New antibiotic structures from fermentations

Singh, Sheo B.; Young, Katherine

doi:10.1517/13543776.2010.509347

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…Platensimycin is a bacteriostatic drug that does not exhibit cross-resistance to Gram-positive bacteria with MIC values of 0.1–0.32 mg/mL, therefore making it a potentially useful antibiotic candidate 130,131. Platensimycin was efficiently used in a murine model of a common S. aureus infection and no toxicity was observed in these animals.…”

Section: Platensimycin and Platencinmentioning

confidence: 99%

The use of platensimycin and platencin to fight antibiotic resistance

Allahverdiyev¹,

Bağırova²,

Abamor³

et al. 2013

IDR

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Infectious diseases are known as one of the most life-threatening disabilities worldwide. Approximately 13 million deaths related to infectious diseases are reported each year. The only way to combat infectious diseases is by chemotherapy using antimicrobial agents and antibiotics. However, due to uncontrolled and unnecessary use of antibiotics in particular, surviving bacteria have evolved resistance against several antibiotics. Emergence of multidrug resistance in bacteria over the past several decades has resulted in one of the most important clinical health problems in modern medicine. For instance, approximately 440,000 new cases of multidrug-resistant tuberculosis are reported every year leading to the deaths of 150,000 people worldwide. Management of multidrug resistance requires understanding its molecular basis and the evolution and dissemination of resistance; development of new antibiotic compounds in place of traditional antibiotics; and innovative strategies for extending the life of antibiotic molecules. Researchers have begun to develop new antimicrobials for overcoming this important problem. Recently, platensimycin – isolated from extracts of Streptomyces platensis – and its analog platencin have been defined as promising agents for fighting multidrug resistance. In vitro and in vivo studies have shown that these new antimicrobials have great potential to inhibit methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in bacteria. Showing strong efficacy without any observed in vivo toxicity increases the significance of these antimicrobial agents for their use in humans. However, at the present time, clinical trials are insufficient and require more research. The strong antibacterial efficacies of platensimycin and platencin may be established in clinical trials and their use in humans for coping with multidrug resistance may be allowed in the foreseeable future.

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Section: Platensimycin and Platencinmentioning

confidence: 99%

The use of platensimycin and platencin to fight antibiotic resistance

Allahverdiyev¹,

Bağırova²,

Abamor³

et al. 2013

IDR

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“…4,6 It has minimal inhibitory (MIC) values of 0.1-0.32 mg ml À1 against Gram-positive bacteria. 7 Furthermore, it is relatively non-toxic to humans. Its unique target is bacterial fatty acid synthesis (FAS).…”

Section: Platensimycinmentioning

confidence: 99%

“…On the other hand, platencin exhibited a 27-fold higher activity over platensimycin against FabH. 7 X-ray crystallographic studies have revealed that the formation of the acyl-FabF intermediate further exposes the enzyme's active site by allowing ACP to be released. 9,22 The acyl-enzyme intermediate must form before platensimycin can interact with the malonyl-binding site of FabF.…”

Section: Mode Of Actionmentioning

confidence: 99%

Platensimycin and platencin: promising antibiotics for future application in human medicine

Martens

Demain

2011

J Antibiot

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Platensimycin and platencin are novel antibiotics produced by Streptomyces platensis. They are potent and non-toxic natural products active against Gram-positive pathogens, including antibiotic-resistant strains and Mycobacterium tuberculosis. They were isolated using an intriguing target-based whole-cell antisense differential sensitivity assay as inhibitors of fatty acid biosynthesis of type II. This type of biosynthesis is not present in humans. Platensimycin inhibits the elongation-condensing enzyme FabF, whereas platencin inhibits both FabF and FabH. For these antibiotics to become successful drugs, their pharmacokinetics must be improved. They have too high a rate of clearance in the body, yielding a low degree of systematic exposure. They work well when administered by continuous infusion, but this is not a useful method of delivery to patients. The two antibiotics and many analogs have been prepared by chemical synthesis. Natural congeners have also been obtained from the producing actinomycete. However, none of these molecules are as active as platensimycin and platencin. Using tools of rational metabolic engineering, superior strains have been produced making hundreds of times more antibiotic than the natural strains.

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“…In addition to their activity against resistant pathogens (MRSA and VRE), both antibiotics exhibit potent antibacterial activity (MIC = 0.06–2 μg ml −1 ) against Gram-positive pathogens, 7 including penicillin-resistant Streptococcus pneumoniae . 8 They have also shown activity against mycobacteria such as Mycobacterium tuberculosis , Mycobacterium bovis , and Mycobacterium smegmatis .…”

Section: Introductionmentioning

confidence: 99%

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid

et al. 2017

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Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only L-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.

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New antibiotic structures from fermentations

Abstract: Natural products continue to play significant role in the discovery of new antibiotics and clearly a renewed interest in the natural products discovery is warranted to discover novel antibiotics to fight drug resistant bacteria.

Cited by 12 publications

References 25 publications

The use of platensimycin and platencin to fight antibiotic resistance

The use of platensimycin and platencin to fight antibiotic resistance

Platensimycin and platencin: promising antibiotics for future application in human medicine

Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of l-aspartic acid

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