{"id":77476,"date":"2022-09-30T13:24:13","date_gmt":"2022-09-30T11:24:13","guid":{"rendered":"https:\/\/www.pcb.ub.edu\/breaking-down-bacterias-protective-armor-to-overcome-antibiotic-resistance\/"},"modified":"2022-10-05T16:10:11","modified_gmt":"2022-10-05T14:10:11","slug":"breaking-down-bacterias-protective-armor-to-overcome-antibiotic-resistance","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/breaking-down-bacterias-protective-armor-to-overcome-antibiotic-resistance\/","title":{"rendered":"Breaking down bacteria\u2019s protective structure to overcome antibiotic resistance"},"content":{"rendered":"

A new triple-acting antibiotic agent has managed to break through the biofilm extracellular matrix \u2013 a protective structure built by bacteria \u2013 and eliminate more than 50% of the pathogens in one shot. The study, published in the scientific journal npj Biofilms and Microbiomes, was led by Eduard Torrents, group leader at the Institute for Bioengineering of Catalonia (IBEC)<\/a>, based in the Barcelona Science Park.<\/strong><\/p>\n

Persistent lung infections, chronic wounds, and healthcare-associated infections are typically much more difficult to treat than other types of bacterial infections. This is because they are often caused by biofilms \u2013 colonies of microbes, mainly bacteria, that grow together in a self-produced matrix that protects and isolate them from the external environment.<\/p>\n

This extracellular matrix exacerbates antibiotic resistance \u2014\u201cone of the biggest threats to global health\u201d, according to the World Health Organization\u2014 since it makes it up to 1000 times harder to kill the bacteria inside the biofilm. Biofilm infections are therefore the most important non-specific mechanism of antimicrobial resistance.<\/p>\n

Attacking these microbes with antibiotics alone is not enough. There is a need for tools that break down the extracellular matrix to access and kill the bacteria inside. A groundbreaking study published in the scientific journal npj Biofilms and Microbiomes, and led by IBEC, has achieved this.<\/p>\n

“By combining an antibiotic with a pair of biofilm-piercing agents, we built a drug that\u2019s far more potent than the antibiotic on its own \u2013 eliminating even the bacteria living inside the biofilm”, explains Eduard Torrents<\/strong>, chief researcher of this work.<\/p>\n

Torrents leads the\u00a0Bacterial infections: antimicrobial therapies<\/a>\u00a0group at IBEC and is an associate professor at the\u00a0University of Barcelona<\/a>. N\u00faria Blanco-Cabra<\/strong>, first-author of the scientific paper, is a postdoctoral researcher in Torrents\u2019 group at UB\/IBEC. The research was carried out in collaboration with scientists at\u00a0CIDETEC<\/a>\u00a0(Basque Country).<\/p>\n

Triple-acting drug combination<\/strong><\/h3>\n

In this study, the bacteria investigated was\u00a0Pseudomonas aeruginosa<\/em>. This pathogen commonly grows in biofilms in the lungs of patients with cystic fibrosis or chronic obstructive pulmonary disease (COPD), causing persistent infections. “We grew biofilm cultures in vitro<\/em>, using a technique that closely resembles the way they exist and grow in nature”, added Torrents<\/strong>. In clinical practice, these infections are usually treated with an antibiotic called tobramycin. However, its effectiveness is limited by its inability to penetrate the biofilm. This is because tobramycin, which is positively charged, is neutralized by the negatively charged extracellular matrix.<\/p>\n

\"\"
\nWith this in mind, the researchers loaded the antibiotic into negatively charged nanoparticle carriers. This had the effect of neutralizing the positive charge before the drug reached the biofilm, allowing it to break up the extracellular matrix and kill the bacteria inside. Crucially, these carriers \u2013 made from dextran-based single-chain nanoparticles \u2013 were able to carry up to 40% of the weight of the antibiotic. \u201cMany previously-studied nanocarriers have only been able to sustain a small load of the target compound, which has prevented their clinical use. We managed to overcome this hurdle\u201d, states Torrents<\/strong>.<\/p>\n

The antibiotic-loaded nanocarriers were also coated in an enzyme called DNase I. One of the \u201cglues\u201d that holds bacteria biofilms together is structural DNA found throughout the extracellular matrix. DNase I is able to break down this glue, causing the matrix to loosen, and allowing the antibiotic to even further penetrate the biofilm. By observing a series of time-lapse microscopy images, the researchers were able to verify that their agent had not only dissolved the structural DNA in the extracellular matrix, but also that it was acting on and killing the bacteria inside. With just one application, they reduced the bacterial biomass by more than half.<\/p>\n

New hope for \u201cuntreatable\u201d infections<\/strong><\/h3>\n

In clinical use, this agent would be administered in multiple doses, as is standard practice with antibiotics.”Having achieved such a significant clearance of the biofilm after just one dose of our agent, we predict that a full antibiotic course could considerably reduce the burden of these extremely difficult-to-treat infections”, says\u00a0Torrents<\/strong>.<\/p>\n

The next step is to work towards the clinical validation of this system. Its commercialization would represent a critical step forward in the treatment of biofilm infections \u2013 for which the global economic toll currently stands at US$4,000 billion per year.<\/p>\n

\n

\u00bb Reference article: <\/strong>N\u00faria Blanco-Cabra, Julie Movellan, Marco Marradi, Raquel Gracia, Cristian Salvador, Damien Dupin, Iraida Loinaz & Eduard Torrents.\u00a0Neutralization of ionic interactions by dextran-based single-chain nanoparticles improves tobramycin diffusion into a mature biofilm. npj Biofilms Microbiomes 8, 52 (2022). DOI:\u00a0https:\/\/doi.org\/10.1038\/s41522-022-00317-9<\/a><\/p>\n

\u00bb Link to the news: IBEC websites [+]<\/a><\/strong><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

A new triple-acting antibiotic agent has managed to break through the biofilm extracellular matrix \u2013 a protective structure built by bacteria \u2013 and eliminate more than 50% of the pathogens…<\/p>\n","protected":false},"author":14,"featured_media":77473,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[36],"tags":[],"class_list":["post-77476","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science"],"acf":[],"yoast_head":"\nBreaking down bacteria\u2019s protective structure to overcome antibiotic resistance - Parc Cient\u00edfic de Barcelona<\/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:\/\/www.pcb.ub.edu\/en\/breaking-down-bacterias-protective-armor-to-overcome-antibiotic-resistance\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Breaking down bacteria\u2019s protective structure to overcome antibiotic resistance - 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