Characterization of Two Different Types of Resistance Genes Among Producers of Fortimicin-Group Antibiotics

Ohta, Toshio; Dairi, Tohru; Hasegawa, Mamoru

doi:10.1099/00221287-139-3-591

Cited by 13 publications

(4 citation statements)

References 42 publications

(35 reference statements)

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“…The fortimicins (astromicins) are produced by actinomycetes from four genera that all contain fortimicin resistance (fmr) genes (Table 1). However, hybridization analysis clearly split the latter genes into two groups (related to fmrT or fmrO, respectively) even though they all confer cross-resistance to kanamycin [161]. The fmrT-related genes also encode low-level neomycin resistance whereas those related to fmrO give gentamicin resistance.…”

Section: Aminoglycosides and Pseudodisaccharidesmentioning

confidence: 97%

Avoidance of suicide in antibiotic-producing microbes

Cundliffe

Demain

2010

J Ind Microbiol Biotechnol

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Many microbes synthesize potentially autotoxic antibiotics, mainly as secondary metabolites, against which they need to protect themselves. This is done in various ways, ranging from target-based strategies (i.e. modification of normal drug receptors or de novo synthesis of the latter in drug-resistant form) to the adoption of metabolic shielding and/or efflux strategies that prevent drug-target interactions. These self-defence mechanisms have been studied most intensively in antibiotic-producing prokaryotes, of which the most prolific are the actinomycetes. Only a few documented examples pertain to lower eukaryotes while higher organisms have hardly been addressed in this context. Thus, many plant alkaloids, variously described as herbivore repellents or nitrogen excretion devices, are truly antibiotics-even if toxic to humans. As just one example, bulbs of Narcissus spp. (including the King Alfred daffodil) accumulate narciclasine that binds to the larger subunit of the eukaryotic ribosome and inhibits peptide bond formation. However, ribosomes in the Amaryllidaceae have not been tested for possible resistance to narciclasine and other alkaloids. Clearly, the prevalence of suicide avoidance is likely to extend well beyond the remit of the present article.

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Section: Aminoglycosides and Pseudodisaccharidesmentioning

confidence: 97%

Avoidance of suicide in antibiotic-producing microbes

Cundliffe

Demain

2010

J Ind Microbiol Biotechnol

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“…These findings might allow the author to insist that actinomycetes with novel profiles of multiple AGR will be an eventual treasure chest of “something new” and that “double stage-acting activity” found in ABK will become a new concept for developing new future AGs. Furthermore, our findings may lead to additional future research as shown in the case of the discovery of ribosomal AG resistance that was linked to the sequential molecular basis analysis of AGR of actinomycetes producing ASTM group AGs by other research groups ( Ohta et al, 1993 ; Piendl et al, 1984 ; Skeggs et al, 1985 ).…”

Section: Closing Remarksmentioning

confidence: 75%

Basic and applied research on multiple aminoglycoside antibiotic resistance of actinomycetes: an old-timer's recollection

Hotta¹

2021

Journal of Industrial Microbiology and Biotechnology

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A list of our research achievements on multiple aminoglycoside antibiotic (AG) resistance in AG-producing actinomycetes is outlined. In 1979, the author discovered a novel AG (istamycin)-producing Streptomyces tenjimariensis SS-939 by screening actinomycetes with kanamycin (KM)-resistance and plasmid profiles. This discovery directed our biochemical and genetic approaches to multiple AG resistance (AGR) of AG producers. In this article, the following discoveries will be outlined: 1. AGR profiles correlating with the productivity of AGs in AG-producers, 2. Wide distribution of multiple AG resistance in AG-nonproducing actinomycetes, 3. Involvement of ribosomal resistance and AG-acetylating enzymes as underlying AGR factors, 4. Activation by single nucleotide substitution of a silent gene coding for aminoglycoside 3-N-acetyltransferase, AAC(3), in S. griseus, 5. Discovery of a novel antibiotic indolizomycin through protoplast fusion treatment between S. tenjimariensis and S. griseus strains with different AGR phenotypes and 6. Double stage-acting activity of arbekacin (ABK; an anti-MRSA semisynthetic AG) discovered by acetylation of ABK with cloned AACs; i.e. both ABK and its acetylated derivatives showed remarkable antibiotic activities.

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“…Comparison of the predicted amino acid sequence encoded by this ORF of S. kanamyceticus 1 (277 aa) with various databases revealed similarities with KamB 16SrRNA methylase from the nebramycin complex producer S. tenebrarius (53.9% aa identity, 274 aa overlapping) , GrmB and Sgm methylases from the sisomicin producers Micromonospora rosea (51.5%, 274 aa) and M. zionensis (52.2%, 274 aa) (KOJIC et al 1992), with GrmA methylase from the gentamicin producer M. purpurea (51.3%, 277aa) (KELEMEN et al 1991) and FmrO from the fortimicin producer M. olivasterospora (35%, 254 aa) (OHTA et al 1993). These enzymes confer very similar phenotypes.…”

Section: Nucleotide Sequence Of the Kmr-determinantmentioning

confidence: 99%