Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues

Loza, Einars; Sarciaux, Matthieu; Ikaunieks, Martins; Katkevičs, Mārtiņš; Kukosha, Tatyana; Trufilkina, Nadezhda; Ryabova, Victoria; Shubin, Kirill; Pantel, Lucile; Serri, Marine; Huseby, Douglas L.; Cao, Sha; Yadav, Kavita; Hjort, Karin; Hughes, Diarmaid; Gualtieri, Maxime; Sūna, Edgars; Racine, Emilie

doi:10.1016/j.bmc.2020.115469

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…A medicinal chemistry program was started to optimize their pharmacological properties. NOSO-502, the first ODL preclinical candidate, was selected [ 157 ]. This compound is currently under preclinical development for the treatment of multidrug-resistant Gram-negative infections in hospitalized patients [ 155 ].…”

Section: A Discussion: Discoveries and Evaluationmentioning

confidence: 99%

Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)

Fodor

Gualtieri²,

Zeller

et al. 2022

Pathogens

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Antimicrobial multidrug resistance (MDR) is a global challenge, not only for public health, but also for sustainable agriculture. Antibiotics used in humans should be ruled out for use in veterinary or agricultural settings. Applying antimicrobial peptide (AMP) molecules, produced by soil-born organisms for protecting (soil-born) plants, seems a preferable alternative. The natural role of peptide-antimicrobials, produced by the prokaryotic partner of entomopathogenic-nematode/bacterium (EPN/EPB) symbiotic associations, is to sustain monoxenic conditions for the EPB in the gut of the semi-anabiotic infective dauer juvenile (IJ) EPN. They keep pathobiome conditions balanced for the EPN/EPB complex in polyxenic (soil, vanquished insect cadaver) niches. Xenorhabdus szentirmaii DSM16338(T) (EMC), and X. budapestensis DSM16342(T) (EMA), are the respective natural symbionts of EPN species Steinernema rarum and S. bicornutum. We identified and characterized both of these 15 years ago. The functional annotation of the draft genome of EMC revealed 71 genes encoding non-ribosomal peptide synthases, and polyketide synthases. The large spatial Xenorhabdus AMP (fabclavine), was discovered in EMA, and its biosynthetic pathway in EMC. The AMPs produced by EMA and EMC are promising candidates for controlling MDR prokaryotic and eukaryotic pathogens (bacteria, oomycetes, fungi, protozoa). EMC releases large quantity of iodinin (1,6-dihydroxyphenazine 5,10-dioxide) in a water-soluble form into the media, where it condenses to form spectacular water-insoluble, macroscopic crystals. This review evaluates the scientific impact of international research on EMA and EMC.

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Section: A Discussion: Discoveries and Evaluationmentioning

confidence: 99%

Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)

Fodor

Gualtieri²,

Zeller

et al. 2022

Pathogens

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“…Moreover, AMPS are often produced in prokaryote/eukaryote symbiotic associations where they bridge the innate and the adaptive immune system and provide optimal conditions for symbiosis. Efforts to maximize human benefits from AMPs antimicrobial activity include identification, quantitative structure/activity relation (QSAR) analysis of natural AMPs and derivatives (Loza et al, 2020 ), followed by designing, optimizing, synthesizing, and screening analogs (Fodor et al, 2020 ).…”

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confidence: 99%

Editorial: New Antimicrobial Peptides From Bacteria/Invertebrate Obligate Symbiotic Associations

et al. 2022

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“…ODL’s overall mechanism of action is to interfere with protein synthesis, and the pattern it works depends on the concentration of the drug. 104 Notably, its binding site is different from other inhibitors that target the 30S ribosomal subunit, and the mutations that render the mitochondrial ribosome susceptible to aminoglycosides are not expected to affect the binding or action of ODLs. 105 ODLs exhibit excellent broad-spectrum antimicrobial activity against a broad range of GNB and GPB ( K. pneumoniae, E. coli, Enterobacter aerogenes, E. cloacae, Proteus mirabilis, S. aureus, and Enterococcus faecalis ), including drug-resistant strains that are difficult to treat, such as carbapenemase-producing Enterobacterales.…”

Section: Progress In Research and Development Of Drugs Against Drug-resistant Bacteriamentioning

confidence: 99%

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

Cui¹,

Lü²,

Yue³

2021

IDR

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Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health and attracted the attention of the World Health Organization (WHO) and the governments of various countries. Therefore, the establishment of measures against bacterial resistance and the discovery of new antibacterial drugs are increasingly urgent to better contain the emergence of bacterial resistance and provide a reference for the development of new antibacterial drugs. In this review, we discuss some antibiotic drugs that have been approved for clinical use and a partial summary of the meaningful research results of anti-drug resistant bacterial drugs in different fields, including the antibiotic drugs approved by the FDA from 2015 to 2020, the potential drugs against drug-resistant bacteria, the new molecules synthesized by chemical modification, combination therapy, drug repurposing, immunotherapy and other therapies.

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Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues

Cited by 6 publications

References 36 publications

Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)

Type Strains of Entomopathogenic Nematode-Symbiotic Bacterium Species, Xenorhabdus szentirmaii (EMC) and X. budapestensis (EMA), Are Exceptional Sources of Non-Ribosomal Templated, Large-Target-Spectral, Thermotolerant-Antimicrobial Peptides (by Both), and Iodinin (by EMC)

Editorial: New Antimicrobial Peptides From Bacteria/Invertebrate Obligate Symbiotic Associations

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

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