FDA approves first ever ‘digital pill’

An innovative medical device, in the form of a pill containing a built-in sensor has been developed and been given approval, based on safety and efficacy data, by U.S. authorities.

by Tim Sandle

What is being heralded as the world’s first ‘digital’ pill has gained approved by the U.S. Food and Drug Administration (FDA). The pill is called Abilify MyCite. The pill contains a medication called aripiprazole, which treats conditions like schizophrenia, bipolar disorder and depression. Also combined with the pill is an ingestible sensor. The pill comes after several years of research and is a venture between the Japanese pharmaceutical company Otsuka and digital medicine service Proteus Digital Health.

It is the sensor that creates the ‘digital’ or ‘smart’ pill. The purpose of the sensor, according to The Verge, is to record when the pill has been taken. This happens by a signal being sent to a wearable patch (fixed to the left rib cage); and then from the patch to a mobile device such as a smartphone via Bluetooth. The patch has additional functionality. It records activity levels, sleeping patterns, steps taken, and heart rate. The patch needs to be replaced every seven days.

The purpose of this is to determine when a pill has been taken. This either acts as a reminder  to patients that they have (or to verify that they have not) taken their required dose of medication; or, for more serious cases where a patient has been sectioned as the result of a mental disorder, to enable medics to record the fact that a medication has been taken.

Failure to take medications has societal and economic consequences, such as putting a strain on the hospital system. According to Dr. William Shrank, chief medical officer of the health plan division at the University of Pittsburgh Medical Center, who spoke with the New York Times on this subject: “When patients don’t adhere to lifestyle or medications that are prescribed for them, there are really substantive consequences that are bad for the patient and very costly.”

The sensor is only the size of a grain of sand. It is manufactured from silicon, copper, and magnesium. In terms of how the sensor works, an electrical signal is activated when the sensor comes into contact with stomach acid.

It is a common problem with medications, either through forgetfulness or as a conscious act, when patients do not taken the medicines prescribed to them. The digital pill aims to redress this.

Commenting on the go-ahead for the digital pill to be marketed, Mitchell Mathis, who is the director of the Division of Psychiatry Products in the FDA, told PharmaPhorum: “Being able to track ingestion of medications prescribed for mental illness may be useful for some patients.”

The regulator added: “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”

The agreement relates to both parts of the smart medication: Abilify and Proteus Health’s sensor and patch, for the U.S. market. A label warning will accompany the product. This will state that the combined smart system has not been shown to improve patient compliance and that there are concerns about the effectiveness of the tracker in real-time since detection may be delayed. Nevertheless, the digital pill is likely to become popular with the medical establishment. The price of the pill has yet to be announced.

The Wall Street Journal opines that there could now be a raft of approval requests for other digital pills. The paper also notes that the FDA are preparing to hire more staff with understanding of software development in relation to medical devices.

Imagining a world without species

Categorizing species can get especially hazy at small, microbial scales. After all, the classical definition of species as interbreeding individuals with sexually viable offspring doesn't apply to asexual organisms. Examining shared DNA doesn't help either: collectively, E. coli bacteria have only 20 percent of genes in common. The classification process gets even trickier as many microbes work so closely that it is unclear what to call separate organisms, let alone separate species.

The woes of classification generate contentious debates in the biology community. But, for postdoctoral fellow Mikhail Tikhonov, one field's contentious debate is another's theoretical playground. In new research, he asks: Could organism interactions be described without mentioning species at all?

Key question: “how does evolution act on the structure within a community, rather than on a species?"

This question is not only interesting on a theoretical level, but could have real-world implications in understanding and treating human disease. While some diseases (like pneumonia or meningitis) have specific culprits, many others (like obesity or type II diabetes) seem to be associated to a community-level dysfunction of our microbiome -- the highly diverse bacterial communities that live on and inside our bodies. To understand these diseases, researchers must understand how the system works as a whole.

See:

Mikhail Tikhonov. Theoretical microbial ecology without species. Physical Review E, 2017; 96 (3) DOI: 10.1103/PhysRevE.96.032410

 Posted by Dr. Tim Sandle

Aggressive UTI bacteria hijack copper

Escherichia coli bacteria -- those at the root of hard-to-treat urinary tract infections (UTIs) -- hijack trace amounts of copper in the body and use it as a nutrient to fuel growth. This finding suggests blocking this system may starve E. coli infections, opening the door to treating UTIs using drugs that work differently from traditional antibiotics.

Copper is an essential mineral -- found in shellfish, whole grains, nuts, beans and other foods. It can kill pathogens in high concentrations. But it was unclear how E. coli handles copper ions present in urine, an extremely complex medium containing many trace metals and other compounds.

In past work studying strains of E. coli known to cause difficult-to-treat UTIs, the researchers showed that a molecule called yersiniabactin that is secreted by the bacteria sequesters copper, preventing it from accumulating to antibacterial levels. But what it does with this bound copper has been unknown.

While bacteria are known to bring iron -- another essential mineral -- into the cell, the researchers noted that E. coli have long been thought to lack a method to import copper. Indeed, scientists have assumed that yersiniabactin only imports iron.

In the new study, the researchers showed that yersiniabactin imports copper ions into the cell, where these charged particles help trigger the many biochemical reactions that bacteria require to grow and reproduce. The scientists further showed that once relieved of its mineral cargo, yersiniabactin goes back outside the cell to mop up more copper. The researchers dubbed this strategy "nutritional passivation." In metallurgy, passivation refers to treating or coating metal to make it less reactive.

The researchers also have shown that yersiniabactin can bind to a variety of metals beyond copper and iron, including nickel, cobalt and chromium.

See:

Eun-Ik Koh, Anne E Robinson, Nilantha Bandara, Buck E Rogers, Jeffrey P Henderson. Copper import in Escherichia coli by the yersiniabactin metallophore system. Nature Chemical Biology, 2017; DOI: 10.1038/nchembio.2441

Posted by Dr. Tim Sandle

Antibiotic Alternative Micreos wins Most Impactful Innovation

In the presence of former UN-Secretary-General Kofi Annan and Dutch minister Melanie Schultz of Infrastructure & the Environment, Micreos' alternative to antibiotics was chosen as the most impactful innovation of The Netherlands. Micreos will represent The Netherlands at the semi-finals of Ideas from Europe in Talinn, Estonia on November 22 2017.

Micreos' endolysin technology, enabling targeted killing of only unwanted bacteria - regardless of antibiotic resistance - was selected by a professional jury. Jury-chair Kasja Ollongren, Deputy mayor of Amsterdam, emphasized the impact Micreos' products can have for millions of people.


The Making Waves-conference was attended by hundreds of policy makers, entrepreneurs, investors and developers. Guest of honour, Kofi Annan, winner of the Nobel Peace Prize, said: "I am really excited about Micreos' alternative to antibiotics".


Kasja Ollongren: "We chose Micreos because the company's technology is already helping tens of thousands of people and we're convinced Micreos' alternative to antibiotics can be life-changing for millions."

Micreos CEO Mark Offerhaus: "Antibiotic-resistance is an enormous global problem. We are honoured with the recognition. Gladskin has already been life-changing for people suffering from inflammatory skin diseases such as eczema, acne, rosacea and wound infections caused or aggravated by the Staphylococcus aureus bacteria, including the resistant MRSA. But as far as we're concerned, this marks only the beginning. Our endolysin technology offers a real and sustainable alternative to antibiotics, the broad potential of this technology is immeasurable. There's no need to wait and no time to lose."

Posted by Dr. Tim Sandle

Thank you to Rapid Micro Biosystems

Rapid Micro Biosystems has been involved with the Pharmaceutical Microbiology Resources website and the Pharmaceutical Microbiology LinkedIn Group since the early days. These sites have helped to promote the concept of rapid microbiological methods and some of Rapid Micro Biosystems innovations.

Although the partnership has reached an end-point, I would like to thank Rapid Micro Biosystems for their support and sponsorship over the past six-years.



Posted by Dr. Tim Sandle

The future possibilities of graphene for microbiology

Graphene is the most widely researched new material. It is an allotrope of carbon and due to special properties the material is being tested out within the fields of consumer and medicinal electronics. While these applications have received considerable attention developments relating to microbiology are taking place. This short review article considers bacterial staining and anti-bacterial activity, as two of the most promising future developments.

An essay by Tim Sandle

Graphene is a material derived from carbon and it has unique physicochemical properties. Graphene is formed where graphite is taken and atom thick layers are sliced away. The resultant structure is a single-layer of carbon atoms linked in a hexagonal chicken-wire pattern. Within the structure each of the atoms share a cloud of electrons moving freely about the surface. The material is light, transparent, strong and very conductive (Allen et al, 2010). Compared to other carbon allotrope, such as fullerenes, carbon nanotubes and graphite, graphene exhibits many exceptional physical and chemical properties. Graphene related materials are of great interest in the field of biomedicines and applications are underway in biosensing and drug delivery.

Graphene as a Gram-stain alternative

New research, from the University of Illinois at Chicago, suggests that graphene can be used for performing Gram-stains, as part of microbial identification. A review of the properties of graphene shows it can detect variances to cell vibration when a cell comes into contact with the material. So far the tests undertaken with graphene have related to cancer. Here atomic vibration differs depending upon whether the cell is a cancer cell or a normal cell. This happens because the cancer cell’s hyperactivity leads to a higher negative charge, and this causes a higher level of protons to be released. This difference can be detected, helping medical technologists to identify cancerous growth.

Assessing the variances in vibration is possible using an established laboratory method called Raman spectroscopy (a spectroscopic technique used to observe vibrational, rotational, and other low-frequency modes in a system).

According to lead researcher Vikas Berry, who is the associate professor and head of chemical engineering, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine: “We may be able to use it with bacteria to quickly see if the strain is Gram-positive or Gram-negative…We may be able to use it to detect sickle cells.” Berry made this remark to Controlled Environments magazine (Anon, 2017).

In a parallel development, one research group have created a graphene sensor for Escherichia coli. This involved fabricating a flexible substrate onto which a sensor device with O-ring is fitted. Once contact takes place with the suspected organism, Raman spectra is used to indicate the presence (Basu et al, 2014).

As all microbiologists know, the Gram-stain is the key test for distinguishing between two groups of bacteria based on cell wall morphologies (Sandle, 2014). The Gram stain procedure distinguishes between Gram positive and Gram negative groups by coloring these cells red or violet. Gram staining is a common technique used to differentiate two large groups of bacteria based on their different cell wall constituents. The Gram stain procedure distinguishes between Gram positive and Gram negative groups by coloring these cells red or violet. Gram positive bacteria stain violet due to the presence of a thick layer of peptidoglycan in their cell walls, which retains the crystal violet these cells are stained with. Alternatively, Gram negative bacteria stain red, which is attributed to a thinner peptidoglycan wall, which does not retain the crystal violet during the decolouring process (Sandle, 2004).

While the Gram-stain technique is well described it is sometimes prone to error. This can relate to the types of organisms, the age of the cultures, or due to errors made by the person performing the test (such as over decoloursation). A method based on graphene would error proof. Whether such a method becomes commercially available will depend on development costs.

Graphene as an antibacterial agent

As well as using graphene as a potential diagnostic tool, graphene can also be used as an anti-bacterial measure (where liposome-embedded graphene reduces the growth capability of bacteria). Research by Zappacosta and colleagues showed that graphene aqueous dispersion is stable for several days and demonstrates significant antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains, with a reduction in the growth of S. aureus and E. coli as high as 60 and 78%, respectively.

In a similar application, researchers have looked at graphene-iodine nano-composites, formed via electrostatic interactions between positively charged graphene derivatives and triiodide anions, as anti-bacterial agents (Some et al, 2015). With this, the antibacterial potential of these graphene-iodine composites against Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirobilis, Staphylococcus aureus, and Escherichia coli has been demonstrated. The success against the organisms relates to the inherent cytotoxicity of the nanocomposite, specifically through electron transfer interaction from microbial membrane to graphene.

Furthermore, scientists are studying graphene oxide with the aim of creating bacteria-killing catheters and medical devices. Here coating surgical tools with this carbon-based compound could kill bacteria, reducing the need for antibiotics, decreasing the rates of post-operative infections and speeding recovery times. This is with graphene oxide, which is a form of graphene with molecular oxygen incorporated into it. This compound protects against infection by destroying bacteria before it gets inside the body. In terms of the process the graphene oxide wraps around the bacteria, puncturing its membrane. A broken membrane prevents the bacteria from growing and often kills it.

Studies conducted at the Università Cattolica del Sacro Cuore in Rome indicate that the compound is most effective when paired with salt. Getting the salt balance correct is important. With too little salt and then the graphene oxide is unable to wrap around the bacteria; and with  too much salt and the graphene aggregates, failing to puncture the bacteria's membrane. In order to destroy both Gram positive and Gram negative bacteria a 300 nanometer sheet of graphene oxide solution must be mixed with low molarity (<10 mM) calcium chloride is required (Anon, 2015).

Summary

These two related research strands (for differential microbiology and as an antibacterial agent) signal that graphene, the so-called ‘wonder material’ of our age, is set to make a significant impact upon microbiology. As with the development of any novel method, progress will be slow. However, the research results reported to date suggest that graphene is set to make a major contribution to microbiology.

References

Allen, M. J., Tung, V.C. and R. B. Kaner, R.B. Honeycomb carbon: a review of graphene, Chem. Rev., 2010, 110, 132

Anon. Biophysical Society report “Towards a “green” antimicrobial therapy: Study of graphene nanosheets interaction with human pathogens”, 2015 (http://tinyurl.com/zzgsofu)

Anon. First Use of Graphene to Find Cancer Cells, Controlled Environments, 2017 (http://www.cemag.us/news/2017/02/first-use-graphene-find-cancer-cells)

Basu, P.K., Indukuri, D., Keshavan, S., Bhat, N. (2014) Graphene based E. coli sensor on flexible acetate sheet, Sensors and Actuators B Chemical 190:342-347 (https://www.researchgate.net/publication/256926101_Graphene_based_E_coli_sensor_on_flexible_acetate_sheet)

Sandle, T. (2004) Gram’s Stain: History and Explanation of the Fundamental Technique of Determinative Bacteriology’, IST Science and Technology, No. 54, pp3-4

Sandle, T. (2014). ‘Microbial Identification: Laboratory Techniques and Methods. In Chesca, A. (Ed.) Methods for Diseases: Diagnostic with Applicability in Practice, Lambert Academic Publishing, Germany, pp15-26

Some, S., Sohm, J., Kim, J. et al Graphene-Iodine Nanocomposites: Highly Potent Bacterial Inhibitors that are Bio-compatible with Human Cells, Scientific Reports 6, Article number: 20015 (2016). doi:10.1038/srep20015

Zappacosta, R., Di Giulio, M., Ettorre, V. et al Liposome-induced exfoliation of graphite to few-layer graphene dispersion with antibacterial activity, J. Mater. Chem. B, 2015, 3, 6520-6527 (http://pubs.rsc.org/en/content/articlehtml/2015/tb/c5tb00798d)

by Dr. Tim Sandle

EDQM: Microbiological control symposium

A symposium on microbiology in the pharmaceutical sector was the opportunity for the EDQM to gather feedback from users of the European Pharmacopoeia on alternative testing methods for microbiological control and sterilisation processes. The event, which took place in Strasbourg on 10-11 October 2017, was attended by a wide range of experts in the pharmaceutical and microbiological fields who reviewed the latest trends and innovations in the field of microbiology, in addition to Pharmacopoeial approaches and related regulatory requirements.

Over recent years, the European Pharmacopoeia has given pharmaceutical manufacturers access to new chapters for microbiological control, kick-starting a new era for the world of microbiology and rendering the uptake of modern microbiological methods an evolution already in process, rather than a revolution.

Among the topics covered was the use of modern methods for microbiological control, with specific sessions focusing on sterilisation and biological indicators, rapid microbiological methods and control methods for cell therapy products and pharmaceutical water. Reports on successful new methods gave an overview of the potential benefits in terms of costs and time efficiency and, most importantly, in terms of quality. Authorities, manufacturers and suppliers of new technologies also discussed the current acceptance of these new methods at a regulatory level across the world. Over recent years, the European Pharmacopoeia has given pharmaceutical manufacturers access to new chapters for microbiological control, kick-starting a new era for the world of microbiology and rendering the uptake of modern microbiological methods an evolution already in process, rather than a revolution.

Various chapters of the European Pharmacopoeia have laid the foundations for the use of modern methods for microbiological control and have been available for more than ten years – notably 5.1.6. Alternative methods for control of microbiological quality, 2.6.7. Mycoplasmas, 2.6.12. Microbiological examination of non-sterile products: microbial enumeration tests and 2.6.27. Microbiological examination of cell-based preparations. Chapter 5.1.6 in particular was recently further revised to take into full account the latest technological developments and to provide clear guidance for validating alternative microbiological methods.

Interventions to influence antibiotic prescribing behavior

A new review, ‘Clinician-targeted interventions to influence antibiotic prescribing behaviour for acute respiratory infections in primary care’ published on September 7, 2017 in the Cochrane Database of Systematic Reviews.

An overview of this important review is also available.

Recent Cochrane Reviews:

Whole grain cereals for the primary or secondary prevention of cardiovascular disease
Antibiotics for persistent cough or wheeze following acute bronchiolitis in children
Interventions for emergency contraception

Cochrane is a global independent network of researchers, professionals, patients, carers and people interested in health. Cochrane produces reviews which study all of the best available evidence generated through research and make it easier to inform decisions about health. These are called systematic reviews.

Cochrane is a not-for profit organization with collaborators from more than 120 countries working together to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. Our work is recognized as representing an international gold standard for high quality, trusted information.

Posted by Dr. Tim Sandle

What the FDA Guidance on Data Integrity Means for Your Lab

Dale Curtis Jr. is the President of Astrix Technology Group has written a review of data integrity requirements for the laboratory. Here is an extract:

“Data integrity is the maintenance and assurance of the accuracy and consistency of data over its entire life-cycle. With regards to pharmaceutical manufacturing, the FDA expects that all data submitted to the agency in an effort to gain drug approval is complete, consistent and accurate. Data integrity is a fundamental principle in pharmaceutical manufacturing that enables traceability of a batch back to its origin and thereby ensures that drugs are made and tested according to required quality standards.”

The paper can be found here: Data Integrity

Special book offer for readers:

Posted by Dr. Tim Sandle

Pharmaceutical Microbiology Book

Pharmaceutical Microbiology

Pharmaceutical Microbiology: Essentials for Quality Assurance and Quality Control presents that latest information on protecting pharmaceutical and healthcare products from spoilage by microorganisms, and protecting patients and consumers. With both sterile and non-sterile products, the effects can range from discoloration to the potential for fatality.

The book provides an overview of the function of the pharmaceutical microbiologist and what they need to know, from regulatory filing and GMP, to laboratory design and management, and compendia tests and risk assessment tools and techniques. These key aspects are discussed through a series of dedicated chapters, with topics covering auditing, validation, data analysis, bioburden, toxins, microbial identification, culture media, and contamination control.

- Contains the applications of pharmaceutical microbiology in sterile and non-sterile products
- Presents the practical aspects of pharmaceutical microbiology testing
- Provides contamination control risks and remediation strategies, along with rapid microbiological methods
- Includes bioburden, endotoxin, and specific microbial risks
- Highlights relevant case studies and risk assessment scenarios

Title Index:

- Chapter 1: Introduction to Pharmaceutical Microbiology
- Chapter 2: Microbiology and Pharmaceuticals
- Chapter 3: GMP, regulations and standards
- Chapter 4: Laboratory management and design
- Chapter 5: Microbiological culture media
- Chapter 6: Basic microbiological laboratory techniques
- Chapter 7: Bioburden testing
- Chapter 8: Assessment of raw materials
- Chapter 9: Microbial identification
- Chapter 10: Assessment of pharmaceutical water systems
- Chapter 11: Endotoxin and pyrogen testing
- Chapter 12: Sterilisation and sterility assurance
- Chapter 13: Biological indicators
- Chapter 14: Antibiotic effectiveness testing and preservative efficacy testing
- Chapter 15: Disinfection
- Chapter 16: Cleanroom microbiology and contamination control
- Chapter 17: Rapid microbiological methods
- Chapter 18: Risk assessment and microbiology
- Chapter 19: Manufacturing and validation
- Chapter 20: Microbiological batch review
- Chapter 21: Microbiological audits
- Chapter 22: Microbial Challenges in the Pharmaceutical Industry
- Conclusion

See below:



Or order from Elsevier.

Posted by Dr. Tim Sandle

Theory and Practice of Disease Diagnosis

A new book of interest:

The book provides theoretical and practical information for diseases diagnosis. It is a collaborative book to support IP Erasmus project MDHP, with partners from different countries from Europe. Thebook includes chapters by Professor Ilya Azizov, from Karaganda State Medical University, Kazakhstan, now Smolensk State Medical University, Russia, and Dr. Antonella Chesca and Dr. Tim Sandle.

The book has been written with support for professors and researches from prestigious universities.

Reference:

Chesca, A., Cengiz, M. and Sandle, T. (Eds.) Theory and Practice of Disease Diagnosis, LAP LAMBERT Academic Publishing, Germany, ISBN-13: 978-3330084384

For details see: Amazon UK or LAP Publishing

Posted by Dr. Tim Sandle

50+ FDA acronyms that matter to your business

The Vaisala Measurement & Monitoring Program is offering a list of useful FDA acronyms. For further details see: Vaisala.

An Introduction To Environmental Monitoring & Cleaning For Aseptic Environments

Crystal Booth has written a useful article for Pharmaceutical Online looking at environmental monitoring and disinfection of aseptic processing environments. Here is an extract:

“Microbial control is critical in cleanroom environments. Contaminated environments can lead to product recalls, regulatory observations, fines, or even consumer deaths. To prevent, destroy, and monitor microbial contamination in cleanrooms, several aspects of cleanroom microbiology must be understood. This foundational introduction to cleanroom microbiology article series discusses some of those aspects. Parts 1 and 2 introduced cleanroom microbiology, discussed guidance documents and FDA observations, and summarized common sources of microbial contamination in cleanrooms. Part 3 provided an overview of cleanroom gowning procedures. This final article will address concepts of environmental monitoring and the importance of disinfectant efficacy and proper cleaning.”

The full article can be found here: Pharmaceutical Online

Posted by Dr. Tim Sandle

Bacterial in-fighting provides new treatment for hospital infections

A bacteria that is a leading cause of death worldwide from hospital acquired infections following antibiotic treatment looks set to be brought down through its own sibling rivalry. New research from the University of Sheffield shows that Different strains of Clostridium difficile (C. diff) use tiny weapons to kill each other, and scientists from the UK and US have discovered how these work, enabling them to be engineered into an antimicrobial agent with the potential to prevent or cure C. diff infection.

Further study has shown when C. diff develops a resistance to these weapons, the bacteria can no longer cause infection, making them harmless. Like many bacteria, C. diff can make a weapon that is able to identify and kill competing C. diff strains. This weapon attaches to the surface of other C. diff cells and fires a harpoon-type needle through their membrane, causing the cell to die. The researchers have managed to engineer this weapon so that it can be mass produced in a stable form as a potential treatment or preventative for C. diff infections.

See:

Joseph A. Kirk, Dana Gebhart, Anthony M. Buckley, Stephen Lok, Dean Scholl, Gillian R. Douce, Gregory R. Govoni, Robert P. Fagan. New class of precision antimicrobials redefines role of Clostridium difficile S-layer in virulence and viability. Science Translational Medicine, 2017; 9 (406): eaah6813 DOI: 10.1126/scitranslmed.aah6813

Posted by Dr. Tim Sandle

Cilia: 'The bouncer' of bacteria

A new paper, from University of Southern California, elucidates the active role of cilia in regulating flow for bacteria filtering and enhancing chemical communication.

The paper, published in the Proceedings of the National Academy of Sciences, describes a framework for the role of fluid mechanics in letting symbiotic bacteria in an organism and enhancing chemical communication between the symbiont and the host organism. The results are contrary to previous research which assumes that cilia solely play a "clearance function." They could shed light on the role cilia -- which are the size of one hundredth of a single human hair -- play in human respiratory system and even in the reproductive systems and the brain. Their findings could also provide insights on how cilia dysfunction within organs affect for example, pulmonary conditions or infertility (how cilia help sperm reach eggs).

To learn about how cilia might work in the human body, Kanso, in collaboration with symbiosis expert McFall-Ngai and biofluid expert Janna Nawroth studied bobtail squid. The researchers examined how these squids in their nascent stage allow symbiotic bacteria Vibrio Fischeri to enter into their ciliated light organs, which play a crucial role in camouflaging the ink sacks of the otherwise translucent organism while they hunt for food at night. The scholars sought to know: why does this bacterium gain access and why do all bacteria fail to accumulate within the squid's light organ? In addition, they sought to explain what, if any, is the role of cilia in allowing access?

Researchers discovered that a vortical or "donut-like" flow generated by the cilia was kicking away most particles. The role of the fluid motion in filtering particles by size was verified using a physics-based mathematical model. One of the core findings was that there were two distinct flows taking place by two different types of cilia. Longer cilia move in a "wave-like" fashion which creates a vortical flow field that filters particles and then shorter cilia which beat randomly keep the particles in place and gently mix the local flow. This random motion by the cilia and fluid mixing enhance the chemical screening of bacteria. To further prove the important role played by cilia, the researchers also found that if cilia are "killed," particles will accumulate everywhere in the organism.

See:

Janna C. Nawroth, Hanliang Guo, Eric Koch, Elizabeth A. C. Heath-Heckman, John C. Hermanson, Edward G. Ruby, John O. Dabiri, Eva Kanso, Margaret McFall-Ngai. Motile cilia create fluid-mechanical microhabitats for the active recruitment of the host microbiome. Proceedings of the National Academy of Sciences, 2017; 114 (36): 9510 DOI: 10.1073/pnas.1706926114

Posted by Dr. Tim Sandle