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Archive for the ‘Microbiology’ Category

Penicillin: the accident that saved many lives

Fleming in his Lab - Photo. Date: 1881 - 1955
Alexander Fleming in his laboratory, 1881 – 1955

 

There have been many happy accidents in science. Several of these were of great benefit to medicine.

For example, in 1895, a German physicist working with a cathode ray tube happened to place his hand in front of the rays and found that he could see his bones in the image projected onto the screen. Soon after that, the first X-ray images were produced.

There have been other instances where serendipity played a role in unearthing effective treatments against diseases. 

 

THE FIND OF THE 20TH CENTURY

The most famous of these happy accidents is the discovery of Penicillin as an antibiotic remedy. 

Alexander Fleming, a Scottish bacteriologist, worked at the inoculations department at St Mary’s Hospital in the early 1900s. 

In September 1928, Fleming had left a pile of bacteria cultures in his laboratory before going on holiday with his family. The cultures he was studying were known to cause septic infections. By accident, he left one of the Petri dishes uncovered.

Fleming returned to find that a bluish-green mold, similar to the mold found on bread, had contaminated the specimen. The area around the mold in the Petri dish was clear of bacteria. 

Fleming observed that the mold seemed to have killed the germs. This mold was identified as a strain of Penicillium. He saw this as a potential treatment for bacterial infections. 

Penicillin culture,1929
Penicillin culture, 1929

 

IMPORTANCE OF SHARED SCIENCE

Fleming was able to further identify that it wasn’t just the mold that killed the bacteria but the ‘juice’ the mold seemed to produce. 

He also discovered that the ‘mold juice‘ was effective against pathogens that are responsible for diseases like Meningitis, Diphtheria and Gonorrhea. 

Fleming’s effort would bear no further fruits. He was not able to produce and purify the ‘mold juice’ in substantial quantities.

However, he named the substance Penicillin and published his findings in the British Journal of Experimental Pathology in 1929. This crucial step allowed others to build on his work.

A decade later, Fleming’s findings piqued the interest of two Oxford scientists: Howard Florey and Ernst Chain. Eventually, they found a way to mass-produce the antibiotic in a form that could kill harmful bacteria without having any toxic effects on the human body.

Vintage vials of Penicillin G
Vintage vials of Penicillin G

 

PENICILLIN’S WARTIME VALUE

During World War I, Alexander Fleming was stationed in France and served in the Army Medical Corps as a captain. He observed that the death of soldiers was not always from wounds inflicted in battle, but rather from bacterial infections.

The principal treatment of such infections consisted of the administration of antiseptics. Fleming noted that these often did more harm than good. He wrote about this, however, his findings were not taken seriously at the time.

During World War I, the death rate from bacterial pneumonia was 18%. In WWII, thanks to Penicillin, the death rate from the same condition fell to less than 1%. This enabled many soldiers to return home in good health.

 

AN EXCEPTIONAL DISCOVERY

The mass production of Penicillin is credited with saving the lives of many thousands of soldiers during World War II. 

Antibiotics of the Penicillin family have been found to cure a wide variety of bacterial infections from mild, moderate upper respiratory tract infections to skin ulcers and urinary tract infections.

In 1944, Alexander Fleming was knighted by King George VI. In 1945, he received a Nobel Prize in Physiology or Medicine, together with Howard Florey and Ernst Boris Chain. 

The praise was well deserved, as infections that were once life-threatening are now only mild inconveniences because of Penicillin’s versatility and efficacy. Penicillin richly deserves its place as one of the most important anti-infective drugs of all time.

Interestingly, Fleming was not the first to observe the antibacterial effect of Penicillium. Between 1868 and 1873, a famous surgeon named Theodor Billroth discovered that it inhibited bacterial growth – but nothing was done about it at the time. He died when Fleming was 13 years old.

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Learn more: GIDEON Guide to Antimicrobial Agents

Leeuwenhoek: scientist who saw ‘animalcules’

Anthony van Leeuwenhoek and animalcules drawings
Antonie van Leeuwenhoek and a drawing of animalcules

 

Some discover their aptitude for science by natural curiosity, which causes them to investigate their surroundings. In doing so they find many hidden secrets that only curiosity like theirs could have revealed. However, an inquisitive nature alone doesn’t make one a scientist. Explorers, adventurers, reporters, and criminal investigators all lead lives based on it too.

Something special happens when curiosity is coupled with an empirical mind. That combination begins to approach the scientific method. The only thing left is to provide a record of findings so that other scientists can attempt to falsify the results.

 

Scientist By Nature

Antonie van Leeuwenhoek did all of this and more. He used the scientific method to unearth the existence of previously unseen organisms, and he was in regular correspondence with the Royal Society in London, discussing his findings.

Leeuwenhoek was a businessman by trade, but a scientist by nature. His skill in grinding glass allowed him to produce single-lens microscopes that could magnify over 200 times. 

On 17th September 1683, Leeuwenhoek was the first to report the existence of bacteria seen through his microscopes. He called them little “animalcules”.

He achieved clearer and brighter images than any of his scientific fellows would achieve for centuries. This led to doubts and questions about the certainty of what he claimed to have seen.

It wasn’t until 1981 that Leeuwenhoek’s original specimens at the Royal Society were successfully photographed. Even this was done using one of his surviving microscopes. This finally dispelled the lingering disbelief that he indeed saw what he claimed. 

 

The Father Of Microbiology

Leeuwenhoek had 112 of his 200 letters published in the journal of the Royal Society. He was one of the journal’s most prolific writers, touching on many aspects of biology and even mineralogy. 

However, Leeuwenhoek’s greatest delights and findings were in the field of microbiology. His discoveries are still informing the discipline and being proven true today, especially his reports on bacteria.

 

The Importance of Bacteria

The world is now very aware of the presence and importance of bacteria. Some bacteria can be harmful, but most are beneficial.

We know that bacteria are used to treat some of the foods we love like yogurt and cheese. We know about the use of bacteria for preserving foods in fermentation and pickling. 

However, we also know bacteria are responsible for food spoilage or poisoning in some cases. Pathogenic bacteria may be transmitted in some foods which can cause food poisoning. For example, the CDC warns that soft cheeses made with unpasteurized milk carry a greater risk of causing a Listeria infection.

The importance of bacteria to humans is also seen in medicine and other industries. Bacterial infections and antibiotic remedies are now well known but bacteria have been put to use for a host of other purposes, such as microbial leaching of precious metals in mining.

 

Real-life data for microbiology studies

Just like Leeuwenhoek, modern students of microbiology can use real-life data. Lecturers like Dr. Monika Oli teach microbiology students using GIDEON because of its vast dataset and a versatile toolkit. She knows it gives meaningful context to their studies.

At the time of writing, the GIDEON database includes 1,766 pathogenic bacteria, 154 mycobacteria, and 130 yeasts and algae. And the database is updated daily! 

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Streptomyces – the smell of life

The Mall in Central Park, New York City in late autumn on rainy day
The Mall in Central Park, New York City in late autumn on a rainy day

 

Did you know that humans can detect the smell of wet soil 200,000 times better than sharks sense blood? [1] It appears our olfactory abilities are not that bad after all, at least when it comes to finding potential sources of food. Petrichor, the term to describe the scent was coined in 1964, by scientists I. Bear and R.G. Thomas, meaning “petros” – stone and “ichor” – the blood of the gods [2] in Greek.

Divine or not, Streptomyces is a genus of over 800 bacterial species and subspecies responsible for the earthy smell of Autumn we know and love. But could it be that our innate senses are drawn to wet dirt for more reasons than farming? 

 

Could eating dirt cure the plague?

That is yet to be tested, but Streptomyces are certainly fit for more purposes than poetic walks after the rain. They are the most important source of antibiotics [3].

What is an antibiotic? By definition, it is a substance produced by one organism that is capable of inhibiting the growth or destroying other organisms  – a direct translation from Greek would be ‘anti-life’. In nature, this yields Streptomyces a competitive advantage. Astonishingly, they are responsible for nearly two-thirds of natural antibiotics [4].

For instance, Streptomyces griseus produces Streptomycin, the first antibiotic against tuberculosis, and a drug of choice against the agent of Plague Yersinia pestis, along with other 28 pathogenic bacteria species [5].  Streptomyces avermitilis helps keep parasites in check with its potent avermectins, and Chloramphenicol – a drug effective against 92 pathogens, is produced by Streptomyces venezuelae.

Streptomyces glaucescens under a microscope
Image of Streptomyces glaucescens. Courtesy of Tobias Kieser, John Innes Centre

 

Mavericks of the Streptomyces family

Although these species are not considered to be important agents of infection, it is worth noting that not all Streptomyces bacteria are friends of humanity, however. Two rebels, Streptomyces somaliensis and Streptomyces sudanensis go against the grain by infecting people’s feet with actinomycotic mycetoma.

First described as ‘Madura foot’ in 1842, the disease is thought to date back to the Byzantine period and typically presents as cutaneous and subcutaneous tissue swelling, thickening, or painless nodule involving feet 80% of the time [6].

Mycetoma global distribution map
Mycetoma global distribution map, GIDEON. Dark blue color indicates recent reports of autochthonous cases.

 

Although bacterial mycetoma is endemic throughout the tropical world, S. somaliensis and S. sudanensis are only found in Eastern Africa, as names indicate. In other parts of the world, S.albus has been known to occasionally rear its head [7] in skin infections, although such occurrences are very rare. 

And here’s the most fascinating fact – a distant ‘cousin’ of these pathogens, Streptomyces cattleya is an effective carbapenem used to treat Streptomyces spp. infections. A family feud in all its glory!

 

Why are bacteria named as fungi?

Streptomyces are about 450 million years old. Despite being a genus of bacteria, they are misleadingly suffixed with ‘-myces’, which stands for ‘fungi’ in Greek. This is because the first known example of the species contained branching filaments [8], a characteristic common to fungi.

Other actinobacteria, such as Mycobacteria and Actinomyces bear similar morphological features and thus carry a badge of mushroom in their names. Mycoplasmata – elusive gram-unidentifiable bacteria called ‘fungus form’, were named so by A. B. Frank in 1889. He thought ‘the “infection threads” of the organism were hyphae, and he knew of no hyphal-forming bacteria’ [9].

 

Want to learn more about Streptomyces? Try GIDEON ebook Guide to Medically Important Bacteria, 20% off on our website.

Interested in Mycetoma? Take a look at Mycetoma: Global Status

 

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References:

[1] H. Campbell, “Geosmin: Why We Like The Smell Of Air After A Storm”, American Council on Science and Health, 2018. [Online]. Available: https://www.acsh.org/news/2018/07/28/geosmin-why-we-smell-air-after-storm-13240. [Accessed: 11- Sep- 2020].

[2] I. BEAR and R. THOMAS, “Nature of Argillaceous Odour”, Nature, vol. 201, no. 4923, pp. 993-995, 1964. Available: 10.1038/201993a0 [Accessed 11 September 2020].

[3] K. Chater, “Streptomyces”, Brenner’s Encyclopedia of Genetics, pp. 565-567, 2013. Available: 10.1016/b978-0-12-374984-0.01483-2 [Accessed 11 September 2020].

[4] A. Hasani, A. Kariminik and K. Issazadeh, “Streptomycetes: Characteristics and Their Antimicrobial Activities”, International Journal of Advanced Biological and Biomedical Research, vol. 2, no. 1, pp. 63-75, 2014. Available: http://www.ijabbr.com/article_7033_7733c8235876d7ba635f6c831a916648.pdf. [Accessed 11 September 2020].

[5] “Streptomycin”, App.gideononline.com, 2020. [Online]. Available: https://app.gideononline.com/explore/drugs/20910. [Accessed: 11- Sep- 2020].

[6] V. Lichon and A. Khachemoune, “Mycetoma”, American Journal of Clinical Dermatology, vol. 7, no. 5, pp. 315-321, 2006. Available: 10.2165/00128071-200607050-00005 [Accessed 11 September 2020].

[7] M. Martin, A. Manteca, M. Castillo, F. Vazquez and F. Mendez, “Streptomyces albus Isolated from a Human Actinomycetoma and Characterized by Molecular Techniques”, Journal of Clinical Microbiology, vol. 42, no. 12, pp. 5957-5960, 2004. Available: 10.1128/jcm.42.12.5957-5960.2004 [Accessed 11 September 2020].

[8] K. Chater, “Streptomycesinside-out: a new perspective on the bacteria that provide us with antibiotics”, Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 361, no. 1469, pp. 761-768, 2006. Available: 10.1098/rstb.2005.1758 [Accessed 12 September 2020].

[9] C. Krass and M. Gardner, “Etymology of the term Mycoplasma”, INTERNATIONAL JOURNAL of SYSTEMATIC BACTERIOLOGY, vol. 23, no. 1, pp. 62-64, 1973. Available: https://www.microbiologyresearch.org/docserver/fulltext/ijsem/23/1/ijs-23-1-62.pdf. [Accessed 12 September 2020].

Varicella vs. Monkeypox

Outbreaks of varicella and monkeypox in Africa are occasionally mistaken for “smallpox”   The following table was generated by an interactive tool in Gideon (www.GideonOnline.com) which allows users to generate custom charts that contrast clinical features, drug spectra or microbial phenotypes.

 

 

 

Outbreaks of Non-tubercuous Mycobacterial Infection in the United States

The following chronology of nosocomial mycobacteriosis outbreaks in the United States is abstracted from Gideon www.GideonOnline.com and the Gideon e-book series. [1,2] Primary references available on request.

1987 – An outbreak (17 cases) of Mycobacterium chelonae otitis media was caused by contaminated water used by an ENT practice in Louisiana.
1988 – An outbreak (8 cases) of foot infections due to Mycobacterium chelonae subspecies abscessus infections were associated with a jet injector used in a podiatric office.
1989 to 1990 – An outbreak (16 cases) of sputum colonization by Mycobacterium fortuitum was reported among patients on an alcoholism rehabilitation ward in Washington, D.C.
1991 (publication year) – An outbreak (6 cases) of Mycobacterium fortuitum infection in Washington was associated with contaminated electromyography needles.
1995 to 1996 – An outbreak (87 cases) of postinjection abscesses due to Mycobacterium abscessus in several states was ascribed to an adrenal cortex extract.
1998 – An outbreak (6 cases) of Mycobacterium mucogenicum bacteremia among bone marrow transplant and oncology patients in Minnesota was related to contaminated water.
1999 – An outbreak (10 cases) of intra- and periarticular Mycobacterium abscessus infection in Texas was caused by contaminated benzalkonium chloride used for injection.
2000 to 2001 – An outbreak (110 cases) of skin infections due to Mycobacterium fortuitum was caused by contaminated footbaths in California nail salons.
2001 – An outbreak of Mycobacterium chelonae keratitis in California was associated with laser in situ keratomileusis (LASIK).
2001 to 2002 – An outbreak of Mycobacterium simiae in a Texas hospital was related to contaminated tap water.
2002 – An outbreak (14 confirmed and 11 suspected cases) of soft tissue infections due to Mycobacterium abscessus followed injections of cosmetic substances administered by unlicensed practitioners in New York City.
2002 – An outbreak (115 cases or more) of cutaneous infection by Mycobacterium fortuitum was associated with a contaminated footbath in a nail salon in California.
2002 (publication year) – An outbreak (34 cases) of Mycobacterium chelonae soft tissue infection in California was associated with liposuction.
2002 to 2003 – An outbreak (4 cases) of Mycobacterium chelonae infection among patients undergoing rhytidectomies in New Jersey was caused by a contaminated methylene blue solution.
2003 – An outbreak (3 cases) of Mycobacterium goodii infection was associated with surgical implants in a Colorado hospital.
2004 – An outbreak (12 cases) among Americans of soft tissue infections caused by Mycobacterium abscessus following cosmetic surgery performed at various clinics in the Dominican Republic.
2004 – An outbreak (143 cases) of mycobacterial skin and soft tissue infection (presumed M. fortuitum) was reported among persons attending nail salons in California.
2008 – An outbreak (4 cases) of Mycobacterium mucogenicum bloodstream infections was reported among patients with sickle cell disease, in North Carolina.
2009 (publication year) – An outbreak (6 cases) of Mycobacterium chelonae infection was associated with a tattoo establishment.
2009 – An outbreak (2 cases, 1 confirmed) of Mycobacterium haemophilum skin infection was associated with a tattoo parlor in Washington State.
2011 (publication year) – An outbreak (3 cases) of Mycobacterium bolletii/M. massiliense furunculosis was associated with a nail salon in North Carolina.
2011 (publication year) – An outbreak of Mycobacterium abscessus infection was associated with outpatient rhytidectomies.
2011 – An outbreak (2 cases) of Mycobacterium haemophilum infection was reported among persons receiving tattoos in the Seattle, Washington region. {m 201108122444}
2011 (publication year) – An outbreak (11 cases) of Mycobacterium porcinum infection in a Texas hospital was related to contamination of drinking water.
2011 to 2012 – An outbreak (19 cases) of Mycobacterium chelonae infection involving multiple states was associated with contaminated ink used in tattoo parlors.
2011 to 2012 – An outbreak (15 cases) of infection by rapidly-growing mycobacteria was reported among pediatric hematopoietic cell transplant in a Minnesota hospital.
2013 – An outbreak (2 cases) of non-tuberculous mycobacterial infection was associated with fractionated CO2 laser resurfacing procedures performed at a clinic in North Carolina.
2013 to 2014 – An outbreak (19 cases) wound infection was reported among Americans who had traveled to the Dominican Republic for cosmetic surgery – including 12 due to Mycobacterium abscessus and 2 Mycobacterium fortuitum
2014 – An outbreak (15 cases, 4 fatal) of Mycobacterium abscessus infection in a South Carolina hospital was associated with contact of equipment with contaminated tap water.

References:
1. Berger SA. Infectious Diseases of the United States, 2014. 1145 pages, 478 graphs, 12,294 references. Gideon e-books, https://www.gideononline.com/ebooks/country/infectious-diseases-of-the-united-states/
2. Berger SA. Non-Tuberculous Mycobacteria: Global Status, 2014. 61 pages, 31 graphs, 584 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/non-tuberculous-mycobacteria-global-status/

Note featured on ProMED

2014 series of GIDEON eBooks

The 2014 GIDEON ebook series has been released.

This edition incorporates all content added since publication of the last series. Country-series eBooks now include the vaccination schedules for every reporting country as an extra chapter.
Additionally, four new volumes have been added to the series.

Titles now include:

Country series (231 volumes)
Disease series (188 volumes)
GIDEON Guide to Antimicrobial Agents
GIDEON Guide to Vaccines
GIDEON Guide to Medically Important Bacteria
GIDEON Guide to Medically Important Yeasts

The four newer titles incorporate content from GIDEON’s Drugs, Vaccines, Bacteria, Mycobacteria and Yeasts modules. These and all other eBooks in the series are updated annually

These ebooks are available on the GIDEON eBooks website as well as through distributors such as EBSCO and Ingram.

Microbiology References and Vaccination schedules

Over the past couple of months, we have rolled out a number of product updates to the GIDEON web app.

Microbiology References
References have been added to the improved notes and ecology sections for most organisms in the Microbiology sub-modules of Bacteria, Mycobacteria and Yeasts.

Vaccine Schedules
Vaccine schedules for each country have typically appeared in a number of notes in the Diseases module. These vaccine schedules have now been added to the Travel section, so it’s very easy to scroll through countries and compare their vaccination schedules.

For example see the initial travel note for Australia:
Australia vaccination schedule

With easy access to the vaccine abbreviations:

Vaccine abbreviations

Free-living Amoebae in Southeast Asia

To date, infection by free-living amoebae has not been described in Myanmar, Laos or Cambodia. Thailand reported its first case of primary amoebic meningoencephalitis in 1983, and by 1987 an additional five cases had been reported. 22 cases were reported to 2004: 10 due to Naegleria fowleri, 11 Acanthamoeba, and 1 Balamuthia mandrillaris. A study performed during 2001 to 2004 found that amoebae accounted for 2% of ulcerative keratitis cases in Bangkok; and as of 2005, Acanthamoeba, Naegleria, Hartmanella, Vahlkampfia and Vannella had been identified in soil and water samples from 14 provinces. [1,2]

References:
1. Berger SA. Infectious Diseases of Thailand, 2012. 496 pages, 164 graphs, 2316 references. Gideon e-books, https://www.gideononline.com/ebooks/country/infectious-diseases-of-thailand/
2. Berger SA. Free-living Amoeba: Global Status, 2012. 24 pages, 1 graph, 368 references. Gideon e-books, https://www.gideononline.com/ebooks/disease/free-living-amoeba-global-status/

Note featured on ProMED

Pathogens Associated with Animal Bites

Gideon www.GideonOnline.com lists 31 species of bacteria which have been associated with human infection following the bites of animals:
– Bacteroides tectus
– Bergeyella zoohelcum
– Bisgaard’s taxon
– Capnocytophaga canimorsus
– Corynebacterium canis
– Capnocytophaga cynodegmi
– Corynebacterium freiburgense
– Corynebacterium kutscheri
– CDC NO-1
– Erysipelothrix rhusiopathiae
– Fusobacterium canifelinum
– Halomonas venusta
– Kingella potus
– Moraxella canis
– Mycobacterium vulneris
– Neisseria animaloris
– Neisseria canis
– Neisseria weaveri
– Neisseria zoodegmatis
– Pasteurella caballi
– Pasteurella canis
– Pasteurella dagmatis
– Pasteurella multocida
– Pasteurella stomatis
– Psychrobacter immobilis
– Spirillum minus
– Staphylococcus intermedius
– Streptobacillus moniliformis
– Vibrio charchariae
– Vibrio harveyi

Although virtually all literature on the subject advocates administration of tetanus prophylaxis following animal bites, few if any cases of bite-associated tetanus have been documented.

Updated Microbiology module

GIDEON’s redesigned Microbiology module has been launched (screenshot). Following the update of the GIDEON Diagnosis module, we’ve implemented many of the new features in Microbiology, including

  • New tabs
  • Suggestions
  • Dynamic identification
  • Usability improvements

New tabs

The new tabs in Microbiology replace the older radio buttons and make it easier to reach each function. For each category: Bacteria, Mycobacteria and Yeasts there is easy access to Identify or Lists.

Suggestions

GIDEON’s Microbiology Compare function, until now, has ranked phenotypic tests which are most likely to impact the Identification list. Now, the top four tests which are most likely to focus and shorten the list of possible organisms are displayed and dynamically updated as each new test result is entered. Clickable boxes which allow the user to enter a “yes”, “no” or “unknown”, appear and enlarge each time the mouse passes near a test.

Dynamic identification

The Identify button has been eliminated! Now, the Identification list is automatically updated as test results are entered. This feature demonstrates the effects of each new test result as it is entered.

Diagnosis results buttonsThe familiar buttons: Compare, Why Not, Open case, Save case, Remove All, Print, Email are all in the Identification list area.

Usability improvements

Updated lists

The organism lists have been updated to extend the length of the screen. The organisms can be selected by clicking the check boxes to their left and then Compared. Clicking on expands the list of synonyms.

Collapsible windows

Windows in Identify, such as Suggestions and Phenotypic Tests can be minimized and hidden. For example to not see suggestions, click on the minimize button Minimize button to the left title.

Mouse overs
More mouse-overs have been added: Clickable boxes expand as you mouse over them, and display clear symbols to select “yes” or “no.”

Phenotype
You can now click on the tests  in the Phenotype window.

Quick sorting
Probability sort arrowIdentification results can be sorted alphabetically or by probability easily by clicking the column title.

Window resizing
Changing vertical window size expands size of Phenotypic tests and Identification list sub-windows in Identify and Organism list. This is a great feature for larger monitors.

Previous version
Click “Original Microbiology” to use the older interface.

Update: See video demonstration

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