Martha Clokie

Last updated
Martha Clokie
Born
Martha Rebecca Jane Clokie
Alma mater University of Dundee (BSc)
University of Edinburgh (MSc)
University of Leicester (PhD)
Scientific career
Fields Microbiology
Institutions University of Leicester
Scripps Institution of Oceanography
University of Warwick
Thesis Molecular studies of Southern Hemisphere disjunction in three plant genera, Eucryphia, Griselinia and Coriaria  (2001)
Website www2.le.ac.uk/departments/genetics/people/martha-clokie

Martha Rebecca Jane Clokie is a Professor of Microbiology at the University of Leicester. [1] Her research investigates the identification and development of bacteriophages that kill pathogens in an effort to develop new antimicrobials. [2]

Contents

Education

Clokie studied biology at the University of Dundee. [3] She graduated in 1996 and moved to Edinburgh, where she started a postgraduate degree in biodiversity. [3] She earned a master's degree at the University of Edinburgh in 1997 and moved to Leicester. Clokie earned her doctoral degree in molecular ecology at the University of Leicester in 2001 [4] for research on the evolution of three genera of plants: Eucryphia , Griselinia and Coriaria . [3]

Research and career

After her PhD, Clokie was a postdoctoral researcher at the University of Warwick and the Scripps Institution of Oceanography. [3] Clokie started her research career investigating the molecular evolution of plants. [5]

Clokie joined the University of Leicester as a lecturer in 2007 and was promoted to Professor in 2016. [3] [1] She is interested in viruses known as bacteriophages which can be used to treat disease. Her work involves cyanobacteria and the sequencing of various bacteriophages. [6] She demonstrated that marine phages contain the genes responsible for photosynthesis, and that phages do not only exert pressure on the infection-survival mechanism of cyanobacteria but can acquire the genes of a bacteria's prey. [5]

Her research includes identifying specific phage combinations that can be used to destroy Clostridioides difficile Infections (CDI) while maintaining a healthy gut. [7] [8] CDI causes almost two fifths of diarrhoea associated with antibiotics in the Western world, and one in ten of patients die due to a lack of effective treatment. [7] [9] The bacteriophage could reduce the growth of C. difficile and simultaneously defend beneficial bacterial that are typically destroyed by antibiotics. [7] The bacteriophages can be delivered orally and result in destruction of C. difficile within two days. [7] [10] Clokie went on to demonstrate that C. difficile can evolve into a new species, with a specific strand that is adapted to spread quickly in hospitals. [11] The new species survives on the sugar-rich diets of Westerners and can evade common disinfectants. [11]

She has also worked on bacteriophages that can be used to prevent bacterial infections in Antheraea assamensis (Muga silkworms). [12] Muga silk is produced in Assam and is one of the most valuable silks in the world. They are at risk from Flacherie, a bacterial disease that is caused by larvae eating infected leaves. [12] Alongside working on silk worms, Clokie has explored the use of phages in the treatment of drug resistant urinary tract infections. She has shown that bacteriophages could be used to treat bacterial disease in pigs. [13] [14] These phages disable the Salmonella bacterial disease that infects pigs and can be added to pig feed. [14]

Clokie maintained bacteriophages were helping growing numbers of patients in compassionate use cases and could become routine for conditions like chronic UTIs and diabetic foot ulcers. Clokie stated “The risk from antibiotic resistance is dire and getting worse … I find it really shocking. Unless we have clinical trials, phages won’t become mainstream as a medicine, and that’s where we’re aiming.(...) I get fairly regular emails from doctors and patients wanting phages. Doctors have gone from being completely disinterested to ‘give me the phages now’ (…) There are people who need phages now because they’re dying.” [15]

Selected publications

Her publications include;

Clokie is founding editor-in-chief of the journal PHAGE: Therapy, Applications and Research. [20]

Awards and honours

Clokie was awarded a Grand Challenges exploration fund award from the Bill & Melinda Gates Foundation. [21] This allowed her to investigate bacteriophages that could be used to eradicate Shigellosis. [21] In 2019 Clokie was interviewed on the BBC Radio 4 programme The Life Scientific . [22]

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<span class="mw-page-title-main">Prophage</span>

A prophage is a bacteriophage genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is the characteristic step of the lysogenic cycle of temperate phages. Prophages remain latent in the genome through multiple cell divisions until activation by an external factor, such as UV light, leading to production of new phage particles that will lyse the cell and spread. As ubiquitous mobile genetic elements, prophages play important roles in bacterial genetics and evolution, such as in the acquisition of virulence factors.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

Clostridioides difficile infection , also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.

<span class="mw-page-title-main">Phage therapy</span> Therapeutic use of bacteriophages to treat bacterial infections

Phage therapy, viral phage therapy, or phagotherapy is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections. This therapeutic approach emerged at the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the Second World War. Bacteriophages, known as phages, are a form of virus that attach to bacterial cells and inject their genome into the cell. The bacteria's production of the viral genome interferes with its ability to function, halting the bacterial infection. The bacterial cell causing the infection is unable to reproduce and instead produces additional phages. Phages are very selective in the strains of bacteria they are effective against.

<span class="mw-page-title-main">Lysogenic cycle</span> Process of virus reproduction

Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction. Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a circular replicon in the bacterial cytoplasm. In this condition the bacterium continues to live and reproduce normally, while the bacteriophage lies in a dormant state in the host cell. The genetic material of the bacteriophage, called a prophage, can be transmitted to daughter cells at each subsequent cell division, and later events can release it, causing proliferation of new phages via the lytic cycle. Lysogenic cycles can also occur in eukaryotes, although the method of DNA incorporation is not fully understood. For instance the AIDS viruses can either infect humans lytically, or lay dormant (lysogenic) as part of the infected cells' genome, keeping the ability to return to lysis at a later time. The rest of this article is about lysogeny in bacterial hosts.

<span class="mw-page-title-main">Fecal microbiota transplant</span> Process of transplantation of fecal bacteria from a healthy individual into a recipient

Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.

Bacteriophage (phage) are viruses of bacteria and arguably are the most numerous "organisms" on Earth. The history of phage study is captured, in part, in the books published on the topic. This is a list of over 100 monographs on or related to phages.

<span class="mw-page-title-main">Cyanophage</span> Virus that infects cyanobacteria

Cyanophages are viruses that infect cyanobacteria, also known as Cyanophyta or blue-green algae. Cyanobacteria are a phylum of bacteria that obtain their energy through the process of photosynthesis. Although cyanobacteria metabolize photoautotrophically like eukaryotic plants, they have prokaryotic cell structure. Cyanophages can be found in both freshwater and marine environments. Marine and freshwater cyanophages have icosahedral heads, which contain double-stranded DNA, attached to a tail by connector proteins. The size of the head and tail vary among species of cyanophages. Cyanophages infect a wide range of cyanobacteria and are key regulators of the cyanobacterial populations in aquatic environments, and may aid in the prevention of cyanobacterial blooms in freshwater and marine ecosystems. These blooms can pose a danger to humans and other animals, particularly in eutrophic freshwater lakes. Infection by these viruses is highly prevalent in cells belonging to Synechococcus spp. in marine environments, where up to 5% of cells belonging to marine cyanobacterial cells have been reported to contain mature phage particles.

In biology, a pathogen in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

<span class="mw-page-title-main">Enzybiotics</span>

Enzybiotics are an experimental antibacterial therapy first described by Nelson, Loomis, and Fischetti. The term is derived from a combination of the words “enzyme” and “antibiotics.” Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance, which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as C. difficile, or C. diff, is Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase (CDT). Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

Cyanophage N-1 is a myovirus bacteriophage that infects freshwater filamentous cyanobacteria of the Nostoc genus. The virus was first isolated by Kenneth Adolph and Robert Haselkorn in 1971 in the US, from the nitrogen-fixing cyanobacterium, Nostoc muscorum. N-1 is closely related to cyanophage A-1, but only distantly to other cyanophages of freshwater or marine origin.

Auxiliary metabolic genes (AMGs) are found in many bacteriophages but originated in bacterial cells. AMGs modulate host cell metabolism during infection so that the phage can replicate more efficiently. For instance, bacteriophages that infect the abundant marine cyanobacteria Synechococcus and Prochlorococcus (cyanophages) carry AMGs that have been acquired from their immediate host as well as more distantly-related bacteria. Cyanophage AMGs support a variety of functions including photosynthesis, carbon metabolism, nucleic acid synthesis and metabolism.

<span class="mw-page-title-main">Center for Innovative Phage Applications and Therapeutics</span> Phage therapy center in San Diego, CA, US

The Center for Innovative Phage Applications and Therapeutics (IPATH) is the first phage therapy center in North America, founded in the UC San Diego School of Medicine in June 2018, with seed funding from UC San Diego Chancellor Pradeep Khosla. The center was founded by Steffanie A. Strathdee and Robert "Chip" Schooley, both professors at UC San Diego School of Medicine. The center currently treats patients with life-threatening multi-drug resistant infections with phage therapy, on a case-by-case basis, through the Food and Drug Administration's (FDA's) compassionate use program. IPATH aims to initiate phase I/II phage therapy clinical trials, focusing on patients with cystic fibrosis and infections related to implantable hardware, such as pacemakers and prosthetic joints. The first planned clinical trial is set to look at otherwise healthy cystic fibrosis patients that are shedding Pseudomonas aeruginosa.

<span class="mw-page-title-main">Robert T. Schooley</span> American infectious disease physician

Robert "Chip" T. Schooley is an American infectious disease physician, who is the Vice Chair of Academic Affairs, Senior Director of International Initiatives, and Co-Director at the Center for Innovative Phage Applications and Therapeutics (IPATH), at the University of California San Diego School of Medicine. He is an expert in HIV and hepatitis C (HCV) infection and treatment, and in 2016, was the first physician to treat a patient in the United States with intravenous bacteriophage therapy for a systemic bacterial infection.

Arbitrium is a viral peptide produced by bacteriophages to communicate with each other. It is six amino acids long, and is produced when a phage infects a bacterial host. It signals to other phages that a host has been infected.

<span class="mw-page-title-main">Heather Hendrickson</span> American-born New Zealand-based microbiologist

Heather Hendrickson is a microbiologist and a Senior Lecturer in the School of Biological Sciences at the University of Canterbury in Christchurch, New Zealand. She previously worked at Massey University, Auckland, New Zealand. Her research is focussed on the evolution of bacterial cell shape, and the discovery of bacteriophages that can attack antibiotic-resistant bacteria and the bee disease American foulbrood.

<span class="mw-page-title-main">Multidrug-resistant bacteria</span>

Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.

Vincent A. Fischetti is a world renowned American microbiologist and immunologist. He is Professor of and Head of the Laboratory of Bacterial Pathogenesis and Immunology at Rockefeller University in New York City. His primary areas of research are bacterial pathogenesis, bacterial genomics, immunology, virology, microbiology, and therapeutics. He was the first scientist to clone and sequence a surface protein on gram-positive bacteria, the M protein from S. pyogenes, and determine its unique coiled-coil structure. He also was the first use phage lysins as a therapeutic and an effective alternative to conventional antibiotics.

References

  1. 1 2 rjs29. "Professor Martha Clokie". le.ac.uk. University of Leicester. Retrieved 2019-11-16.
  2. ↑ Martha Clokie publications from Europe PubMed Central
  3. 1 2 3 4 5 "Martha Clokie". kisacoresearch.com. Kisaco Research. Retrieved 2019-11-16.
  4. ↑ Clokie, Martha Rebecca Jane (2001). Molecular studies of Southern Hemisphere disjunction in three plant genera, Eucryphia, Griselinia and Coriaria. figshare.com (PhD thesis). University of Leicester. hdl:2381/29823. OCLC   1063547917. EThOS   uk.bl.ethos.696943. Lock-green.svg
  5. 1 2 "Phage Therapy: Turning the Tables on Bacteria". genengnews.com. GEN - Genetic Engineering and Biotechnology News. 2019-03-06. Retrieved 2019-11-16.
  6. ↑ aijh1. "Martha Clokie". le.ac.uk. University of Leicester. Retrieved 2019-11-16.
  7. 1 2 3 4 ap507. "Bacteriophage cocktail shows significant promise for Clostridium difficile infections". le.ac.uk. University of Leicester. Retrieved 2019-11-16.
  8. ↑ Singh, Maanvi (18 October 2013). "Why Scientists Are Trying Viruses To Beat Back Bacteria". NPR.org. Retrieved 2019-11-16.
  9. ↑ "Scientists identify novel approach for bacteriophage treatment of CDI". sciencedaily.com. Retrieved 2019-11-16.
  10. ↑ Nale, Janet Y.; Spencer, Janice; Hargreaves, Katherine R.; Buckley, Anthony M.; Trzepiński, Przemysław; Douce, Gillian R.; Clokie, Martha R. J. (2015). "Bacteriophage Combinations Significantly Reduce Clostridium difficile GrowthIn Vitroand ProliferationIn Vivo". Antimicrobial Agents and Chemotherapy. 60 (2): 968–981. doi:10.1128/aac.01774-15. ISSN   0066-4804. PMC   4750681 . PMID   26643348.
  11. 1 2 "Diarrhea-causing bacteria adapted to spread in hospitals". sciencedaily.com. Retrieved 2019-11-16.
  12. 1 2 ap507. "University of Leicester research to 'save the most valuable silk moth in the world' — University of Leicester". le.ac.uk. Retrieved 2019-11-16.
  13. ↑ "A breakthrough to defuse the antibiotic time bomb?". pig-world.co.uk. Pig World. Retrieved 2019-11-16.
  14. 1 2 Ghosh, Pallab (2017-06-08). "Therapy could stop superbugs on farms" . Retrieved 2019-11-16.
  15. ↑ Bacteria-killing viruses could combat antibiotic resistance, says UK scientist The Guardian
  16. ↑ Clokie, Martha (2009). Bacteriophages: Methods and Protocols. Springer Protocols. ISBN   978-1-60327-564-4.
  17. ↑ Clokie, Martha R. J. (2011). "Phages in nature". Bacteriophage. 1 (1): 31–45. doi:10.4161/bact.1.1.14942. PMC   3109452 . PMID   21687533.
  18. ↑ Clokie, Martha R. J. (2006). "Marine cyanophages and light". Environmental Microbiology. 8 (12): 2074–2082. doi:10.1111/j.1462-2920.2006.01171.x. PMID   17107549.
  19. ↑ Mann, Nicholas H.; Cook, Annabel; Millard, Andrew; Bailey, Shaun; Clokie, Martha (2003). "Bacterial photosynthesis genes in a virus". Nature. 424 (6950): 741. doi: 10.1038/424741a . ISSN   0028-0836. PMID   12917674. Closed Access logo transparent.svg
  20. ↑ "PHAGE | Mary Ann Liebert, Inc., publishers". home.liebertpub.com. Retrieved 2019-11-16.
  21. 1 2 ap507. "University of Leicester receives funding for groundbreaking research in global health and development — University of Leicester". le.ac.uk. Retrieved 2019-11-16.
  22. ↑ "BBC Radio 4 - The Life Scientific, Martha Clokie on the viruses that could improve our health". BBC. Retrieved 2019-11-16.
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