{"id":12661,"date":"2017-10-30T10:21:32","date_gmt":"2017-10-30T16:21:32","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=12661"},"modified":"2024-12-24T09:28:04","modified_gmt":"2024-12-24T16:28:04","slug":"in-health-care-as-in-sports-consistency-is-key-2","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/","title":{"rendered":"Tracking and fighting antibiotic resistance"},"content":{"rendered":"
<\/div>
\"This
Courtesy: Centers for Disease Control and Prevention.<\/figcaption><\/figure>\n

Science can border on science fiction. Designing swarms of infinitesimal semiconductors that, shined with green light, turn standard oxygen into a superoxide that makes life hell for drug-resistant bacteria \u2013 that qualifies.<\/p>\n

A diverse University of Colorado team led by Anushree Chatterjee, PhD, did just that. Chatterjee, an assistant professor of chemical and biological engineering at CU Boulder, teamed with colleague Prashant Nagpal, PhD, to design and create these quantum-dot semiconductors and establish that they worked. To test them, they sought some of the toughest, nastiest microorganisms they could get their hands on. They turned to Nancy Madinger, MD<\/a>, at UCHealth University of Colorado Hospital (UCH).<\/p>\n

Madinger, an infectious disease specialist and medical director of UCH\u2019s Clinical Microbiology Laboratory, opened a freezer set to minus-106-degrees Fahrenheit one recent morning. Inside frosty boxes, the Microbiology Lab stores about 15,000 samples of what she refers to simply as \u201corganisms\u201d collected over the past two decades. The collection\u2019s main purpose is day-to-day infection control and patient care \u2013 her lab continually runs tests that, among many other things, help physician colleagues identify what\u2019s causing an infection and what drug or drugs might best stop it. Then they freeze and store the samples. Because UCH treats many seriously ill, immunocompromised patients, it\u2019s a trove from the perspective of those tracking and fighting antibiotic resistance.<\/p>\n

Antibiotic resistance<\/h3>\n

\u201cAntibiotics came into general use after World War II. For about 50 years, we were winning,\u201d Madinger said. \u201cBut for the past 20 years, we\u2019ve been losing. Unfortunately, that\u2019s been accelerating, and in the past five years, it\u2019s become quite dire.\u201d<\/p>\n

Michelle Barron, MD<\/a>, medical director for infectious disease at UCH, put the antibiotic resistance problem in the really long-term context.<\/p>\n

\"Nancy
Nancy Madinger, MD, with samples stored at a cool minus-106 degrees.<\/figcaption><\/figure>\n

\u201cBacteria have been here how many millions of years compared to humans? And how did they survive all these crazy temperatures and dinosaurs and asteroids? They adapted,\u201d Barron said. \u201cDrug resistance is just another adaptation.\u201d<\/p>\n

Madinger said she used to came across infections that were \u201cvery hard to treat,\u201d but could usually find a drug in the pipeline to handle it.<\/p>\n

\u201cAnd now I can\u2019t,\u201d she said.<\/p>\n

She\u2019s not just sitting back and lamenting that fact. In addition to her work with Chatterjee, she\u2019s submitting organisms to six studies aimed at tracking antibiotic resistance on a national scale, Madinger said. In addition, the pharmaceutical companies tap into growing collection to test new drugs, she added.<\/p>\n

Fearsome five<\/h3>\n

The organisms Chatterjee wanted were the sorts of \u201csuperbugs\u201d driving today\u2019s epidemic of bacterial drug resistance, one infecting an estimated 2 million people and killing 23,000 each year in the United States, and at a cost of about $20 billion in direct health care expenses alone. The worst of these are multi-drug-resistant bacteria, which, true to their name, have evolved to shrug off assaults from one antibiotic after another.<\/p>\n

Madinger and Chatterjee settled on a microbial rogue\u2019s gallery of a few dozen strains from the deep-freeze, which Chatterjee\u2019s team DNA-sequenced and reduced to a handful, including methicillin-resistant Staphylococcus aureus<\/em> (MRSA); Klebisella pneumoniae<\/em>; Salmonella typhimurium<\/em>; and two E. coli <\/em>strains, one of which was resistant to no fewer than nine antibiotics.<\/p>\n

Chatterjee\u2019s idea was sparked by previous science that showed bacteria under antibiotic assault to have slightly higher volumes of reactive oxygen species, which are molecules that oxidize other molecules by robbing them of electrons. The same thing happens when oxygen in the air causes metal to rust.<\/p>\n

\u201cSo we thought, \u2018How about we engineer antibiotics that create a controlled amount of reactive oxygen species?\u2019\u201d Chatterjee said.<\/p>\n

Go small<\/h3>\n

To do that, she enlisted Nagpal, a nanomaterials expert, who came up with cadmium-telluride semiconductors just two to four nanometers (billionths of a meter) across \u2013 small enough to penetrate bacterial cell walls. They would stay inert unless exposed to a particular green light (one with a wavelength of about 520 nanometers). The light would awaken nanoparticles as if someone had opened the blinds on a bright morning, causing them to kick off electrons in a sort of protest. Those electrons would be of an energy precisely calculated to transform the oxygen floating in and around the nanoparticle-infused bacteria into a superoxide bath, which Chatterjee and Nagpal figured would kill bacteria.<\/p>\n

In a Nature Materials<\/em> report<\/a> published in January 2016, they showed that it worked. In a follow-up Science Advances<\/em> paper<\/a> published this month, they combined the nanoparticles with antibiotics the bacteria were otherwise resistant to. They found that the nanoparticles paved the way for the antibiotics to work far better than they otherwise would have.<\/p>\n

The nanoparticles work as an antibiotic supercharger, Chatterjee said, because the bacteria must divert resources to overcome the superoxide stress broadly imposed on their biological workings. That makes them more susceptible to antibiotics. Traditional antibiotics, in contrast, rely on small molecules that, for example, might try to blow holes in a bacteria\u2019s cell wall.<\/p>\n

\u201cConventional small molecules target proteins,\u201d Chatterjee said. \u201cAnd here we target a process.\u201d<\/p>\n

Need to evolve<\/h3>\n

Because that process involves many of the systems that make bacteria tick, that process should be harder for them to overcome than the targeted assaults of small molecules, Madinger said.<\/p>\n

\u201cWe will always be working with a moving target because bacteria are very clever,\u201d she said. \u201cIf we develop something that targets something on their cell wall, they\u2019ll figure out a way to modify their cell wall and survive.\u201d<\/p>\n

These semiconducting-nanoparticle-induced superoxides, though, exploit the fact that bacteria are killed by reactive oxygen species \u2013 \u201cit\u2019s taking advantage of a lethal foe that they already have,\u201d as Madinger put it.<\/p>\n

Given the need for exposing the nanoparticles to light, the approach shows the most promise for infections at or near the surface of the skin \u2013 in particular, those associated with wounds or burns. There\u2019s certainly many who could benefit, said Laura Madsen, RN, burn outreach coordinator for the Burn Center at UCH<\/a>.<\/p>\n

\u201cInfection is still the major thing that kills burn patients,\u201d she said.<\/p>\n

Chatterjee said the next step is to move forward with larger animal models (so far, they\u2019ve gone as far as flatworms), and she hopes to further partner with physician faculty to speed up the process of moving her work from the brink of science fiction to patients and UCHealth and beyond.<\/p>\n

\u201cWe should be evolving in a way that can keep up with evolving pathogens,\u201d she said.<\/p>\n

Which is to say: very, very quickly.<\/p>\n","protected":false},"excerpt":{"rendered":"

Science can border on science fiction. Designing swarms of infinitesimal semiconductors that, shined with green light, turn standard oxygen into a superoxide that makes life hell for drug-resistant bacteria \u2013 that qualifies. A diverse University of Colorado team led by Anushree Chatterjee, PhD, did just that. Chatterjee, an assistant professor of chemical and biological engineering […]<\/p>\n","protected":false},"author":23,"featured_media":12670,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[5],"tags":[586,4293],"class_list":["post-12661","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-innovative-care","tag-laboratory","tag-uchealth-burn-and-frostbite-center"],"acf":[],"yoast_head":"\nTracking and fighting antibiotic resistance - UCHealth Today<\/title>\n<meta name=\"description\" content=\"Science can border on science fiction. 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Chatterjee, an assistant professor of chemical and biological engineering […]","og_url":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/","og_site_name":"UCHealth Today","article_publisher":"https:\/\/www.facebook.com\/uchealthorg\/","article_published_time":"2017-10-30T16:21:32+00:00","article_modified_time":"2024-12-24T16:28:04+00:00","og_image":[{"url":"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2017\/10\/30050935\/editedfeaturephoto.jpg","type":"image\/jpeg"}],"author":"Todd Neff, for UCHealth","twitter_card":"summary_large_image","twitter_creator":"@uchealth","twitter_site":"@uchealth","twitter_misc":{"Written by":"Todd Neff, for UCHealth","Est. reading time":"6 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/#article","isPartOf":{"@id":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/"},"author":{"name":"Todd Neff, for UCHealth","@id":"https:\/\/www.uchealth.org\/today\/#\/schema\/person\/da7733ff5562e48e55c027d111ee5911"},"headline":"Tracking and fighting antibiotic resistance","datePublished":"2017-10-30T16:21:32+00:00","dateModified":"2024-12-24T16:28:04+00:00","mainEntityOfPage":{"@id":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/"},"wordCount":1107,"publisher":{"@id":"https:\/\/www.uchealth.org\/today\/#organization"},"image":{"@id":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/#primaryimage"},"thumbnailUrl":"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2017\/10\/30050935\/editedfeaturephoto.webp","keywords":["Laboratory","UCHealth Burn and Frostbite Center"],"articleSection":["Innovative care"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/","url":"https:\/\/www.uchealth.org\/today\/in-health-care-as-in-sports-consistency-is-key-2\/","name":"Tracking and fighting antibiotic resistance - 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