{"id":20168,"date":"2023-09-14T10:28:12","date_gmt":"2023-09-14T10:28:12","guid":{"rendered":"https:\/\/clinlabint.com\/?p=20168"},"modified":"2023-09-14T10:28:12","modified_gmt":"2023-09-14T10:28:12","slug":"new-antibiotic-from-microbial-dark-matter-could-be-powerful-killer-of-superbugs","status":"publish","type":"post","link":"https:\/\/clinlabint.com\/new-antibiotic-from-microbial-dark-matter-could-be-powerful-killer-of-superbugs\/","title":{"rendered":"New antibiotic from microbial \u2018dark matter\u2019 could be powerful killer of superbugs"},"content":{"rendered":"
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\r\n\"Bio-Rad<\/a>\r\n<\/p>\n<\/div><\/section><\/div>

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New antibiotic from microbial \u2018dark matter\u2019 could be powerful killer of superbugs<\/h1>\/ in E-News<\/a> <\/span><\/span><\/header>\n<\/div><\/section>
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A powerful new antibiotic, isolated from bacteria that could not be studied before, seems capable of combatting harmful bacteria and multi-drug resistant \u2018superbugs\u2019. Named Clovibactin, the antibiotic appears to kill bacteria in an unusual way, making it more difficult for bacteria to develop resistance against it.<\/strong><\/h3>\n

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\u201cClovibactin is different,\u201d says Dr Markus Weingarth, a researcher from the Chemistry Department of Utrecht University. \u201cSince Clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance.\u201d<\/p>\n

Researchers from Utrecht University, Bonn University (Germany), the German Center for Infection Research\u00a0(DZIF), Northeastern University of Boston (USA), and the company NovoBiotic Pharmaceuticals (Cambridge, USA) have shared the discovery of Clovibactin and its killing mechanism in the journal\u00a0Cell. [1]<\/p>\n

Urgent need for new antibiotics<\/strong>
\nAntimicrobial resistance is a major problem for human health and researchers worldwide are looking for new solutions. \u201cWe urgently need new antibiotics to combat bacteria that become increasingly resistant to most clinically used antibiotics,\u201d says Dr Weingarth.<\/p>\n

However, the discovery of new antibiotics is a challenge: few new antibiotics have been introduced into the clinics over the past few decades.<\/p>\n

Bacterial dark matter<\/strong>
\nClovibactin was discovered by NovoBiotic Pharmaceuticals, a small US-based early-stage company, and microbiologist Prof. Kim Lewis from Northeastern University, Boston. Earlier, they developed a device that enables the growth of \u2018bacterial dark matter\u2019, so-called unculturable bacteria. Intriguingly, 99% of all bacteria are \u2018unculturable\u2019 and could not be grown in laboratories previously, hence they could not be mined for novel antibiotics. Using the device, called iCHip, the US researchers discovered Clovibactin in a bacterium isolated from sandy soil from North Carolina:\u00a0E. terrae ssp. Carolina.<\/p>\n

In the joint Cell publication, NovoBiotic Pharmaceuticals shows that Clovibactin successfully attacks a broad spectrum of bacterial pathogens. It was also successfully used to treat mice infected with the superbug\u00a0Staphylococcus aureus.<\/p>\n<\/div><\/section>
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Clovibactin molecular structure<\/em><\/p>\n<\/div><\/section>
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Unusual killing mechanism<\/strong>
\nClovibactin appears to have an unusual killing mechanism. It targets not just one, but three different precursor molecules that are all essential for the construction of the cell wall housing the bacteria. This was discovered by the group of Prof. Tanja Schneider from the University of Bonn in Germany, one of the\u00a0Cell\u00a0paper\u2019s co-authors.<\/p>\n

Prof. Schneider notes: \u201cThe multi-target attack mechanism of Clovibactin blocks bacterial cell wall synthesis simultaneously at different positions. This improves the drug\u2019s activity and substantially increases its robustness to resistance development.\u201d<\/p>\n

No resistance<\/strong>
\nHow exactly Clovibactin blocks the synthesis of the bacterial cell wall was revealed by the team of Dr Weingarth from Utrecht University. They used a special technique called solid-state nuclear magnetic resonance (NMR) that enabled them to study Clovibactin\u2019s mechanism under similar conditions as in bacteria.<\/p>\n

\u201cClovibactin wraps around the pyrophosphate like a tightly fitting glove. Like a cage that encloses its target\u201d says Dr Weingarth. This
\nis where Clovibactin gets its name, which is derived from Greek word \u201cKlouvi\u201d, which means cage. The remarkable aspect of Clovibactin\u2019s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it ignores that variable sugar-peptide part of the targets.<\/p>\n

\u201cAs Clovibactin only binds to the immutable, conserved part of its targets, bacteria will have a much harder time developing any resistance against it. In fact, we did not observe any resistance to Clovibactin in our studies.\u201d<\/p>\n

Fibrils capture the targets<\/strong>
\nClovibactin can do even more. Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.<\/p>\n

\u201cSince these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why Clovibactin selectively damages bacterial cells but is not toxic to human cells,\u201d says Dr Weingarth. \u201cClovibactin hence has potential for the design of improved therapeutics that kill bacterial pathogens without resistance development.\u201d<\/p>\n

Reference:<\/strong><\/em>
\n1. doi: https:\/\/doi.org\/10.1016\/j.cell.2023.07.038<\/a><\/em><\/p>\n<\/div><\/section>
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