{"id":1023,"date":"2019-10-21T10:07:30","date_gmt":"2019-10-21T10:07:30","guid":{"rendered":"http:\/\/horizon.peachpuff-wolverine-566518.hostingersite.com\/?p=1023"},"modified":"2019-10-21T10:07:30","modified_gmt":"2019-10-21T10:07:30","slug":"can-we-reverse-antibiotic-resistance","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/horizon\/1023\/can-we-reverse-antibiotic-resistance\/","title":{"rendered":"Can we reverse antibiotic resistance?"},"content":{"rendered":"
<\/div>\n
by Vittoria D’Alessio<\/div>\n

In the battle against antibiotic resistance, some scientists are trying a new approach: re-sensitising bacteria to drugs they no longer respond to so that existing antibiotics can hit their target once more.<\/strong><\/h3>\n
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\u2018This is a sustainable and straightforward approach to the problem of antibiotic resistance,\u2019 said Fredrik Almqvist, professor of organic chemistry at Ume\u00e5 University in Sweden. \u2018New antibiotics take a huge amount of money to develop. We are developing compounds that boost the antibiotics we already have, which is much more cost effective.\u2019<\/p>\n

These new compounds don\u2019t kill bacteria. Instead, they selectively disarm them, giving antibiotics the chance to swoop in and finish the job. \u2018They sensitise the pathogen and restore the effectiveness of antibiotics,\u2019 said Prof. Almqvist.\u00a0\u2018It\u2019s amazingly cool.\u2019<\/p>\n

Much of Prof. Almqvist\u2019s research is focused on tuberculosis, an infection that\u00a0kills 1.6 million people every year<\/a>. Some strains of the disease, such as\u00a0Mycobacteria tuberculosis<\/em>\u00a0(Mtb), show formidable resistance to antibiotics, making them particularly difficult to treat.<\/p>\n

However, Prof. Almqvist has joined forces with molecular biologist Christina Stallings\u00a0at Washington University, US, to develop\u00a0chemical compounds<\/a>\u00a0that break down the defences of these drug-resistant strains by inhibiting the formation of biofilm \u2013 a matrix of molecules that surrounds bacterial cells, providing protection against outside assaults. Enclosed in biofilm, bacteria can be up to\u00a01,000-fold more resistant<\/a>\u00a0to antibiotics, but in the presence of Prof. Almqvist\u2019s compounds, drug-resistant TB bacteria are rendered defenceless.<\/p>\n

\u2018The tuberculosis bacteria are there and alive, but they don\u2019t form a biofilm,\u2019 said Prof. Almqvist. \u2018With no biofilm, they get killed by the antibiotic.\u2019<\/p>\n

Prof. Almqvist says the compounds discovered in his lab \u2013 known as Mycobacterial Tolerance Inhibitors (MTIs) \u2013 show promise in two ways: they block Mtb\u2019s defences against antibiotics, and they reduce treatment times for all TB patients from 6-9 months to just one month. His biochemical company, Quretech Bio, is now ready to start testing Mtb compounds on animal models.<\/p>\n

Antibiotic-resistance breakers<\/strong><\/p>\n

Superbugs\u00a0Methicillin-resistant Staphylococcus aureus<\/em>\u00a0(MRSA) and\u00a0Vancomycin-resistant Enterococci (<\/em>VRE) have also had their antibiotic resistance reversed in Prof Almqvist\u2019s lab after exposure to antibiotic-resistance breakers (ARBs).<\/p>\n

\u2018These are infections that can move to a very dramatic situation within hours if they are not treated effectively,\u2019 said Prof. Almqvist.<\/p>\n

He explains that ARBs could bring life-threatening infections under control by restoring the potency of antibiotics that have lost their edge. \u2018We see this as a straightforward approach to a really big problem,\u2019 he said.<\/p>\n

As part of a project called\u00a0QTB4AMR<\/a>, he is developing a methodology for synthesising compounds that can then be tested and developed into ARBs. Compounds (some structurally similar to one another) are being evaluated for their ability to \u2018strongly synergise\u2019 with existing antibiotics at a rate of 100 to 500 new compounds per year.<\/p>\n

\u2018We hope to motivate further development,\u2019 said Prof. Almqvist, admitting that it will take \u2018a lot of investment\u2019 and \u2018big engagement\u2019 from both academic research bodies and pharmaceutical companies before his ARBs yield new treatments for patients.<\/p>\n

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\"Scientists
Scientists are developing compounds that re-sensitise the TB bacterium to antibiotics by breaking down its defensive biofilm. Mycobacterium tuberculosis. Image credit – Flickr\/NIAID, licensed under CC BY 2.0<\/figcaption><\/figure>\n<\/div>\n

To an extent, antibiotic resistance is a naturally occurring phenomenon. Bacteria mutate rapidly, and mutant strains that are able to survive a dose of antibiotics have an immediate evolutionary advantage. But our misuse and overuse of antibiotics is accelerating the process of resistance, putting us in a race to stay ahead of the superbugs.\u00a0Resistance is a global catastrophe<\/a>\u00a0that kills 700,000 people every year. If solutions are not found fast, drug resistance is expected to cause\u00a0300 million premature deaths<\/a>\u00a0globally over the next 35 years.<\/p>\n

Research aimed at finding new antibiotics has virtually stalled over the past 30 years. Of the products being tested today, only a handful are classed by the World Health Organisation (WHO) as\u00a0innovative treatments<\/a>\u00a0with new modes of action that will add value to the arsenal of existing treatments (as opposed to reformulations of existing drugs). Most alarmingly,\u00a0none of the new antibiotics in development<\/a>\u00a0are expected to be effective against the most dangerous forms of antibiotic-resistant bacteria.<\/p>\n

Cost<\/strong><\/p>\n

So, why the lack of innovation? Engineering a new formulation is an\u00a0expensive business<\/a>, yet there\u2019s pressure on doctors from health organisations around the world to prescribe antibiotics prudently. In other words, the world needs drugs that can sit on the shelf until they are absolutely essential \u2013 hardly an incentive for drug firms to invest billions in research (indeed, between 2003 and 2013,\u00a0less than 5% of venture capital investment<\/a>\u00a0in pharmaceutical R&D was for antimicrobial development). What\u2019s more, unlike many other life-saving medicines, antibiotics are generally used short-term and patients expect to pick them up cheaply.<\/p>\n

\u2018We pay millions of euros for some therapies, but we expect antibiotics \u2013 which are life-saving drugs \u2013 to cost just a few euros,\u2019 said Mariana Pinho, head of the bacterial cell biology laboratory at the Universidade Nova de Lisboa\u00a0in Portugal.<\/p>\n

She added: \u2018This is why the idea of taking drugs that have already been approved for clinical use and repurposing them is very attractive. Re-sensitising bacteria is far more cost effective than developing new antibiotics.\u2019<\/p>\n

Like Prof. Almqvist, Prof. Pinho is on a quest to find ways to boost the performance of existing antibacterial medications. Though she stresses that the hunt for new antibiotics must never cease, she also believes in the potential of combination therapies, where washed-out antibiotics are\u00a0restored\u00a0<\/a>to full working order after being blended with smart-acting new compounds.<\/p>\n

Her\u00a0ChronosAntibiotic project<\/a>\u00a0centres around\u00a0Staphylococcus aureus<\/em>, one of the most common multidrug-resistant bacterium in Europe.\u00a0Staphylococcus aureus<\/em>\u00a0causes a raft of conditions, some of them serious, collectively known as staph infections.<\/p>\n

Using super-resolution microscopy, she studies\u00a0the mechanisms of the bacteria\u2019s cell division<\/a>, looking for moments in the cell cycle when the microbe is more susceptible to the actions of antibiotics. She believes that the addition of targeted resistance-busting compounds will allow antibiotics to use these windows of opportunity to best effect.<\/p>\n

\u2018We want to find those weak points in the cell cycle,\u2019 she said. \u2018These are our long-term aims.\u2019<\/p>\n

Prof. Pinho is part of the team that has found a chink in the armour of MRSA drug resistance. A small molecule called\u00a0DNAC-1<\/a>, discovered by Prof. Pinho\u2019s collaborators, has been seen to intensify the effect of the antibiotic oxacillin by damaging the microbe\u2019s cell membrane. With the membrane disrupted, the antibiotic is free to stream in and kill the cell.<\/p>\n

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‘We see this as a straightforward approach to a really big problem.’<\/p>\n

Prof. Fredrik Almqvist, Ume\u00e5 University, Sweden<\/p>\n<\/blockquote>\n<\/div>\n

The cell membrane is just one of the potential targets for the action of new compounds. All cellular components and metabolic actions are coming under careful scrutiny for their susceptibility to damage and disruption.<\/p>\n

To keep track of her lab\u2019s findings, Prof. Pinho is building a library that pairs bacterial genes known as reporters with compounds that are found to inhibit the expression of these genes, thereby leaving the cell sensitive to antibiotics.<\/p>\n

Her initial aim is to deepen the research community\u2019s understanding of the cellular pathways that lead to drug resistance. \u2018Just understanding the biology is an important start,\u2019 she said.<\/p>\n

By 2023, she hopes to have discovered reporters that are useful for antibiotics discovery to turn into a new drug or a smart compound to resurrect an existing one.<\/p>\n

\u2018I would be very happy if, during the course of my life, I could contribute to the development of a new drug,\u2019 she said.<\/p>\n

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Four bacterial defences against antibiotics<\/h3>\n

1. Invisibility cloak<\/strong><\/p>\n

The bacterial organism changes its physiology so that the antibiotic cannot find its target. Some bacteria will actively alter their cell wall structure to make it invisible.<\/p>\n

2. Pump and flush<\/strong><\/p>\n

Bacteria regularly expel harmful compounds from their system using a protein to pump it out of the cell. These efflux pumps have evolved to now actively flush out antibiotics.<\/p>\n

3. Protein shield<\/strong><\/p>\n

Proteins in the bacteria attach themselves to either antibiotics or the drug\u2019s target within the bacterial cell. That protein then prevents the antibiotic from successfully binding to its target.<\/p>\n

4. Counterattack<\/strong><\/p>\n

Some bacteria have evolved to produce defensive enzymes. They produce enzymes that either destroy or modify the antibiotic molecule and render them completely\u00a0ineffective<\/a>.<\/p>\n<\/div>\n

The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.<\/em><\/p>\n

Originally published on Horizon<\/a>.\u00a0<\/em><\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

by Vittoria D’Alessio In the battle against antibiotic resistance, some scientists are trying a new approach: re-sensitising bacteria to drugs they no longer respond to so that existing antibiotics can hit their target once more. \u2018This is a sustainable and straightforward approach to the problem of antibiotic resistance,\u2019 said Fredrik Almqvist, professor of organic chemistry … Read more<\/a><\/p>\n","protected":false},"author":298,"featured_media":1024,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"generate_page_header":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false},"categories":[12],"tags":[313,37,95,79,24,318],"class_list":["post-1023","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","tag-antibiotic-resistance","tag-health","tag-medicine","tag-research","tag-science","tag-superbugs"],"yoast_head":"\nCan we reverse antibiotic resistance? - Horizon Magazine Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/horizon\/1023\/can-we-reverse-antibiotic-resistance\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Can we reverse antibiotic resistance?\" \/>\n<meta property=\"og:description\" content=\"by Vittoria D’Alessio In the battle against antibiotic resistance, some scientists are trying a new approach: re-sensitising bacteria to drugs they no longer respond to so that existing antibiotics can hit their target once more. \u2018This is a sustainable and straightforward approach to the problem of antibiotic resistance,\u2019 said Fredrik Almqvist, professor of organic chemistry ... 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By working on new antibiotics or finding ways to revive existing ones in our medical arsenal, scientists aim to avoid a return to a world where even everyday infections may mean death.\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/scienceblog.com\/horizon\/category\/health\/"},"img":{"alt_text":"Image credit - Flickr\/ Sheep purple, licensed under CC BY 2.0","src":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=1050%2C600&ssl=1 3x, https:\/\/i0.wp.com\/scienceblog.com\/horizon\/wp-content\/uploads\/sites\/4\/2019\/10\/3060243118_992e36386c_k.jpg?resize=1400%2C800&ssl=1 4x"},"classes":[]},{"id":1029,"url":"https:\/\/scienceblog.com\/horizon\/1029\/sewage-rivers-and-soils-provide-missing-link-in-antibiotic-resistance-story\/","url_meta":{"origin":1023,"position":2},"title":"Sewage, rivers and soils provide missing link in antibiotic resistance story","author":"Horizon Magazine","date":"October 28, 2019","format":false,"excerpt":"If you think that the key to beating antibiotic resistance is only for doctors to prescribe less and scientists to find new drug candidates, you are probably wrong. 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