SAN DIEGO, CA (PRWEB) NOVEMBER 11, 2016

In addition to living in a free-floating “planktonic” state within aqueous environments, bacteria can also colonize solid surfaces present at liquid-solid and air-solid interfaces. Within these microenvironments the bacteria “speak” to each other via chemical messengers to coordinate gene expression profiles in ways that promote survival of the colony. A common feature of these bacterial communities is the secretion of polymeric substances (polysaccharides, nucleic acids, proteins, etc.) which serve to encapsulate the cells and protect them from the environment. These “biofilms” enhance antibiotic resistance as much as 10,000-fold and play critical roles in human health and disease, including: dental plaques and cavities, infections, rejection of artificial implants, and food poisoning. Though developing drugs to treat biofilms – or prevent their formation in the first place – is of critical importance, existing assays for assessing biofilm formation and growth are time consuming and low throughput. Microtiter plate endpoint assays wherein adherent bacteria are stained with crystal violet are currently the most common type of assay used.

Last month Patricia Ruas-Madiedo and colleagues demonstrated in the journal PLOS ONE use of the xCELLigence Real-Time Cell Analysis (RTCA) technology for monitoring the biofilms produced by clinically relevant bacterial species including Staphylococcus epidermidis and Streptococcus mutans. Biofilm-producing strains could readily be differentiated from non-producing strains using this technique. Importantly, the authors showed that treating bacteria either before or after biofilm production with cell wall-degrading endolysin enzymes or with bacteriophage result in a decreased xCELLigence signal that correlates with mitigation of the bacteria. These proof of concept studies represent a major step forward as they demonstrate the ability to quantitatively track in a continuous manner the state of biofilms without having to use labels or labor intensive protocols. Adoption of this approach has the potential to dramatically accelerate screening programs focused on discovery/development of drugs for preventing biofilm formation or destroying it once it has been established.

To view full publication, click here.

Learn more about xCELLigence RTCA, and how it is being used for diverse applications.

About xCELLigence®
ACEA’s xCELLigence® Real Time Cell Analysis (RTCA) instruments utilize gold microelectrodes embedded in the bottom of microtiter wells to non-invasively monitor the status of adherent cells using the principle of cellular impedance. In short, cells act as insulators – impeding the flow of an alternating microampere electric current between electrodes. This impedance signal is measured automatically, at an interval defined by the user (e.g. every 10 seconds, once per hour, etc.), and provides an extremely sensitive readout of cell number, cell size/shape, and cell-substrate attachment strength.

About ACEA Biosciences
Founded in 2002, ACEA Biosciences is a pioneer in the development and commercialization of high performance, cutting edge cell analysis platforms for life science research. ACEA’s xCELLigence® impedance-based, label-free, real-time cell analysis instruments and NovoCyte® flow cytometers are used in pre-clinical drug discovery and development, toxicology, safety pharmacology, and basic academic research.

For further information please contact:
ACEA Biosciences, Inc.
Dr. Jeff Xue
Phone: +1 858 724 0928 x 3075

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Fiona Macdonald 23 Jun 2016

Researchers have discovered a compound in an Antarctic sea sponge that’s capable of killing 98 percent of the drug-resistant superbug, methicillin-resistant Staphylococcus aureus – better known as MRSA – which is rapidly spreading throughout the US.

With more and more bacteria species becoming resistant to the antibiotics we have available, scientists are desperately looking for new ways to protect against infection, and early research suggests that the Antarctic sponge could be an option.

Staphylococcus aureus – or staph – infections are pretty common, particularly in hospital settings, and under normal circumstances they’re not particularly hard to treat. But MRSA is a strain that’s developed resistance to most of the antibiotics we have available, which means it can quickly spread from a superficial infection, such as a skin infection, to an invasive one, which can be life-threatening.

According to the Centres for Disease Control (CDC), around 80,000 MRSA infections are diagnosed in the US each year, and 11,000 people die from MRSA complications – and right now, we really don’t have many options to fight them.

Which is why the discovery of this new compound, which has been named ‘darwinolide’, is so exciting. Researchers found it inside an Antarctic sponge, Dendrilla membranosa, and initial lab tests have shown that it’s able to kill 98.4 percent of MRSA cells.

“It’s a defensive compound against microbes with some very interesting properties,” said one of the researchers, James McClintock, from the University of Alabama at Birmingham.

It’s still very early days, but this isn’t the first time that medically interesting compounds have been founding lurking in the ocean organisms in Antarctica – McClintock and his team have already identified a compound in algae that fights the H1N1 strain of the flu virus, and another that acts against melanoma skin cancer.

The appeal for biologists is that the region is so extreme that life has been forced to come up with some unique ways to survive – including some potent defence mechanisms, such as toxic compounds.

“Sponges aren’t protected by shells and they can’t move around,” says McClintock – who adds that this leaves them without any physical defence against the bacteria-laden water they live in. “When you’re that leaky, you have a constant battle on your hands.”

The sea sponge’s solution is to produce a whole range of “nasty compounds” that kill bacteria on contact, in the hopes of keeping itself free of infections.

And McClintocks’ team has now been able to isolate one of those – darwinolide – and have shown that it has huge potential, in the lab at least, when it comes to fighting MRSA.

The researchers have now patented the compound, but are still in the process of understanding exactly how it works. Lab tests so far suggest that it has a unique structure that allows it to penetrate the ‘biofilm’ that MRSA throws up to protect itself from treatments.

“When we take antibiotics, they’re chasing bacteria in fluids,” says McClintock – which is why they’re so often useless against MRSA.

“Darwinolide differs from previous, somewhat similar, drug candidates from sponges because its central ring structure is rearranged in an unusual way,” added one of the researchers, Charles Amsler.

“If that rearrangement of the chemical backbone is in part responsible for the effectiveness against biofilm bacteria, it might be able to serve as a chemical scaffold for the development of other kinds of drugs targeting pathogens within biofilms.”

The next step is to synthesize darwinolide in the lab, so they don’t have to rely on extracting it from live Antarctic sponges. This will provide further insight about its structure, and will help the team work out exactly how it fights MRSA, and whether it could be turned into a treatment one day.

If the researchers are able to show that they can use darwinolide to fight MRSA in a clinical setting, it could save the lives of tens of thousands of people every years, so we’re pretty keen to see what happens next.

The research has been published in Organic Letters.

Researchers at Thomas Jefferson University and the National Institutes of Health are building on their research which seeks to understand why joint infections persist despite standards of care designed to stop them. More Americans than ever will receive joint replacements, and with an infection rate of approximately 1 percent, the potential exists for tens of thousands to experience post-operative infection and complications each year.

“In this study, we decided to find out if pre-operative, prophylactic antibiotic concentrations in joint fluid samples from patients were sufficient to prevent Staphylococcus aureus and MRSA contamination,” says Noreen Hickok, PhD, associate professor in the Department of Orthopedic Surgery in the Sidney Kimmel Medical College at Thomas Jefferson University. “We found that high concentrations of the preferred antibiotic cefazolin are present in the synovial fluid. But when bacteria are introduced into this environment, the bacteria survive and continue to grow and form clumps.”

Importantly, when Staphylococcus aureus was introduced into joint fluid, the bacteria was still able to colonize model implant surfaces, i.e. titanium pins, and form biofilms. The persistence of these bacteria in synovial fluid containing antibiotics may be one reason that joint infection is so difficult to cure.

The team’s previous research identified these floating biofilm-like clumps of bacteria as a source of antibiotic-resistant joint infections. These biofilm-like clumps arise because bacteria embed themselves in a protective mesh of proteins that resist the penetration of antibiotics. They also found that the bacteria slow their growth, making them even less susceptible to antibiotics, which are designed to target rapidly growing cells like bacteria.

“The next step is to see how we can disperse these mega-clusters of buried bacteria. If we can provide a window for antibiotics to carry out their intended function, we can move towards a clinical model and ultimately cure joint infection,” says Sana Dastgheyb, PhD, lead author on this study and researcher at both Thomas Jefferson University and the National Institutes of Health.

Reference: S.S. Dastgheyb, et al. Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin. Antimicrob. Agents Chemother, doi:10.1128/AAC.04579-14, 2015.

Source: Thomas Jefferson University

See:Why Am I Still Sick?

Make sure to click on the VHX links — not the DVD purchase — unless of course you want to buy the DVDs. The actual link is here:

https://whyamistillsick.vhx.tv/buy/why-am-i-still-sick-the-silent-role-of-biofilms-in-chronic-disease-1

“The results are very promising . . . However, before real recommendations can be made, it should be verified if the antibacterial regimes actually lead to less gingivitis and caries in the clinical situation,” Jongsma said.
International Journal of Oral Science – In vivo biofilm formation on stainless steel bonded retainers during different oral health-care regimens