Connect with us

BIOLOGY

Lysin therapy offers new hope for fighting drug-resistant bacteria

HPSN

Published

on

Humans are in a constant arms race with infectious bacteria. To kill these disease microbes, we develop powerful antibiotics; and in turn, the bacteria develop resistance against these drugs. So we enhance our antibiotics, and the bacteria enhance themselves accordingly—resulting in so-called superbugs. Increasingly, medications fail to eliminate these highly adapted bacteria, leaving our bodies dangerously defenseless.

In light of this crisis, for almost 20 years Rockefeller’s Vincent A. Fischetti has been developing a novel form of antimicrobial ammunition known as lysins. Now, these bacteria-killing enzymes have been studied in a phase II human clinical trial, becoming the first antibiotic alternatives to achieve successful outcomes in this stage of clinical development.

Natural born killer

Some viruses are very good at killing bacteria. Known as bacteriophages, or simply phages, these viruses infect a microbe, replicate inside of it, and then produce lysin enzymes, which cleave the bacterium’s cell wall. As a result, progeny phages are released from within the bacterium, and the bacterium itself perishes.

In nature, this kind of assault is commonplace: bacteriophages inhabit everything from oceans and soil to human bodies, helpfully regulating microbe populations wherever they go. In fact, every 48 hours half the bacteria on earth are killed by phages, making lysins the most widespread bacteria-killing agents on Earth.

In the lab, lysins can be used as a tool to break down and study the cell walls of bacteria—which is exactly what Fischetti was doing at Rockefeller about two decades ago. Simultaneously, his lab was also working on a vaccine for streptococcus infections, and the broader research community was becoming increasingly worried about antibiotic-resistant infections. This confluence of events led Fischetti to a breakthrough.

“Since I was working with lysins, I knew they killed bacteria instantly. My lab happened to have animals that were orally colonized with streptococci for my vaccine studies,” he recalls. “So, I thought, let me just give these colonized mice some lysin and see what happens to the streptococci.”

The effect was dramatic: an hour after getting the drug, the animals were decolonized of their streptococci. The subsequent publication of this finding was the first to report the therapeutic use of phage lysins.

Compelled by this result, Fischetti and later other scientists began developing lysins against several types of drug-resistant bacteria, many of which successfully cured infections in a wide range of animal models. Until recently, however, no one had tested whether this type of therapy was safe and effective in humans.

A new approach

Drug-resistant bacteria are especially dangerous—and especially common—in hospitals, where infection can complicate the outcomes of already-sick patients. Of particular concern in this setting is infection with methicillin-resistant Staphylococcus aureus (S. aureus), or MRSA. Though some cases of MRSA are mild, the bacterium can be life-threatening if it spreads to the blood, a condition known as bacteremia.

As the “methicillin-resistant” part of its name suggests, MRSA doesn’t respond to standard antibiotics—which makes it an ideal candidate for treatment with a new kind of bacteria killer. To this end, seven and a half years ago the biotechnology company ContraFect licensed from Rockefeller a lysin that targets Staphylococci, as well as some Streptococci. The company then developed the lysin, now called exebacase, for the treatment of human S. aureus infections, including MRSA.

Following a phase I clinical trial showing that exebacase did not lead to any serious side effects in humans, ContraFect advanced the research into a randomized, double-blind, placebo-controlled phase II study of hospitalized patients with S. aureus bacteremia, approximately one third of whom had MRSA. 116 of these patients were randomly assigned to receive either exebacase or placebo, in addition to antibiotic therapy, and were followed for fourteen days. The researchers found that the rate of treatment response was more than 40 percent higher for MRSA patients receiving exebacase than for those treated with antibiotics alone—a result Fischetti views as very encouraging not only for exebacase, but for lysins at large.

“This is the first time a lysin-based drug has gone this far in clinical development. In fact, there is no antibiotic alternative that has ever successfully completed phase II trials,” he says. “More work needs to be done, but this study is very promising.”

Moving forward, ContraFect intends to conduct a larger phase III trial, which is necessary for the lysin to be approved as a medicine.

Fischetti hopes that the development of exebacase is part of broader shift in how researchers and clinicians think about the management of bacterial infections. “Bacteria are growing more and more resistant to antibiotics,” he says. “And we’re showing that there are other ways to fight them.”


Explore further:
Newly engineered enzyme is a powerful staph antibiotic

Provided by:
Rockefeller University

Continue Reading
Advertisement
Click to comment

Leave a Reply

Your email address will not be published. Required fields are marked *

Medical News

MEDICAL10 hours ago

Quick Take: Association of Systemic Antibiotic Treatment of Acne With Skin Microbiota Characteristics

Systemic antibiotics are commonly used in the treatment of acne. However, the impact of their use on the complete bacterial...

MEDICAL10 hours ago

New herpes zoster vaccine predicted to be more cost effective than predecessor  

1. In a computational model, the new “recombinant zoster vaccine” (RZV) was predicted to be most cost-effective than the previous...

MEDICAL22 hours ago

Chinese population study shows high prevalence of elevated cardiovascular disease risk and low utilization of pharmacotherapy

1. In this national screening project, around 10% of middle-aged Chinese subjects were found to be at “high risk” for...

MEDICAL1 day ago

The KATHERINE trial: trastuzumab emtansine more effective than trastuzumab alone for treating residual HER2-positive breast cancer

1. Patients with residual human epidermal growth factor receptor 2 (HER2)-positive breast cancer after chemotherapy and HER2 targeted therapy had...

MEDICAL2 days ago

Peripheral perfusion-targeted resuscitation does not lower mortality in septic shock patients

1. In this randomized controlled trial, there was no difference in 28-day mortality in patients with early septic shock between...

MEDICAL2 days ago

The CLEAR trial: decolonization routine associated with lower infection risk among MRSA carrier patients

1. Hospitalized patients with known MRSA colonization randomized to undergo a decolonization routine were found to have lower risks of...

MEDICAL3 days ago

Addition of IV acetaminophen with propofol or dexmedetomidine reduces risk of post-operative delirium in older patients undergoing cardiac surgery

1. In this randomized controlled trial, post-operative scheduled intravenous (IV) acetaminophen combined with propofol or dexmedetomidine reduced risk of post-operative...

MEDICAL3 days ago

Nurse-led psychological intervention does not reduce PTSD symptoms in ICU patients

1. In this randomized clinical trial, nurse-led psychological interventions did not reduce PTSD risk at 6 months compared to care...

MEDICAL4 days ago

2-Question Screen Identifies Adolescents at Risk for Future Alcohol Use Disorders

1. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) 2-question screen showed high predictive validity in identifying adolescents at...

MEDICAL4 days ago

MYBPC3 haploinsufficiency results in hypertrophic cardiomyopathy by altering myosin head configurations [PreClinical]

1. Truncating mutations in cardiac myosin-binding protein C (MYBPC3) are a common genetic cause of hypertrophic cardiomyopathy. 2. Haploinsufficiency of...

Advertisement

#CDC

Do you have questions about preventing and managing high #cholesterol? Join @CDCHeart_Stroke and a panel of cholesterol experts for a Facebook Live event on February 25 at 12:30 pm ET. Tune in at facebook.com/millionhearts. #HeartMonth

test Twitter Media - Do you have questions about preventing and managing high #cholesterol? Join @CDCHeart_Stroke and a panel of cholesterol experts for a Facebook Live event on February 25 at 12:30 pm ET. Tune in at https://t.co/rLdeAt7cyx. #HeartMonth https://t.co/6FGXEgv6Wu

HCPs: People with #disabilities are 3 times more likely to have #heartdisease than those without disabilities. In honor of #AmericanHeartMonth, help your patients explore the physical activities suitable for their disability type. bit.ly/2EnsTBx

test Twitter Media - HCPs: People with #disabilities are 3 times more likely to have #heartdisease than those without disabilities. In honor of #AmericanHeartMonth, help your patients explore the physical activities suitable for their disability type. https://t.co/9O33ubwifA https://t.co/SpXpDqLgcP

@Raelove03 CWD and Bovine Spongiform Encephalopathy (BSE, or “Mad Cow Disease”) are both animal prion diseases, a family of rare progressive neurodegenerative disorders. CWD affects deer, elk, reindeer, sika deer and moose, while BSE affects cows.

@Mad_Scientist25 Yes - Chronic Wasting Disease (CWD) is a prion disease that affects deer, elk, reindeer, sika deer and moose. To date, there have been no reported cases of CWD infection in people.

Hunters - be as safe as possible and lower your potential risk of exposure to #ChronicWastingDisease. Take CDC’s recommended steps when hunting in areas with #CWD: bit.ly/2EnQPox.

test Twitter Media - Hunters - be as safe as possible and lower your potential risk of exposure to #ChronicWastingDisease. Take CDC’s recommended steps when hunting in areas with #CWD: https://t.co/aPy5xs4T13. https://t.co/fjxEezzJJt

#lymedisease

@CDC_AMD Hey, can we get more $$$ for research and treatment for #Lymedisease ? Monitoring has done absolutely nothing in regards to testing, treatment, research. It's INSANE that nothing has been done for 40 years about tick borne illnesses.

A negative test does not rule out #LymeDisease Learn more about how to diagnose Lyme here: buff.ly/2sNSHjc

test Twitter Media - A negative test does not rule out #LymeDisease Learn more about how to diagnose Lyme here: https://t.co/OssrqDlLkD https://t.co/4uONqAtSgT

Lyme disease patients (67%) have postponed or avoided medical treatment due to discrimination, disrespect or difficulty obtaining care. #MyLymeData #LymeDisease tinyurl.com/y4rkruvm

test Twitter Media - Lyme disease patients (67%) have postponed or avoided medical treatment due to discrimination, disrespect or difficulty obtaining care. #MyLymeData #LymeDisease https://t.co/Ytok5v5oZl https://t.co/Sfs03xw5Ps

“It gave me a purpose,” she adds of her journey, “and made me find myself all over again.” @AvrilLavigne #LymeDisease #HeadAboveWater people.com/music/avril-la…

#Antiparasitic

Trending

Copyright © 2019. All Rights Reserved. The Human Parasite Support Network.