New approaches to antibiotic discovery

Kealey, Carmel; Creaven, C A; Murphy, Cormac D.; Brady, Damien

doi:10.1007/s10529-017-2311-8

Cited by 62 publications

(61 citation statements)

References 63 publications

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“…It has become critical to develop novel antibiotics to overcome forth coming challenge of treating infectious diseases. 26,27 We were interested if any of the soil bacterial isolates has the ability to produce chemicals that inhibit other bacterial growth. All the isolates were tested for antibacterial activity against both gram positive and gram negative bacteria (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of Bacteria with Biochemical and Pharmacological Importance from Soil Samples of Dhaka City

Begum

Mannan

Rezwan

et al. 2017

Dhaka Univ. J. Pharm. Sci

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Abstract:We studied soil samples from Dhaka municipality area to isolate and characterize bacteria having potential biochemical and pharmacological importance. Total twenty five soil samples were collected from fish, vegetables and fruits dump area from Dhaka City. Bacterial population was sub-cultured in trypticase soya agar (TSA) plate.Nineteen colonies were isolated, cultured and characterized by gram staining and biochemical tests. Six isolates were found to be gram negative while thirteen were gram positive. All isolates were positive in oxidase, catalase, citrate, and protease tests. Eight isolates showed coagulase negative and nine were coagulase positive. It was found that all bacterial isolates were sensitive to tetracycline, chloramphenicol, gentamycin, ciprofloxacin, azithromycin and ceftriaxone. About 95% of the bacterial isolates were resistant to penicillin-G and ampicillin. About 89%, 26%, 21% and 11% of the bacterial isolates were resistant to amoxicillin, co-trimoxazole, nalidixic acid and erythromycin, respectively. It was found that bacterial isolates produce chemical(s) inhibitory to other bacterial strains including both gram positive and gram negative bacteria. Further studies are needed to characterize the potential antibacterial factor(s) and other bioactive compound (s) present in these bacterial isolates from soil samples.

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Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of Bacteria with Biochemical and Pharmacological Importance from Soil Samples of Dhaka City

Begum

Mannan

Rezwan

et al. 2017

Dhaka Univ. J. Pharm. Sci

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“…The expression of cryptic gene clusters is conditioned and can be activated by genetic manipulations of essential genes (7,8). One of the approaches is to replace the native promoters of biosynthetic structural genes with constitutive promoters.…”

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confidence: 99%

Activation and mechanism of a cryptic oviedomycin gene cluster via the disruption of a global regulatory gene, adpA, in Streptomyces ansochromogenes

Zhang

Zhuo

et al. 2017

Journal of Biological Chemistry

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Genome sequencing analysis has revealed at least 35 clusters of likely biosynthetic genes for secondary metabolites in Disruption of encoding a global regulator (AdpA) resulted in the failure of nikkomycin production, whereas other antibacterial activities against ,, and were observed with the fermentation broth of ΔadpA but not with that of the wild-type strain. Transcriptional analysis showed that a cryptic gene cluster (), which shows high identity with an oviedomycin biosynthetic gene cluster (), was activated in ΔadpA. The corresponding product of was characterized as oviedomycin by MS and NMR spectroscopy. To understand the molecular mechanism of activation, the roles of six regulatory genes situated in the cluster were investigated. Among them, proteins encoded by co-transcribed genes and are positive regulators of AdpA directly represses the transcription of and Co-overexpression of and can relieve the repression of AdpA on transcription and effectively activate oviedomycin biosynthesis. The promoter of is identified as the direct target of OvmZ and OvmW. This is the first report that AdpA can simultaneously activate nikkomycin biosynthesis but repress oviedomycin biosynthesis in one strain. Our findings provide an effective strategy that is able to activate cryptic secondary metabolite gene clusters by genetic manipulation of global regulatory genes.

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“…Two Streptomyces strains, isolated from Dendroctonus frontalis beetles, inhibit the antagonistic Ophiostoma fungus, but not the mutualistic fungus Entomocorticium, suggesting a defensive role that supports the beetle-fungus mutualism. The molecules responsible for this selective antifungal activity are the polyketide mycangimycin [70] and the polycyclic tetramate macrolactams, frontalamides A and B [71,72].…”

Section: Symbiosis Relationshipsmentioning

confidence: 99%

“…Nonculturable microorganisms are, in fact, a majority, and they represent an important challenge in the screening for new secondary metabolites. Next generation sequencing (NGS) has revealed the big pharmacological potential of uncultured bacteria; hence, approaches to improve cultivation-based methods, such as isolation chip (iChip), which is a method of culturing bacteria within its soil environment, or co-cultures, culturing actinomycetes with other bacteria (generally species with which they naturally coexist), are being used successfully [70][71][72]. The combination of iChip and unexplored ecosystems or symbiotic relationships, mentioned above, is promising as well.…”

Section: Nonculturable Microorganismsmentioning

confidence: 99%

Streptomyces as a Source of Antimicrobials: Novel Approaches to Activate Cryptic Secondary Metabolite Pathways

Manteca¹,

Yagüe²

2019

Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods

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Streptomyces is the most important bacterial genus for bioactive compound production. These soil bacteria are characterized by a complex differentiation cycle. Streptomyces is extremely important in biotechnology, producing approximately two thirds of all antibiotics, as well as many compounds of medical and agricultural interest. Drug discovery from streptomycetes became challenging once the most common compounds were discovered, and the system was basically abandoned by industry. Simultaneously, antibiotic resistance is increasing dramatically, and new antibiotics are required. Screening from nature is being resumed (exploring new environments, looking for elicitors, metagenome, etc.). Secondary metabolism is conditioned by differentiation; although the relationship between both has long remained elusive, differentiation as a trigger for antibiotic production remains basically unexplored. Most cultures used in screening campaigns for new bioactive molecules have been performed empirically, and workflow was extremely productive during the so-called golden age of antibiotics; however, currently there is a bottleneck. Streptomyces is still the most important natural source of antibiotics, and it also harbors many cryptic secondary metabolite pathways not expressed under laboratory conditions. In this chapter, we review strategies based on differentiation, one of the keys improving secondary metabolite production and activating cryptic pathways to face the challenges of drug discovery.

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New approaches to antibiotic discovery

Cited by 62 publications

References 63 publications

Isolation and Characterization of Bacteria with Biochemical and Pharmacological Importance from Soil Samples of Dhaka City

Isolation and Characterization of Bacteria with Biochemical and Pharmacological Importance from Soil Samples of Dhaka City

Activation and mechanism of a cryptic oviedomycin gene cluster via the disruption of a global regulatory gene, adpA, in Streptomyces ansochromogenes

Streptomyces as a Source of Antimicrobials: Novel Approaches to Activate Cryptic Secondary Metabolite Pathways

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