{"id":7087,"date":"2016-10-05T11:19:36","date_gmt":"2016-10-05T17:19:36","guid":{"rendered":"http:\/\/canadianglycomics.ca\/?p=7087"},"modified":"2019-07-31T16:08:49","modified_gmt":"2019-07-31T22:08:49","slug":"hybrid-antibiotic-created-with-molecular-rope-kills-resistant-bacteria","status":"publish","type":"post","link":"https:\/\/canadianglycomics.ca\/fr\/hybrid-antibiotic-created-with-molecular-rope-kills-resistant-bacteria\/","title":{"rendered":"Hybrid Antibiotic Created With Molecular ‘Rope’ Kills Resistant Bacteria"},"content":{"rendered":"
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By Alex Berezow<\/a><\/span><\/em><\/div>\n<\/div>\n<\/div>\n<\/div>\n
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Due to increasing antibiotic resistance, microbiologists are on the lookout for unconventional ways to kill bacteria. Atypical\u00a0methods range from phage<\/a> therapy<\/a>, in which bacteria-killing viruses are unleashed upon the microbes, to the use of “bed-of-nails” surfaces<\/a> that physically rip bacteria apart.<\/p>\n

Such out-of-the-box thinking was displayed yet again by a team of scientists from the University of Manitoba [including two GlycoNet scientists\u00a0Drs. George Zhanel and Frank Schweizer]<\/strong> who created a hybrid\u00a0antibiotic by tying together two different antibiotics with a molecular “rope.”<\/p>\n

One strategy to fight\u00a0resistance is to hit a bacterium with multiple antibiotics at the same time. The reasoning is that, while it is relatively simple for a bacterium to spontaneously mutate to avoid the lethal effect of one antibiotic, it is very\u00a0unlikely that multiple\u00a0mutations will occur simultaneously that protect it against more than one. In other words, a bacterium may\u00a0become resistant to antibiotic A or\u00a0antibiotic B if they are used separately; but if used together, antibiotics A + B present a formidable challenge to resistance.<\/p>\n

To create their hybrid, the researchers subjected the antibiotic tobramycin to a series of chemical reactions that (1) attached a molecular “rope” (a chain of 12 carbon atoms)\u00a0to the center of the molecule and (2) tied the rope to a second antibiotic, moxifloxacin. (See diagram\u00a0at the top of this article.)<\/p>\n

Then, they tested how the hybrid antibiotic performed against clinically isolated samples of Pseudomonas aeruginosa<\/em>, a bacterium that is both highly resistant to multiple antibiotics and is commonly transmitted in hospitals. (See below.)<\/p>\n

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Susceptibility to antibiotics is measured using the minimum inhibitory concentration\u00a0(MIC, measured in micrograms per milliliter), which indicates the lowest amount of antibiotic necessary to prevent the bacteria\u00a0from growing. (Thus, the higher the number, the more resistant the bacteria\u00a0are\u00a0to that antibiotic.)<\/p>\n

Note that\u00a0most clinical isolates of P. aeruginosa<\/em> were highly\u00a0resistant to both moxifloxacin (red box) and tobramycin (blue box)\u00a0but that the hybrid antibiotic (purple box) was quite effective at inhibiting bacterial growth. The authors inferred that whatever molecular mechanisms allow\u00a0these bacteria to be resistant to each antibiotic individually do\u00a0not apply to the hybrid antibiotic.<\/p>\n

So the team was curious to discover\u00a0how exactly their hybrid antibiotic worked. Their investigation suggested that it operated in a completely different way than the original antibiotics. Instead of blocking protein synthesis (like tobramycin) or inhibiting DNA replication (like moxifloxacin), the\u00a0hybrid exhibited\u00a0an entirely new mode of action: It pokes\u00a0holes in a\u00a0bacterium’s\u00a0outer membrane and disrupts the electrical field potential (called the proton motive force<\/em>)\u00a0associated with the inner membrane. The former causes the bacterium to literally disintegrate (see below), and the latter disrupts various aspects of bacterial physiology.<\/p>\n

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Additionally, the hybrid antibiotic rescued moths infected with P. aeruginosa<\/em>.\u00a0Even better, when the authors tried to coax\u00a0P. aeruginosa<\/em>\u00a0into becoming resistant to their hybrid antibiotic, they were unable to. This bizarre molecule, at least\u00a0for the time being, is too much for this\u00a0microbe\u00a0to handle.<\/p>\n

Citation<\/a>:\u00a0Bala Kishan Gorityala et al. “Hybrid Antibiotic Overcomes Resistance in P. aeruginosa<\/em> by Enhancing Outer Membrane Penetration and Reducing Efflux.”\u00a0J\u00a0Med\u00a0Chem<\/em>\u00a059 (18):\u00a08441\u20138455.\u00a0Published:\u00a013-Aug-2016.\u00a0DOI: 10.1021\/acs.jmedchem.6b00867<\/p>\n

The article is republished from University of Manitoba UM Today<\/a>.<\/p>\n

About the Author:<\/strong><\/p>\n

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\"alex-berezow\"Dr. Alex Berezow<\/a>\u00a0joined the American Council on Science and Health as Senior Fellow of Biomedical Science in May 2016. He is a prolific science journalist whose work regularly appears in BBC News,\u00a0The Economist<\/em>, and\u00a0USA Today<\/em>, where he serves as a member of the Board of Contributors. With Hank Campbell in 2012, he co-authored the book\u00a0Science Left Behind<\/em>, which was an environmental policy bestseller. Formerly, he was the founding editor of RealClearScience. He holds a Ph.D. in microbiology.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

A team of scientists from the University of Manitoba created a hybrid\u00a0antibiotic by tying together two different antibiotics with a molecular “rope.”<\/p>","protected":false},"author":2,"featured_media":11639,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[203],"tags":[34,35,36,12,37,38,39,40],"class_list":["post-7087","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-highlight","tag-antibiotic-resistance","tag-antibiotics","tag-antimicrobials","tag-bacteria","tag-membrane-penetration","tag-molecular-rope","tag-p-aeruginosa","tag-reducing-efflux","wpbf-post"],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t