhibited. On the other hand, peptidoglycan (PGN) from Gram-positive bacteria dose-dependently increased TG production in hamster sebocytes. The augmented TG production was decreased by treating NDFX or CLDM. Furthermore, NDFX and CLDM inhibited the PGN-augmented PGE(2) production in the sebocytes. Moreover, NDFX, but not CLDM, suppressed the PGN-augmented gene expression and production of pro-MMP-2/progelatinase A in hamster sebocytes. Therefore, these results provide novel evidence that NDFX and CLDM exhibit anti-lipogenesis and anti-inflammatory activities against insulin- or PGN-activated sebocytes which at least partly mimic acne pathology in vitro. Moreover, NDFX for acne therapy is likely to be effective in not only inhibiting microbial proliferation but also in preventing the onset of acne scar formation.

• Fluoroquinolone resistance in Helicobacter pylori: role of mutations at position 87 and 91 of GyrA on the level of resistance and identification of a resistance conferring mutation in GyrB.

  Authors: Emiko Rimbara, Norihisa Noguchi, Takashi Kawai, Masanori Sasatsu

  Helicobacter. 02/2012; 17(1):36-42.

  Fluoroquinolone-containing regimens have been suggested as an alternate to standard triple therapy for the treatment of Helicobacter pylori infections. To determine the relationship betweenFluoroquinolone-containing regimens have been suggested as an alternate to standard triple therapy for the treatment of Helicobacter pylori infections. To determine the relationship between fluoroquinolone resistance and mutations of GyrA and GyrB in H. pylori, we exchanged the mutations at positions 87 and 91 of GyrA among fluoroquinolone-resistant clinical isolates. GyrB of a strain with no mutations in GyrA was also analyzed to identify mechanisms of resistance to norfloxacin. Natural transformation was performed using the amplified fragment of the gyrA and gyrB gene as donor DNA. The amino acid sequences of GyrA and GyrB were determined by DNA sequencing of the gyrA and gyrB genes. Norfloxacin-resistant strains which had mutations at position 87 and 91 became susceptible when the mutations were converted to the wild type. When the mutation from Asp to Asn at position 91 was exchanged to the mutation from Asn to Lys at position 87, the MIC to levofloxacin, gatifloxacin, and sitafloxacin increased. Norfloxacin-resistant strain TS132 with no mutations in GyrA but had a mutation at position 463 in GyrB. Transformants obtained by natural transformation using gyrB DNA of TS132 had a mutation at position 463 of GyrB and revealed resistant to norfloxacin and levofloxacin. Mutation from Asn to Lys at position 87 of GyrA confers higher resistance to levofloxacin and gatifloxacin than does mutation from Asp to Asn at position 91. We propose that mutation at position 463 in GyrB as a novel mechanism of fluoroquinolone resistance in H. pylori.

• First report of high levels of clindamycin-resistant Propionibacterium acnes carrying erm(X) in Japanese patients with acne vulgaris.

  Authors: Keisuke Nakase, Hidemasa Nakaminami, Norihisa Noguchi, Setsuko Nishijima, Masanori Sasatsu

  The Journal of dermatology. 12/2011;

• Effect of Pretreatment with Lactobacillus gasseri OLL2716 on First-line Helicobacter pylori Eradication Therapy.

  Authors: Ryuzo Deguchi, Hidemasa Nakaminami, Emiko Rinbara, Norihisa Noguchi, Masanori Sasatsu, Takayoshi Suzuki, Masashi Matsushima, Jun Koike, Muneki Igarashi, Hideki Ozawa, Ryuki Fukuda, Atsushi Takagi

  Journal of gastroenterology and hepatology. 11/2011;

  Background: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70 to 90% of cases, but treatment failures due to poor patientBackground: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70 to 90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. Lactobacillus gasseri can suppress both clarithromycin-susceptible and -resistant strains of H. pylori in vitro. Aim: To determine the effect of pretreatment with L. gasseri- containing yogurt on H. pylori eradication, we conducted a randomized, controlled clinical trial in patients with H. pylori infection. Methods: Two hundred and twenty-nine patients were randomized either to a 1-week triple therapy of rabeprazole (10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200mg bid) or triple therapy plus L.gasseri-containing yogurt. In the yogurt-plus-triple therapy groups yogurt containing L. gasseri OLL2716 (112 g) was given twice daily for 4 weeks (3- week pretreatment and also 1 week during eradication therapy). Clarithromycin resistance was determined by the detection of a mutation in 23S rRNA using nested PCR and the direct sequencing of DNA from pretreatment feces. H. pylori eradication was diagnosed based on the UBT and a stool antigen test after 8 weeks of eradication. Results: The status of H. pylori susceptibility to clarithromycin was successively determined in 188 out of 229 samples. The rate of infection with clarithromycin-resistant strains of H. pylori was 27.1%. Overall eradication (intention to treat/ per protocol) was 69.3/74.5 % for the triple-only group, and 82.6/85.6 % for the yogurt-plus-triple group (p = 0.018/p = 0.041). Eradication of primary clarithromycin-resistant strains tended to be higher for yogurt-plus-triple therapy than triple-only therapy. (38.5 vs. 28.0%, respectively, p = 0.458). Conclusion: This study confirmed that the major cause of treatment failure is resistance to clarithromycin. A 4-week treatment with L. gasseri-containing yogurt improves the efficacy of triple therapy in patients with H. pylori infection.

• Susceptibility of Propionibacterium acnes isolated from patients with acne vulgaris to zinc ascorbate and antibiotics.

  Authors: Katsuhiro Iinuma, Norihisa Noguchi, Hidemasa Nakaminami, Masanori Sasatsu, Setsuko Nishijima, Isami Tsuboi

  Clinical, cosmetic and investigational dermatology. 01/2011; 4:161-5.

  The in vitro antimicrobial activity of ascorbic acid derivatives against Propionibacterium acnes was tested either alone or in combination with a variety of antimicrobial agents, and their fractionalThe in vitro antimicrobial activity of ascorbic acid derivatives against Propionibacterium acnes was tested either alone or in combination with a variety of antimicrobial agents, and their fractional inhibitory concentration index was determined using checkerboard tests. The antimicrobial effectiveness of zinc ascorbate in the treatment of acne vulgaris, either alone or in combination with antibiotics such as clindamycin that are commonly used in Japan for the treatment of acne vulgaris, was therefore examined. The antimicrobial susceptibility of 41 strains of clindamycin-sensitive and/or clindamycin-resistant P. acnes isolated from acne vulgaris patients was tested, in comparison with a type strain of P. acnes. Zinc ascorbate showed antimicrobial activity against a type strain of P. acnes and its concentration (0.064%) was sufficiently lower than the normal dose (5%) of other ascorbic acid derivatives. Combinations of zinc ascorbate with clindamycin, erythromycin, and chloramphenicol showed an additive effect, and zinc ascorbate alone effectively inhibited the growth of all P. acnes including clindamycin-resistant strains. The results provide novel evidence that the combination of zinc ascorbate and clindamycin is effective for acne vulgaris treatment.

• Augmentation of gene expression and production of promatrix metalloproteinase 2 by Propionibacterium acnes-derived factors in hamster sebocytes and dermal fibroblasts: a possible mechanism for acne scarring.

  Authors: Takashi Sato, Hirokazu Kurihara, Noriko Akimoto, Norihisa Noguchi, Masanori Sasatsu, Akira Ito

  Biological & pharmaceutical bulletin. 01/2011; 34(2):295-9.

  Aberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement ofAberrant extracellular matrix (ECM) remodeling in sebaceous glands and pilosebaceous units in the skin is associated with scar formation under acne conditions. To investigate the involvement of Propionibacterium acnes (P. acnes), a Gram-positive anaerobic microbial species, in ECM remodeling in sebaceous glands and pilosebaceous units, we examined the effects of P. acnes culture media, formalin-fixed P. acnes, and peptidoglycan (PGN) from Gram-positive bacteria walls on the production of promatrix metalloproteinase 2 (proMMP-2)/progelatinase A in hamster sebocytes and dermal fibroblasts. When hamster sebocytes (1.8×10(5) cells) and dermal fibroblasts (1×10(5) cells) were treated with P. acnes culture media and formalin-fixed P. acnes (corresponding to 1×10(6) and 1×10(7) bacterial cells), the production of proMMP-2 was augmented. In addition, PGN (5-50 µg/ml) dose-dependently augmented the production of proMMP-2 in both cells. Furthermore, the PGN (50 µg/ml)-augmented proMMP-2 production was resulted from an increase of its transcript. In contrast, there were no changes in cell proliferative activity in either the P. acnes or PGN-treated sebocytes and dermal fibroblasts, indicating that the augmented proMMP-2 production was not due to an increase in cell numbers. Therefore, these results provide novel evidence that PGN transcriptionally up-regulates the production of proMMP-2 in hamster sebocytes and dermal fibroblasts. Given an increase in the quantity of Gram-positive bacteria, including P. acnes in acne lesions, the aberrant ECM degradation may progress in sebaceous glands and pilosebaceous units, which is associated with acne scar formation.

• [Antimicrobial activity and frequency of spontaneous gentamicin-resistant mutants in bacteria related skin infections].

  Authors: Mao Iwaki, Norihisa Noguchi, Hidemasa Nakaminami, Masanori Sasatsu, Masatoshi Ito

  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 01/2011; 131(11):1653-9.

  Gentamicin is used in an ointment form for the treatment of skin infections. To investigate the effect of gentamicin used as an ointment, the antimicrobial susceptibilities against StaphylococcusGentamicin is used in an ointment form for the treatment of skin infections. To investigate the effect of gentamicin used as an ointment, the antimicrobial susceptibilities against Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pyogenes, and Pseudomonas aeruginosa isolated from community and medical settings were studied and compared with other antibacterial agents such as fradiomycin, chloramphenicol, and bacitracin used as active ingredient for each ointment. Gentamicin showed antibacterial activities for all standard bacteria tested, but fradiomycin and chloramphenicol showed no such activities for St. pyogenes and P. aeruginosa, respectively. Bacitracin showed activity for St. pyogenes only. The strains of staphylococci isolated from healthy people were highly susceptible to gentamicin, while 49.3% of the isolates from the patients with skin infections were resistant to gentamicin and 96.4% of the gentamicin-resistant staphylococci carried the aminoglycoside-resistance gene aacA-aphD. The growths of all strains tested, except for two strains of P. aeruginosa, were inhibited by close below 128 µg/ml of gentamicin. Furthermore, the frequencies of spontaneous mutants resistant to gentamicin, fradiomycin, and chloramphenicol were each investigated using S. aureus, S. epidermidis, St. pyogenes, and P. aeruginosa. At doses of more than 32 µg/ml of gentamicin, no resistant mutants in any of bacteria strains tested were obtained. The concentration of gentamicin on the skin was calculated at approximately 895 µg/ml at least when the commercially used 0.1% gentamicin ointment was applied to the skin. Therefore, our study strongly indicates that the gentamicin ointment used has a potency of sufficiently inhibiting the growth of bacteria, including gentamicin-resistant strains, which cause skin infections in the community.

• Characterization of enterococcus strains contained in probiotic products.

  Authors: Norihisa Noguchi, Hidemasa Nakaminami, Keisuke Nakase, Masanori Sasatsu

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1469-73.

  Probiotics are additives containing live microbes that beneficially affect a host by improving the properties of the host intestinal microflora. Recently, advances in medical treatments have led toProbiotics are additives containing live microbes that beneficially affect a host by improving the properties of the host intestinal microflora. Recently, advances in medical treatments have led to increased numbers of immunocompromised patients; some patients contract opportunistic infections of Enterococcus species, which are considered non-pathogenic bacteria. To evaluate the safety of probiotics containing Enterococcus strains, we isolated Enterococcus from six probiotic products and compared the pathogenic genes and antimicrobial susceptibility of the probiotic strains to those of clinical isolates. Our study showed that all Enterococcus strains contained in probiotic products were E. faecium, and no vancomycin-resistant strains were found. In addition, no pathogenic genes, such as ace, agg, gelE, cylM, cylB, cylA, cpd, cob, ccf, efaA(fs), efaA(fm), esp(fs), or esp(fm), were found in the probiotic strains. Pulsed-field gel electrophoresis (PFGE) analysis showed obvious genetic differences between the probiotic strains and the clinical isolates. The data suggested that the probiotic Enterococcus strains were not transmitted to hospitalized patients. Therefore, our results strongly suggest that probiotic products are unlikely agents for causing opportunistic infections.

• Fluoroquinolone efflux by the plasmid-mediated multidrug efflux pump QacB variant QacBIII in Staphylococcus aureus.

  Authors: Hidemasa Nakaminami, Norihisa Noguchi, Masanori Sasatsu

  Antimicrobial agents and chemotherapy. 10/2010; 54(10):4107-11.

  Plasmids that carry the multidrug efflux genes qacA and qacB are widely distributed in methicillin-resistant Staphylococcus aureus (MRSA). Although the QacA and QacB proteins are similar to eachPlasmids that carry the multidrug efflux genes qacA and qacB are widely distributed in methicillin-resistant Staphylococcus aureus (MRSA). Although the QacA and QacB proteins are similar to each other, their respective substrate specificities may differ. We investigated the variability and structure-function relationships of QacA and QacB in MRSA isolates. The amino acid sequences of 7 QacA and 25 QacB proteins showed that QacB was present in three variants, designated QacBII, QacBIII, and QacBIV, that were different from the prototypic QacB variant encoded by plasmid pSK23, which was named QacBI, while QacA was present in two variants. When cloned and expressed in S. aureus, the strain carrying qacBIII exhibited higher susceptibility to dyes and decreased susceptibility to norfloxacin and ciprofloxacin compared to strains carrying the other QacB variants. Site-directed mutagenesis experiments revealed that the residue at position 320 in QacB plays an important role in the resistance phenotypes to dyes and fluoroquinolones. Furthermore, the accumulation of norfloxacin and ciprofloxacin in the strain carrying qacBIII was significantly decreased. Our data demonstrate that the plasmid-mediated multidrug efflux pump QacB variant QacBIII confers the capability for fluoroquinolone efflux on S. aureus.

• Analysis of Clarithromycin Resistance and CagA Status in Helicobacter pylori Using Feces from Children in Thailand.

  Authors: Michiya Tanuma, Emiko Rimbara, Norihisa Noguchi, Surasak Boonyaritichaikij, Kentaro Kuwabara, Yoshitaka Fukunaga, Masanori Sasatsu

  Journal of clinical microbiology. 09/2009;

  The clarithromycin resistance and CagA status of Helicobacter pylori in Thai children was investigated using fecal samples. Of the 284 samples, H. pylori was detected in 120 samples, and theThe clarithromycin resistance and CagA status of Helicobacter pylori in Thai children was investigated using fecal samples. Of the 284 samples, H. pylori was detected in 120 samples, and the clarithromycin resistance rate was 29.2%. The cagA gene was detected in 59 samples, and only 6.8% of these samples encoded the East Asian CagA.

• Using the tannase gene to rapidly and simply identify Staphylococcus lugdunensis.

  Authors: Norihisa Noguchi, Keiko Goto, Tokihiro Ro, Koji Narui, Mari Ko, Yutaka Nasu, Kenta Utsumi, Kenji Takazawa, Fuminori Moriyasu, Masanori Sasatsu

  Diagnostic microbiology and infectious disease. 06/2009;

  The coagulase-negative Staphylococcus lugdunensis, a bacterium similar to Staphylococcus aureus, produces tannase that degrades tannin. We developed a polymerase chain reaction-based method toThe coagulase-negative Staphylococcus lugdunensis, a bacterium similar to Staphylococcus aureus, produces tannase that degrades tannin. We developed a polymerase chain reaction-based method to rapidly and simply identify this species by detecting the tanA gene for S. lugdunensis tannase.

• Evaluation of clarithromycin resistance in Helicobacter pylori obtained from culture isolates, gastric juice, and feces.

  Authors: Emiko Rimbara, Remi Tamura, Michiya Tanuma, Norihisa Noguchi, Takashi Kawai, Masanori Sasatsu

  Helicobacter. 05/2009; 14(2):156-7.

• Involvement of Propionibacterium acnes in the Augmentation of Lipogenesis in Hamster Sebaceous Glands In Vivo and In Vitro.

  Authors: Katsuhiro Iinuma, Takashi Sato, Noriko Akimoto, Norihisa Noguchi, Masanori Sasatsu, Setsuko Nishijima, Ichiro Kurokawa, Akira Ito

  The Journal of investigative dermatology. 04/2009;

  Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, but it remains unclear whether P. acnes directly influences lipogenesis in sebaceous glands. In this study,Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, but it remains unclear whether P. acnes directly influences lipogenesis in sebaceous glands. In this study, we showed that a culture medium of P. acnes (acnes-CM) and formalin-killed P. acnes (F-acnes) prepared from P. acnes strains, JCM6473 and JCM6425, intracellularly augmented lipid droplet formation and triacylglycerol (TG) synthesis in undifferentiated and insulin-differentiated hamster sebocytes. Acnes-CM and F-acnes prepared from four clinical P. acnes strains elicited the same lipogenesis augmentation. The augmented TG production resulted from an increase in the diacylglycerol acyltransferase activity. Topical application of acnes-CM to the skin of hamster auricles every day for 4 weeks revealed that sebum accumulation was augmented in sebaceous glands and ducts. Furthermore, both acnes-CM and F-acnes increased the production of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a cytochrome P450 (CYP)-linked sebaceous lipogenic factor, in differentiated sebocytes. A CYP inhibitor, SKF-525A, decreased the acnes-CM- and F-acnes-augmented production of TG and 15d-PGJ(2). Thus, to our knowledge these results provide previously unreported evidence that P. acnes directly participates in the augmentation of sebaceous lipogenesis through a proposed mechanism in which an increase of 15d-PGJ(2) production through the CYP pathway is closely associated with the enhancement of TG production.Journal of Investigative Dermatology advance online publication, 12 March 2009; doi:10.1038/jid.2009.46.

• Tailored eradication therapy based on fecal Helicobacter pylori clarithromycin sensitivities.

  Authors: Takashi Kawai, Tetsuya Yamagishi, Kenji Yagi, Mikinori Kataoka, Kohei Kawakami, Atsushi Sofuni, Takao Itoi, Yoshihiro Sakai, Fuminori Moriyasu, Yoshiaki Osaka, Yu Takagi, Tatsuya Aoki, Emiko Rimbara, Norihisa Noguchi, Masanori Sasatsu

  Journal of gastroenterology and hepatology. 01/2009; 23 Suppl 2:S171-4.

  BACKGROUND AND AIM: Helicobacter pylori (H. pylori) eradication rates using the PPI/AC regimen (proton pump inhibitor + amoxicillin + clarithromycin) are declining. We trialed tailoring eradicationBACKGROUND AND AIM: Helicobacter pylori (H. pylori) eradication rates using the PPI/AC regimen (proton pump inhibitor + amoxicillin + clarithromycin) are declining. We trialed tailoring eradication regimens according to clarithromycin (CAM) susceptibility. METHODS: The subjects were 70 H. pylori positive adults. They were randomly allocated to a tailored group and a control group. In the tailored group, subjects with CAM-sensitive strains were given PPI/AC eradication therapy, and those with CAM-resistant strains were given PPI/AM (metronidazole instead of clarithromycin) therapy. The control group were all given PPI/AC therapy. CAM sensitivity was measured by collecting fecal specimens, and extracting the DNA. The 23S rRNA domain, associated with CAM susceptibility in H. pylori, was amplified using a nested polymerase chain reaction (PCR), and DNA sequencing was used to detect point mutations at A2143G and A2144G. RESULTS: Eradication rates were 94.3% in the tailored group and 71.4% in the control group. In particular, the eradication rate was 100% for CAM-resistant strains in the tailored group. CONCLUSIONS: In Japan, where CAM-resistant H. pylori strains are expected to continue to increase, tailored eradication therapy according to CAM sensitivity will be of benefit.

• Anti-infectious Activity of Tryptophan Metabolites in the L-Tryptophan-L-Kynurenine Pathway.

  Authors: Koji Narui, Norihisa Noguchi, Aya Saito, Kazuhiro Kakimi, Noboru Motomura, Kinya Kubo, Shinichi Takamoto, Masanori Sasatsu

  Biological & pharmaceutical bulletin. 01/2009; 32(1):41-4.

  To study the anti-infectious effect of a vascular allograft, the antimicrobial activity of tryptophan metabolites mediated by indoleamine 2,3-dioxygenase was determined. The growth ofTo study the anti-infectious effect of a vascular allograft, the antimicrobial activity of tryptophan metabolites mediated by indoleamine 2,3-dioxygenase was determined. The growth of methicillin-resistant Staphylococcus aureus (MRSA) over 10 h in extracts from post-transplantation vascular allograft was significantly slower than that of extracts from non-transplantation vascular allograft regardless of the presence of tryptophan (p<0.05). When the antimicrobial activity of the tryptophan metabolites in the L-tryptophan-L-kynurenine pathway was examined, 3-hydroxy-DL-kynurenine and alpha-picolinic acid had strong antibacterial activity against MRSA, S. epidermidis, Escherichia coli, and multidrug-resistant Pseudomonas aeruginosa, although antimicrobial activities of anthranilic acid, 3-hydroxyanthranilic acid, and quinolinic acid against them were low. The results showed that, of the tested tryptophan metabolites, 3-hydroxy-DL-kynurenine and alpha-picolinic acid contributed to the anti-infectious effects of the allograft by inhibiting of the growth of microorganisms.

• Antimicrobial susceptibilities of Propionibacterium acnes isolated from patients with acne vulgaris.

  Authors: Natsumi Ishida, Hidemasa Nakaminami, Norihisa Noguchi, Ichiro Kurokawa, Setsuko Nishijima, Masanori Sasatsu

  Microbiology and immunology. 01/2009; 52(12):621-4.

  Antibiotic susceptibilities of Propionibacterium acnes in Japan were determined. Erythromycin-resistance was found in 10.4% (5/48) of the strains, and four of these were cross-resistance toAntibiotic susceptibilities of Propionibacterium acnes in Japan were determined. Erythromycin-resistance was found in 10.4% (5/48) of the strains, and four of these were cross-resistance to clindamycin. Although the erythromycin ribosome methylase gene erm(X) was looked for, no strain carrying erm(X) was found. Sequencing analysis revealed that all of the erythromycin-resistant strains had a mutation in the peptidyl transferase region of the 23S rRNA gene: G2057A, A2058G, or A2059G. Consequently, our results show that P. acnes resistance to macrolides is caused by a mutation in the 23S rRNA gene, and has been increasing in Japan.

• Molecular epidemiology and antimicrobial susceptibilities of 273 exfoliative toxin-encoding-gene-positive Staphylococcus aureus isolates from patients with impetigo in Japan.

  Authors: Hidemasa Nakaminami, Norihisa Noguchi, Masami Ikeda, Mikiko Hasui, Minoru Sato, Shinji Yamamoto, Tomoko Yoshida, Takashi Asano, Mitsura Senoue, Masanori Sasatsu

  Journal of medical microbiology. 11/2008; 57(Pt 10):1251-8.

  The molecular epidemiology and antimicrobial susceptibilities of 273 Staphylococcus aureus isolates positive for the exfoliative toxin-encoding gene obtained from patients with impetigo in Japan inThe molecular epidemiology and antimicrobial susceptibilities of 273 Staphylococcus aureus isolates positive for the exfoliative toxin-encoding gene obtained from patients with impetigo in Japan in 2006 were studied. The mecA gene was detected in 74 meticillin-resistant S. aureus (MRSA) and 23 meticillin-susceptible S. aureus (MSSA) isolates. All isolates with the staphylococcal cassette chromosome (SCC) mec were classified into type IV (92.8 %, 90/97) or V (7.2 %, 7/97). The ET-encoding gene etb was found primarily in strains with mecA (87.7 %, 71/81), whilst eta (86.6 %, 161/186) was detected mainly in strains without mecA. The chromosomal enterotoxin-encoding gene cluster egc was found in 83.0 % of strains with eta, whilst no enterotoxin-encoding gene was detected in strains with only etb. PFGE showed that each strain carrying eta, etb and etd could be classified into distinct groups. The susceptibility profiles of MRSA to antimicrobial agents excluding beta-lactams were similar to those of MSSA. Gentamicin- and clarithromycin-resistant strains were frequently found for both MRSA and MSSA. The aminoglycoside-resistance gene aacA-aphD was detected in 97.3 % of MRSA and 85.4 % of MSSA. Additionally, the macrolide-resistance gene ermA or ermC was detected in 67.6 % of MRSA and 71.4 % of MSSA. Therefore, these results suggest that SCCmec types IV or V have spread, particularly in MSSA carrying etb in the community.

• Anti-infectious effect of S-benzylisothiourea compound A22, which inhibits the actin-like protein, MreB, in Shigella flexneri.

  Authors: Norihisa Noguchi, Keita Yanagimoto, Hidemasa Nakaminami, Moeru Wakabayashi, Noritaka Iwai, Masaaki Wachi, Masanori Sasatsu

  Biological & pharmaceutical bulletin. 08/2008; 31(7):1327-32.

  S-Benzylisothiourea compound A22 induces coccoid forms in Escherichia coli by inhibiting the function of the actin-like cytoskeletal protein, MreB. The minimum inhibitory concentration of A22 and theS-Benzylisothiourea compound A22 induces coccoid forms in Escherichia coli by inhibiting the function of the actin-like cytoskeletal protein, MreB. The minimum inhibitory concentration of A22 and the minimum concentration to induce coccoid forms for various pathogenic bacteria were determined. At 10 microg/ml, A22 induced coccoid forms in Shigella flexneri but did not inhibit the growth. No alteration of coccoid forms in the Gram-positive bacteria and anaerobic bacteria tested were observed following treatment with A22. To study the relationship between pathogenicity and alterations in bacterial shape, the infectious capacity of A22-induced coccoid S. flexneri was examined using CHO-K1 cells. Invasion of the coccoid cells was significantly reduced, however, no changes in adherence were observed. Using a mutant defective in the type III secretion apparatus, which delivers effectors to the host, we examined the secretion of effectors by A22-induced coccoid S. flexneri. The amount of secreted effectors in the coccoid cells was clearly decreased compared to rod-shaped cells. These results showed that the maintenance of rod-shaped cells by MreB in bacteria was essential for the secretion of effectors via the type III secretion system. Therefore, our results suggest that A22 is a useful lead compound for a novel anti-infectious agent without bactericidal activity and MreB is a candidate target site for development of new anti-infectious agents.

• Identification of a novel mutation in 23S rRNA, which confers low-level resistance to clarithromycin in Helicobacter pylori.

  Authors: Emiko Rimbara, Norihisa Noguchi, Takashi Kawai, Masanori Sasatsu

  Antimicrobial agents and chemotherapy. 08/2008;

  In many countries, the occurrence of clarithromycin-resistant Helicobacter pylori has become increasingly common. ...

• Characterization of the pTZ2162 encoding multidrug efflux gene qacB from Staphylococcus aureus.

  Authors: Hidemasa Nakaminami, Norihisa Noguchi, Setsuko Nishijima, Ichiro Kurokawa, Masanori Sasatsu

  Plasmid. 07/2008;

  The plasmid-borne multidrug efflux gene qacB is widely distributed in methicillin-resistant Staphylococcus aureus (MRSA). We analyzed the complete nucleotide sequence of the plasmid pTZ2162 (35.4kb)The plasmid-borne multidrug efflux gene qacB is widely distributed in methicillin-resistant Staphylococcus aureus (MRSA). We analyzed the complete nucleotide sequence of the plasmid pTZ2162 (35.4kb) encoding qacB. The plasmid pTZ2162 contains 47 ORFs and four copies of IS257 (designated IS257A to D). The 24.7-kb region of pTZ2162, which excluding the region flanked by IS257A and IS257D, is 99.9% identical to pN315 carried by MRSA N315. However, the repA-like region of pTZ2162 was divided into two ORFs, ORF46 and ORF47. Functional analysis with the pUC19-based vector pTZN03 showed that both ORF46 and ORF47 were essential for the replication of pTZ2162 and ORF1 is required for the stable maintenance of pTZ2162 in S. aureus. When pTZ2162 was searched for evidence of mobile elements, an 8-bp duplicated sequence (GATAAAGA) was existed at the left boundary of IS257A and the right boundary of IS257D. Therefore, the 10.7-kb region between IS257A and IS257D in pTZ2162 has the potential to act as a transposon. In addition to qacB, the pTZ2162 transposon-like element contains a novel fosfomycin resistance determinant fosD and an aminoglycoside resistance determinant aacA-aphD. This transposon-like element appears to have translocated into the beta-lactamase gene blaZ. Our data suggest that qacB is transferred between MRSA as a multiple antibiotic resistance transposon.