Disrupting Bacterial Communication to Stop Infections

MiDOG technology can help detect microorganisms that are prone to communication amongst each other.

In so many aspects of life, communication is key. We, humans, communicate with each other primarily through language. Bacteria are ubiquitous around us and communicate with each other as well but through a special process called ‘quorum sensing’ [1]. ‘Quorum sensing’ is a truly fascinating process in the bacterial kingdom that scientists and physicians are just beginning to understand. Very recently, two American scientists, Drs. Michael Silverman and Bonnie Bassler, won the 2021 Paul Ehrlich and Ludwig Darmstaedter Prize for elucidating this captivating process that has a huge impact on animal and human health. Bonnie Bassler is Professor at Princeton University and a Howard Hughes Medical Institute Investigator, NJ, while Michael Silverman is Emeritus Professor of the Agouron Institute in La Jolla, CA. Paul Ehrlich was a Noble Prize-winning German Jewish physician and scientist who made significant contributions in the fields of hematology, immunology, and antimicrobial chemotherapy. The Paul Ehrlich and Ludwig Darmstaedter Prize honors scientists who have made significant contributions in Paul Ehrlich’s field of research. The Prize has been awarded annually since 1952.

What Is Quorum Sensing?

Quorum sensing describes the ability to detect bacterial cell population density and respond accordingly using gene regulation [1]. In particular, bacteria use signal molecules to gather intelligence about the neighborhood they are in, such as how many other bacteria and what species of bacteria there are present around them. They use this information to decide if or how to engage in collective activities [1].

Dr. Michael Silverman was the first scientist to discover a quorum-sensing circuit in a bioluminescent bacterium called Vibriofischeri in the 1980s [2]. He was able to pinpoint the genes and proteins involved in the production and detection of extracellular signal molecules, which in turn promote the collective behavior of blue-green bioluminescence production [2]. Such behavior is not unique to V. fischeri; in fact, thousands of bacterial species possess similar mechanisms implemented by almost identical genes to those in V. fischeri, allowing them to engage in group behaviors[1].

Highlights:

1. Bacteria can communicate with each other and with viruses and human cells using quorum sensing

2. Quorum sensing can contribute to antibiotic resistance and virulence

3. Pets are impacted by pathogens capable of quorum sensing

4. Novel anti-microbial strategies can be devised by targeting the process of quorum sensing

Bacteria Can Speak Multiple “Languages”

Subsequently in the 1990s, Dr. Bonnie Bassler discovered that bacteria communicated with each other using multiple chemical signal molecules, effectively making them “multi-lingual” [1]. One such example is the autoinducer-2 molecule that enables cross-species communication, which bacteria use to differentiate themselves from other species [1]. Such sophisticated communication mechanisms, previously thought to be exclusive to higher organisms, have in fact been in existence in the bacterial kingdom for billions of years [1]. Later on, Bassler further demonstrated that quorum sensing exists even beyond kingdom boundaries as viruses and host cells, for example, human cells, also engage in such communication [3, 4].

In addition, Bassler, among several researchers, also discovered that quorum sensing plays a key role in pathogen virulence; they demonstrated in animal models that an anti-quorum sensing strategy can effectively halt infection of bacterial pathogens [5]. Moreover, quorum sensing also aids in the process of antibiotic resistance by regulating efflux pumps, which extrude drug molecules out of bacterial cells, or by coordinating the formation of bacterial biofilms, structures of bacterial cells attaching to each other, and a self-produced matrix which cause reduced permeability of drug molecules [6].

Disrupting Bacterial Communication to Stop Infections

MiDOG diagnostic tests can help detect the presence of bacteria that participate in quorum sensing.

The discoveries of Drs. Michael Silverman and Bonnie Bassler are of significant importance in the medical field, including veterinary medicine. As aforementioned, quorum sensing plays a pivotal role in the virulence of disease-causing bacteria and in antibiotic resistance. In pathogenic bacteria such as Staphylococcusaureus and Pseudomonasaeruginosa, which are frequently diagnosed in dogs and other animals by the MiDOG Test, quorum sensing controls many traits including the expression of virulence factors, molecules produced by bacteria in order to aid its colonization of the host, evasion, and suppression of host immune system, entry and exit of host cells, and acquisition of nutrients from host cells [5].

This allows for novel anti-microbial treatment strategies to be developed by focusing on disrupting cell-to-cell communication and in turn halting infection rather than eradicating the bacteria using conventional antibiotics [5]. Such novel treatment options are urgently needed since multi-drug antimicrobial resistance is on the rise in both human and veterinary medicine. You can now aid in this effort and better diagnose bacterial infection in your pet by using our MiDOG Test to find out if your pet’s illness is caused by a bacterial species capable of quorum sensing.

References

1. Miller, Melissa B., and Bonnie L. Bassler. “Quorum sensing in bacteria.” Annual Reviews in Microbiology 55, no. 1 (2001): 165-199.

2. Dunlap, Paul V. “Quorum regulation of luminescence in Vibrio fischeri.” Journal of molecular microbiology and biotechnology 1, no. 1 (1999): 5-12.

3. Duddy, Olivia P., and Bonnie L. Bassler. “Quorum sensing across bacterial and viral domains.” Plos Pathogens 17, no. 1 (2021): e1009074.

4. Holm, Angelika, and Elena Vikström. “Quorum sensing communication between bacteria and human cells: signals, targets, and functions.” Frontiers in plant science 5 (2014): 309.

5. Rutherford, Steven T., and Bonnie L. Bassler. “Bacterial quorum sensing: its role in virulence and possibilities for its control.” Cold Spring Harbor perspectives in medicine 2, no. 11 (2012): a012427.

6. Zhao, Xihong, Zixuan Yu, and Tian Ding. “Quorum-sensing regulation of antimicrobial resistance in bacteria.” Microorganisms 8, no. 3 (2020): 425.


Categories: Antibiotic Resistance

animal diagnostics

Validated by Veterinarians

“Clients expect their veterinarians to stay up to date on all matters that affect the health and well being of their non-human family members. The current technique that we have used to determine the presence and antibiotic sensitivity of organisms causing disease in our pets is over a century old.

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Bernadine Cruz, DVM, Laguna Hills Animal Hospital Laguna Woods, CA

“I love the absolute abundance and comparing the fungal with bacterial infection. I do not worry as much about getting a false negative urinary infection reading as I do with traditional urine cultures. Several times the same urine would culture negative but MiDOG would detect pathogens.”

Michael Morgan, DVMQuail Animal Hospital, Tustin, CA

“The MiDOG All-in-One Test is amazing, I would use it instead of culture and sensitivity.  Such rapid and detailed results, I will reach for MiDOG before culture next time!

Thank you very much MiDOG, for sharing the opportunity to try your technology.”

Martha Smith-Blackmore, DVM, President of Forensic Veterinary Investigations, LLC – Boston, MA

The MiDOG All-in-One Microbial Test is our new gold standard of pathogen identification. The results are so accurate and valuable – especially with assessing both bacterial and fungal infections with the same sample.

Thank you MiDOG!”

Kathy Wentworth, DVM, Diplomate ABVP Canine and Feline Practice – PetPoint Medical Center, Irvine, CA

“The MiDOG staff was extremely helpful and supportive.”

Cathy Curtis, DVM – London, UK

“I have had great results using the MiDOG® Test. Compared to traditional culture tests, I am better able to target the treatment for dogs because the MiDOG® Test is so sensitive that it identifies all pathogens including bacteria and fungi, as well as antibiotic sensitivity.

The cost and turnaround time are about the same as a culture test, but I get much more data. The test has great performance and I believe the NGS technology will be a game changer for veterinarians treating dogs with lesions or other infections.”

Michael Kavanagh, DVM, Practice owner – Saddleback Animal Hospital, Tustin, CA

“It’s helpful to have an NGS spectrum because it gives you a broader insight of what’s happening and what might be going on.”

Richard Harvey BVSc DVD DipECVD PhD FRSB FRCVS – European Specialist in Veterinary Dermatology – Head of Dermatology, Willows Veterinary Centre & Referral Service – Solihull, England UK

“I have been using MiDog for over 4 years now and exclusively as my test of choice for all cultures for 3 years.  It is so great to submit a culture and feel confident there will be a result when it comes back, especially for urine cultures.  The reports were intimidating at first because they contain so much information.  After the first few, I am now quickly able to glance over it and pick out the highlights.  I can then come back later and pour over all the details.  I have been extremely pleased with my patients’ results using the test as well.  I don’t envision ever going back to traditional culture and susceptibilities again.”

Brian M. Urmson, DVM, Columbiana Veterinary Associates

“As an exotic veterinarian, there are numerous tests we have to consider to check specific bacterial and fungal organisms based on the species. MiDOG eliminates the need for many of these separate samples and provides definitive results quickly to help us treat our patients more efficiently and effectively. The lab is wonderful to work with and has never rejected our samples- they even processed a lizard toe we amputated and determined the cause of skin infection.”

Dr. Melissa Giese, Chicago Exotics Animal Hospital

“MiDOG’s diagnostic approach offers the unique ability to identify pathogens that evade traditional culture and sensitivity testing. I have found that adding a molecular based testing approach in the form of Next Generation Sequencing (NGS) from MiDOG to my routine diagnostic cultures can be extremely helpful in the identification and diagnosis of uncommon pathogens in veterinary medicine.”

Dr. Wayne Rosenkrantz, Animal Dermatology Clinic – Tustin

“She [Dr. Krumbeck] really did a great job of making complicated concepts accessible and demonstrating the value of your services. I’m really looking forward to working with MiDOG on my research project!”

Dr. Yaicha Peters, Animal Dermatology Clinic – San Diego

“As a proud collaborator with MiDOG, I deeply appreciate their dedication to fostering partnerships between industry and veterinary experts. Their commitment to enhancing diagnostic quality for veterinarians is commendable. In my experience, their support has been invaluable, earning them a ‘Double A+, Triple Star’ rating. Their assistance has been faultless, contributing significantly to the success of my projects and studies. I eagerly anticipate our continued collaboration.”

Dr. Richard Harvey, BVSc DVD DipECVD PhD FRSB FRCVS; European Specialist in Veterinary Dermatology

“We’re seeing that, if we prescribe too many antibiotics or they’re taken too frequently, animals are developing inappropriate or pathogenic strains of bacteria. We’re also seeing that our antibiotics are just not working against them anymore… It’s a good example of why we need better diagnostic testing, like MiDOG, so that we’re selecting the correct antibiotic every time our patients have an infection.”

Dr. Alissa Rexo, DVM, CVA, DACVD, Mid-Atlantic Veterinary Dermatology

“The NGS technique as offered by MiDOG is wonderful because pathogens like Melissococcus plutonius, for example, are difficult to grow and keep alive in the laboratory. A standard laboratory cannot truly examine or even properly diagnose this pathogen in bee hives at this time. But with NGS, we can reliably diagnose it.”

Dr. Joerg Mayer, Entomologist and Microbiologist at the University of Georgia

“For me, as a clinician and as a researcher, I see the immense value in the product [the All-in-One Test]. I have had great success using MiDOG clinically, including identifying Mycoplasma in a 24 year old pigeon, a Nannizziopsis spp in a ball python from a large pet distributor, Mycoplasma and Fusobacterium necrophorum co-infection in a peacock, and to identify an abnormal gut GI in a technician’s dog that tested negative for everything else (but we were able to establish what was abnormal, and work toward fixing it).”

Dr. Jeremy Rayl – Veterinarian, Block House Creek Animal Hospital, Cedar Park, Texas