Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. II: Structure elucidation

Uchida, Ryuji; Iwatsuki, Masato; Kim, Yong-Pil; Ōmura, Satoshi; Tomoda, Hiroshi

doi:10.1038/ja.2010.10

Cited by 20 publications

(22 citation statements)

References 13 publications

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“…Furthermore, nosokomycin A was also found to be effective in an in vivo system using a mouse model (data not shown). As described in the accompanying study, 9 nosokomycins are structurally related to moenomycins 10 ( Figure 1). Nosokomycin B is identical to the semisynthetic moenomycin A derivative, 11 which lacks the chromophoric cyclopentenone moiety.…”

Section: Discussionmentioning

confidence: 81%

“…After Mueller-Hinton broth (90 ml) was added to each well of a 96-well microtiter plate (Corning Inc., Corning, NY, USA), a sample dissolved in methanol (5 ml) was added. 9 Finally, MRSA (5 ml) was added at a concentration of 1Â10 7 CFU ml À1 . Microtiter plates were incubated at 37 1C for 20 h without shaking.…”

Section: Assay For Anti-mrsa Activitymentioning

confidence: 99%

“…The structure elucidation of nosokomycins is reported in an accompanying paper. 9 In this study, the fermentation, isolation and biological properties of nosokomycins are described.…”

Section: Introductionmentioning

confidence: 99%

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Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties

et al. 2010

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The in vivo-mimic assay system using silkworm larvae was used as a screening tool to discover antibiotics against methicillinresistant Staphylococcus aureus (MRSA). Microbial culture broths were screened in this in vivo-mimic assay system and a culture broth of Streptomyces sp. K04-0144 was selected. New antibiotics, designated nosokomycins A-D, were isolated from the culture broth by HP-20 and ODS column chromatography and HPLC. Nosokomycins inhibited the growth of MRSA with MIC values of 0.125 lg ml À1 using the liquid microdilution method. Furthermore, MRSA-infected silkworms survived when nosokomycin A or B was injected at a dose of 50 lg per larva.

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Section: Discussionmentioning

confidence: 81%

Section: Assay For Anti-mrsa Activitymentioning

confidence: 99%

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Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties

et al. 2010

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“…8) They are structurally related to moenomycins, 14) which consist of a polyprenyl chain, a phosphoglycerate, and a carbohydrate chain (pentasaccharide). Moenomycins were known to inhibit the transglycosylase of penicillin binding protein (PBP) involved in bacterial peptidoglycan biosynthesis, 15,16) suggesting that the target molecule of nosokomycins is transglycosylase.…”

Section: Screening For Anti-mrsa Antibiotics In Silkworm Infection Assaymentioning

confidence: 99%

New Approaches to Drug Discovery for Combating MRSA

Tomoda

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Methicillin-resistant Staphylococuss aureus (MRSA) is a major nosocomial pathogen that has developed resistance to many antibiotics. New anti-infective drugs to prevent and treat MRSA infection are required. Four assay systems were conducted to screen microbial cultures for new anti-infective compounds active against MRSA. Nosokomycins, new members of the phosphoglycolipid family, were discovered from a culture of Streptomyces cyslabdanicus K04-0144 in an MRSA-silkworm infection assay. The target molecule of nosokomycins was suggested to be the transglycosylase of penicillin binding protein (PBP) involved in MRSA peptidoglycan biosynthesis. Spirohexaline, with a hexacycline structure, was isolated from a fungal culture of Penicillium brasilianum FKI-3368 in an enzyme assay of undecaprenyl pyrophosphate (UPP) synthase, which is needed for the synthesis and transport of GlcNAc-MurNAc-pentapeptides from the cytoplasmic membrane site to the external membrane site for peptidoglycan synthesis. Spirohexaline inhibited MRSA growth by the blockade of UPP synthase activity. Cyslabdan, with a cysteine-carrying labdan skeleton, was also discovered from the nosokomycin-producing actinomycete as a potentiator of imipenem activity against MRSA. The molecular target of cyslabdan was identified as FemA, which is involved in the synthesis of a pentaglycine interpeptide bridge in MRSA peptidoglycan. Citridone A with a unique 6-6/5/5-ring system containing a rare phenyl-R-furopyridone skeleton, originally isolated as a potentiator of antifungal miconazole activity, was found to inhibit MRSA yellow pigment production. These new microbial products will serve as lead compounds for developing new anti-infective drugs for combating MRSA.

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“…In this assay, candidate compounds or test samples are injected into pathogenic microorganism-infected silkworm larvae and the survival rate over a few days is then evaluated. In a silkworm infection model with methicillin-resistant Staphylococcus aureus (MRSA), nosokomycins (2)(3)(4), and lysocins in bacterial culture broths were identified as effective in vivo anti-MRSA antibiotics (1).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of three trichothecenes in the silkworm infection assay with <i>Candida albicans </i>

Uchida

Namiguchi

Ishijima

et al. 2016

DD&T

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Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. II: Structure elucidation

Cited by 20 publications

References 13 publications

Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties

Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties

New Approaches to Drug Discovery for Combating MRSA

Therapeutic effects of three trichothecenes in the silkworm infection assay with <i>Candida albicans </i>

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