Nanotechnology Now

Our NanoNews Digest Sponsors
Heifer International

Wikipedia Affiliate Button

Home > Press > Tracking a Killer: UCSB, UCSD and SBP researchers trace the complex and variable pathways to the deadly condition known as sepsis

Abstract:
A major cause of human disability and death throughout the world, sepsis is a condition that begins with an infection, progresses rapidly and can set off a chain of effects that result in multiple organ failure and irreparable damage to the body. Because of the condition’s rapid onset, physicians must respond immediately to the symptoms with broad-spectrum antibiotics for infection, drugs to combat inflammation and, in the more critical cases, vasopressors to manage shock.

Tracking a Killer: UCSB, UCSD and SBP researchers trace the complex and variable pathways to the deadly condition known as sepsis

Santa Barbara, CA | Posted on October 12th, 2018

Because sepsis is so difficult to detect in its early stages, however, little has been known about how it develops. This may explain why no new effective drugs to treat sepsis have been developed in decades, while it remains one of the leading causes of hospital deaths. Sepsis also can result in serious disabilities for those who survive.

Now, researchers at UC Santa Barbara, Sanford Prebys Medical Discovery Institute (SBP) in La Jolla, California, and UC San Diego have developed a method for tracking, on a molecular level, the development of sepsis. Their resulting discoveries could, in turn, lead to more advanced therapies for sepsis that reduce its mortality, minimize the lifelong effects for survivors or even prevent the cascade of life-threatening effects before it begins, while reducing the billions of dollars spent every year to treat the condition.

Their paper, “Accelerated Aging and Clearance of Host Anti-inflammatory Enzymes by Discrete Pathogens Fuels Sepsis” is published in the journal Cell Host & Microbe.

“Sepsis is generally thought of as one singular disease, especially as it enters late stages,” said UC Santa Barbara biology professor Jamey Marth, who is the director of the campus’s Center for Nanomedicine, in addition to being a professor at SBP. “At this point, inflammation and coagulopathy have caused the vascular and organ damage common to severe sepsis and septic shock. Our comparative approach to monitor the onset and progression of sepsis at the molecular level supports the view that there are different molecular pathways in sepsis depending on host responses to different pathogens.”

An improved sepsis model yields important findings
In contrast to previous experimental models of sepsis, which typically release multiple and incompletely identified pathogens into the bloodstream, Marth and his team developed a more quantitative method that tracked the pathogen and host over time, beginning with infection. This method generated a reproducible protocol that allowed the scientists to map host responses, in this case to five different human pathogens representing common strains and isolates from different patients.

In the study, Marth’s team found that in the onset and progression of sepsis caused by Salmonella or E. coli, a protective mechanism normally present in the host was disabled. The mechanism that the bacteria used included a means to accelerate the molecular aging and clearance of two anti-inflammatory alkaline phosphatase (AP) enzymes, called TNAP and IAP, which are normally present in the host bloodstream. This was achieved through pathogen activation of the host’s own Toll-like receptor-4 (TLR-4), and both pathogens were thus able to induce inflammatory compounds and reduce the likelihood of host survival.

The scientists found that boosting the level of protective anti-inflammatory AP activity or using neuraminidase inhibitors to block the downstream effect of TLR-4 activation on NEU1 and NEU3 induction were both highly therapeutic approaches as inflammatory markers were reduced and host survival increased — indicating a potential direction for drug development.

“It has been known that AP isozymes can reduce inflammation in the context of some diseases and pathogens — indeed AP is currently in clinical trials focused on inflammatory diseases, including colitis and sepsis,” said Won Ho Yang, Ph.D., lead author and a senior scientist in the Marth laboratory at both UCSB and SBP. “This study shows that the pathogen is interacting with the host to disable a protective response. The findings also demonstrate how both pathogen and host battle each other by altering the rates of protein aging and clearance — which itself is a newly discovered regulatory mechanism we recently reported that controls the half-lives of proteins in the blood.”

In contrast, these responses weren’t seen in infections caused by other bacteria tested, including methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. The different host responses in this case appeared divided between Gram-positive and Gram-negative bacteria, which describes the existence or absence of an inflammatory compound found on Gram-negative strains.

“We are continuing to map and compare host responses to different pathogens in sepsis, using state-of-the-art technical approaches, and hope to ultimately stratify the disease,” said Marth, who is the Carbon Professor of Biochemistry and Molecular Biology at UC Santa Barbara, as well as the Mellichamp Chair of Systems Biology. “It’s possible that sepsis is similar to cancer, in that we now know that cancer is a not a single disease but represents hundreds of diseases at the molecular level.”

Research on this project was also conducted by Douglas M. Heithoff, Peter V. Aziz, Benjamin Haslund-Gourley and Michael J. Mahan, SBP and UC Santa Barbara; Julia S. Westman, Sonoko Narisawa, Anthony B. Pinkerton and José Luis Millán, SBP; and Victor Nizet, M.D., UC San Diego.

Research reported in this press release was supported by National Institutes of Health (NIH) Heart, Lung, and Blood Institute (HLBI) grants HL125352 and HL131474. Additional support was provided by the Swedish Research Council 2017-00192 and the Wille Family Foundation.

####

For more information, please click here

Contacts:
Sonia Fernandez
(805) 893-4765
sonia(dot)fernandez(at)ucsb(dot)edu

Copyright © University of California, Santa Barbara

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Govt.-Legislation/Regulation/Funding/Policy

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Researchers reverse the flow of time on IBM's quantum computer March 14th, 2019

When semiconductors stick together, materials go quantum: A new study led by Berkeley Lab reveals how aligned layers of atomically thin semiconductors can yield an exotic new quantum material March 12th, 2019

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

Possible Futures

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Nanomedicine

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

New optical imaging system could be deployed to find tiny tumors: Near-infrared technology pinpoints fluorescent probes deep within living tissue; may be used to detect cancer earlier March 8th, 2019

Computer-designed vaccine elicits potent antibodies against RSV: The nanoparticle platform for this respiratory syncytial virus study will be applied to vaccine research on flu, HIV, and more; Seattle startup Icosavax will advance related clinical trials March 8th, 2019

CEA-Leti Breakthrough Opens Path to New Vaccine for HIV: Lipidots Platform Strengthens Immune Response to Protein That Is Key to HIV Vaccine; Results Presented in Nature Publishing Group’s npj Vaccines February 27th, 2019

Discoveries

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Quantum sensing method measures minuscule magnetic fields: MIT researchers find a new way to make nanoscale measurements of fields in more than one dimension March 15th, 2019

Announcements

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Quantum sensing method measures minuscule magnetic fields: MIT researchers find a new way to make nanoscale measurements of fields in more than one dimension March 15th, 2019

Grants/Sponsored Research/Awards/Scholarships/Gifts/Contests/Honors/Records

Quantum sensing method measures minuscule magnetic fields: MIT researchers find a new way to make nanoscale measurements of fields in more than one dimension March 15th, 2019

Researchers reverse the flow of time on IBM's quantum computer March 14th, 2019

Pushing Past Limits: Junkai Jiang receives prestigious Ph.D. Student Fellowship from IEEE Electron Devices Society March 14th, 2019

When semiconductors stick together, materials go quantum: A new study led by Berkeley Lab reveals how aligned layers of atomically thin semiconductors can yield an exotic new quantum material March 12th, 2019

Nanobiotechnology

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

Computer-designed vaccine elicits potent antibodies against RSV: The nanoparticle platform for this respiratory syncytial virus study will be applied to vaccine research on flu, HIV, and more; Seattle startup Icosavax will advance related clinical trials March 8th, 2019

Nanotechnology Gives Mice Night Vision—Are Humans Next? March 2nd, 2019

CEA-Leti Breakthrough Opens Path to New Vaccine for HIV: Lipidots Platform Strengthens Immune Response to Protein That Is Key to HIV Vaccine; Results Presented in Nature Publishing Group’s npj Vaccines February 27th, 2019

Research partnerships

Lightweight metal foams become bone hard and explosion proof after being nanocoated March 14th, 2019

When semiconductors stick together, materials go quantum: A new study led by Berkeley Lab reveals how aligned layers of atomically thin semiconductors can yield an exotic new quantum material March 12th, 2019

AIM Photonics Attends OFC 2019—the Optical Networking and Communication Conference & Exhibition to Share World-Class Capabilities and Partnership Opportunity Updates February 28th, 2019

CEA-Leti Breakthrough Opens Path to New Vaccine for HIV: Lipidots Platform Strengthens Immune Response to Protein That Is Key to HIV Vaccine; Results Presented in Nature Publishing Group’s npj Vaccines February 27th, 2019

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project