Treatment-Resistant Syphilis

Beckh, Walter; Kulchar, George V.

doi:10.1001/archderm.1939.01490010004001

Cited by 8 publications

(4 citation statements)

References 7 publications

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“…The sequence analysis revealed that the cluster organisation is similar to the BGC of nystatin [313]. The polyketide chain is biosynthesised by an assembly line involving one loading (encoded by amphA) and 18 Nourse. Later, the strain was renamed S. noursei and the compound name changed from fungicidin to nystatin [157].…”

Section: Amphotericin Bmentioning

confidence: 95%

“…Finally, Based on the success of antimicrobial drugs during the "Golden Age" of antibiotic discovery (1940s-1960s) some experts were confident that "the tide had turned" in the war against pathogens causing severe infections. However, microbes develop the ability to resist the effects of an antibiotic whenever the dose of the drug is too low to eliminate the whole population of the pathogen (minimum bactericidal concentration (MBC)) and thus, antibiotic resistance developed shortly after the drugs were applied [18][19][20][21][22][23][24]. Resistance to antibiotics arises from chromosomal mutations or acquisition of genetic elements encoding resistance genes (horizontal gene transfer).…”

Section: The Biosynthetic Assembly Linesmentioning

confidence: 99%

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Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

Robertsen

Musiol-Kroll

2019

Antibiotics

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Actinomycetes are remarkable producers of compounds essential for human and veterinary medicine as well as for agriculture. The genomes of those microorganisms possess several sets of genes (biosynthetic gene cluster (BGC)) encoding pathways for the production of the valuable secondary metabolites. A significant proportion of the identified BGCs in actinomycetes encode pathways for the biosynthesis of polyketide compounds, nonribosomal peptides, or hybrid products resulting from the combination of both polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The potency of these molecules, in terms of bioactivity, was recognized in the 1940s, and started the “Golden Age” of antimicrobial drug discovery. Since then, several valuable polyketide drugs, such as erythromycin A, tylosin, monensin A, rifamycin, tetracyclines, amphotericin B, and many others were isolated from actinomycetes. This review covers the most relevant actinomycetes-derived polyketide drugs with antimicrobial activity, including anti-fungal agents. We provide an overview of the source of the compounds, structure of the molecules, the biosynthetic principle, bioactivity and mechanisms of action, and the current stage of development. This review emphasizes the importance of actinomycetes-derived antimicrobial polyketides and should serve as a “lexicon”, not only to scientists from the Natural Products field, but also to clinicians and others interested in this topic.

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Section: Amphotericin Bmentioning

confidence: 95%

Section: The Biosynthetic Assembly Linesmentioning

confidence: 99%

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

Robertsen

Musiol-Kroll

2019

Antibiotics

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“…Antimicrobial compounds produced were by microbes to outcompete rivalry or defence mechanisms against microbes (Davies and Davies, 2010) , (Beckh and Kulchar, 1939). The evolution of the resistance mechanisms helped the other microbes to withstand the stress (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Next-Generation Approaches Needed to Tackle Antimicrobial Resistance for the Development of Novel Therapies Against the Deadly Pathogens

Bhandari

Suresh

2022

Front. Pharmacol.

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The advent of antimicrobials was a miracle that saved millions of lives across the globe. With the discovery of penicillin, varieties of other antimicrobials came into play one after another. However, the injudicious use of antimicrobials for therapeutics and prophylactics and overuse in agriculture and animal husbandry industries resulted in its gloominess and rise of antimicrobial resistance. The microbes have slowly outsmarted the human race with diverse mechanisms to evade the antimicrobial effects of the drugs in use. The review aims to discuss the emergence of resistance in bacterial species with time and the various means by which bacterial cells had safeguarded themselves. In addition to that, we have also highlighted new approaches currently used to tackle antimicrobial resistance or practices that could be useful in identifying new treatment options.

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“…As early as 1924, predating the discovery of penicillin, antimicrobial resistance was reported against the antimicrobial such as Salvarsan, introduced in 1910 for the treatment of syphilis [5,6]. Many other reports on the resistance towards Salvarsan soon followed [7,8]. Similarly, 50% of Staphylococcus aureus infections in Britain were reported to be resistant to penicillin by 1949, only five years after its introduction to the market in 1944 [9].…”

Section: Introductionmentioning

confidence: 99%

Direct Detection of Antibacterial-Producing Soil Isolates Utilizing a Novel High-Throughput Screening Assay

Laubscher

Rautenbach

2022

Microorganisms

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The ever-increasing global threat of common infections developing resistance to current therapeutics is rapidly accelerating the onset of a primitive post-antibiotic era in medicine. The prevention of further antimicrobial resistance development is unlikely due to the continued misuse of antibiotics, augmented by the lack of discovery of novel antibiotics. Screening large libraries of synthetic compounds have yet to offer effective replacements for current antibiotics. Due to historical successes, discovery from large and diverse natural sources and, more specifically, environmental bacteria, may still yield novel alternative antibiotics. However, the process of antibiotic discovery from natural sources is laborious and time-consuming as a result of outdated methodologies. Therefore, we have developed a simple and rapid preliminary screening assay to identify antibacterial-producing bacteria from natural sources. In brief, the assay utilizes the presence or absence of luminescence in bioluminescent reporter bacteria and test bacterium co-cultures in a 96-well plate format to determine the absence or presence of antibacterial compound production. Our assay, called the bioluminescent simultaneous antagonism (BSLA) assay, can accurately distinguish between known antibacterial-producing and non-producing test bacteria. The BSLA assay was validated by screening 264 unknown soil isolates which resulted in the identification of 10 antibacterial-producing isolates, effectively decreasing the pool of isolates for downstream analysis by 96%. By design, the assay is simple and requires only general laboratory equipment; however, we have shown that the assay can be scaled to automated high-throughput screening systems. Taken together, the BSLA assay allows for the rapid pre-screening of unknown bacterial isolates which, when coupled with innovative downstream dereplication and identification technologies, can effectively fast-track antimicrobial discovery.

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Treatment-Resistant Syphilis

Cited by 8 publications

References 7 publications

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

Next-Generation Approaches Needed to Tackle Antimicrobial Resistance for the Development of Novel Therapies Against the Deadly Pathogens

Direct Detection of Antibacterial-Producing Soil Isolates Utilizing a Novel High-Throughput Screening Assay

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