Tag: biofilm

Categories : AntibioticsTags :

Breaching Stubborn Bacterial Biofilms with a ‘Trojan Horse’

On By ModernMedia
Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

A new study has tricked bacteria into sending death signals to stop the growth of biofilms that lead to deadly infections. The discovery by Washington State University researchers could someday be harnessed as an alternative to antibiotics for treating difficult infections.

Reporting in the journal, Biofilm, the researchers used the messengers, which they named death extracellular vesicles (D-EVs), to reduce growth of the bacterial communities by up to 99.99% in laboratory experiments.

“Adding the death extracellular vesicles to the bacterial environment, we are kind of cheating the bacteria cells,” said Mawra Gamal Saad, first author on the paper and a graduate student in WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering.

“The cells don’t know which type of EVs they are, but they take them up because they are used to taking them from their environment, and with that, the physiological signals inside the cells change from growth to death.”

Bacterial resistance is a growing problem around the world. In the US, at least 2 million infections and 23 000 deaths are attributable to antibiotic-resistant bacteria each year, according to the U.S. Centers for Disease Control.

When antibiotics are used to treat a bacterial infection, some of the bacteria can hide within their tough-to-penetrate biofilm. These subpopulations of resistor cells can survive treatment and are able to grow and multiply, resulting in chronic infections.

“They are resistant because they have a very advanced and well-organised adaptive system,” said Saad.

“Once there is a change in the environment, they can adapt their intracellular pathways very quickly and change it to resist the antibiotics.”

In their new study, the researchers discovered that the extracellular vesicles are key to managing the growth of the protective biofilm.

The vesicles, tiny bubbles from 30 to 50nm or about 2000 times smaller than a strand of hair, shuttle molecules from cells, entering and then re-programming neighbouring cells and acting as a cell-to-cell communications system.

As part of this study, the researchers extracted the vesicles from one type of bacteria that causes pneumonia and other serious infections.

They determined that the bacteria initially secrete vesicles, called growth EVs, with instructions to grow its biofilm, and then later, depending on available nutrients, oxygen availability and other factors, send EVs with new instructions to stop growing the biofilm.

The researchers were able to harness the vesicles with the instructions to stop growth and use them to fool the bacteria to kill off the biofilm at all stages of its growth.

Even when the biofilms were healthy and rapidly growing, they followed the new instructions from the death EVs and died. The death EVs can easily penetrate the biofilm because they are natural products secreted by the bacteria, and they have the same cell wall structure, so the cells don’t recognise them as a foreign enemy.

“By cheating the bacteria with these death EVs, we can control their behaviour without giving them the chance to develop resistance,” said Saad.

“The behavior of the biofilm just changed from growth to death.”

WSU Professor and corresponding author Wen-Ji Dong, who has been studying the vesicles for several years initially thought that all of the bacterial-secreted vesicles would promote cell growth.

The researchers were surprised when they found that older biofilms provided instructions on shutting themselves down.

“So now we’re paying attention to the extracellular vesicles secreted by older biofilms because they have therapeutic potential,” he said.

Source: Washington State University

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Peptides May Solve the Sticky Problem of Bacterial Biofilms

On By ModernMedia
This image shows an intricate colony of Pseudomonas aeruginosa. The bacteria have self-organised into a sticky, mat-like colony called a biofilm, which allows them to cooperate with each other, adapt to changes in their environment, and ensure their survival.
Credit: Scott Chimileski and Roberto Kolter, Harvard Medical School, Boston

Researchers have developed peptides that can help combat bacteria growing in biofilms, which occur in up to 80% of human infections. Their results, published in Nature Chemical Biology, may offer a way to tackle antimicrobial-resistant infections. 

Treating infections becomes significantly more challenging when biofilms are present, as they not only reduce the effectiveness of antibiotics but also give rise to several medical complications. These complications include infections following joint replacements, prosthetic devices, as well as contamination in catheters and other medical equipment. The lack of specific treatments makes the management and treatment of biofilms exceptionally difficult.

The team of researchers, led by Dr Clarissa Melo Czekster and Dr Christopher Harding from the School of Biology at St Andrews, in collaboration with researchers at University of Dundee, developed antimicrobial peptides that can target the harmful bacteria growing in biofilms.

The team determined how a key enzyme (PaAP) in biofilms work and developed a revolutionary new strategy to inhibit the protein. Their inhibitor is potent and targets cells from the human pathogen Pseudomonas aeruginosa in biofilms. P. aeruginosa, a WHO pathogen of concern, causes chronic infections in patients with cystic fibrosis and other conditions, which means a biofilm inhibitor is urgently needed.

Dr Czekster and the team are currently working in collaboration with the University of St Andrews Technology Transfer Centre and industry partner Locate Bio, a biomedicine spinout of the University of Nottingham, to commercialise the technology. The Locate Bio team are trialling the peptides to see how they work with the company’s Programmed Drug Release technology to develop new orthobiologic solutions and products. The Technology Transfer Centre has filed a UK priority patent application.

Dr Czekster said: “Our research reveals how designed inhibitors can target a key enzyme in bacterial virulence, offering molecular insights applicable to aminopeptidases in diverse organisms.

“This remarkable new research presents an innovative strategy to target bacterial biofilms and pave the way for better treatment of bacterial infection.”

Source: University of St. Andrews

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

Ripping Through Biofilms in Chronic Treatment-resistant Wounds

On By ModernMedia
Methicillin-resistant-Staphylococcus-aureus-MRSA

Researchers have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with Staphylococcus aureus and protected by thick biofilms. Their results were published in Cell Chemical Biology.

Chronic wounds are notoriously challenging to treat because of bacterial infections like S. aureus, which can also be resistant to antibiotics.

To defend itself from the immune system and other threats, S. aureus can band together, creating a slick, slimy biofilm around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralise the harmful bacteria.

Using a new strategy, researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilise the wounds in several of the mice, and the rest had significantly reduced bacterial burden.

“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”

Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.

Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.

The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.

“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumours or drive new genetic material into damaged cells as well.”

When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.

Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persistent cells and reverse antibiotic resistance.

Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.

“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”

Source: University of North Carolina Health Care