Mycobacterium tuberculosis

This article presents a technique for bringing the history of microbiology to life in an exciting way. Eight miniature models were created, based on photographs or drawings, showing scientists at work in their labs. The models chosen represent important discoveries in microbiology, illustrating changes and advances in techniques and tools over the history of the discipline from 1600 through 2000. They serve as a novel and engaging teaching tool. While the instructor still presents the historic facts, the use of models provides the feeling of being there! They can also serve as a record for the future.

Malaria is a disease caused by parasites of the genus Plasmodium, transmitted through the bites of female anopheles flies. Plasmodium falciparum causes severe malaria with undulating high fever (malaria tropica). Literary evidence of malarial infection dates back to the early Greek period, when Hippocrates described the typical undulating fever highly suggestive of plasmodial infection. Recent immunological and molecular analyses describe the unambiguous identification of malarial infections in several ancient Egyptian mummies and a few isolated cases in Roman and Renaissance Europe. Although the numbers of cases are low, there is evidence that the overall infection rates may have been relatively high and that this infectious disease may have had a significant impact on historical populations.

Cholera is an acute disease of the gastrointestinal tract caused by Vibrio cholerae. Cholera was localized in Asia until 1817, when a first pandemic spread from India to several other regions of the world. After this appearance, six additional major pandemics occurred during the 19th and 20th centuries, the latest of which originated in Indonesia in the 1960s and is still ongoing. In 1854, a cholera outbreak in Soho, London, was investigated by the English physician John Snow (1813 to 1858). He described the time course of the outbreak, managed to understand its routes of transmission, and suggested effective measures to stop its spread, giving rise to modern infectious disease epidemiology. The germ responsible for cholera was discovered twice: first by the Italian physician Filippo Pacini during an outbreak in Florence, Italy, in 1854, and then independently by Robert Koch in India in 1883, thus favoring the germ theory over the miasma theory of disease. Unlike many other infectious diseases, such as plague, smallpox, and poliomyelitis, cholera persists as a huge public health problem worldwide, even though there are effective methods for its prevention and treatment. The main reasons for its persistence are socioeconomic rather than purely biological; cholera flourishes where there are unsatisfactory hygienic conditions and where a breakdown of already fragile sanitation and health infrastructure occurs because of natural disasters or humanitarian crises.

Mycobacterium tuberculosis (Mtb) is notoriously difficult to eradicate even with combinations of antibiotics, leading researchers to pursue alternate strategies, including one aimed at bolstering host defenses against this pathogen. “Our inability to effectively treat all infected individuals necessitates a deeper understanding of the host-pathogen interface to facilitate new approaches,” says Amy Barczak of the Ragon Institute and Massachusestts General Hospital in Boston, Mass. She was one of several experts who participated in the symposium “Aiming at Non-Conventional Approaches to TB Therapies,” held at the 2016 ASM Microbe Conference in Boston last June.

I recently had the pleasure of reading this wonderful book. Metabolism and Bacterial Pathogenesis came at the right time, because I work on a human-exclusive pathogen for which some strains collected from patients are auxotrophic, making me wonder: how is it that a pathogen that is very effective at surviving in humans requires one of the very amino acids that is limiting in humans? Every chapter in this book, directly or indirectly, suggested to me that the answer I am looking for it may be very near, and what I have to do is to dig through some of the numerous references listed. These references are so limited that it made me recall the frequent editorial restrictions on references—clearly, the contributors were encouraged to freely discuss the details in depth. The contributors also suggest provocative and challenging new concepts, e.g. “pathometabolism.” This term encompasses the complex metabolic interactions between host and bacterial pathogen, concepts that could lead to novel antimicrobial therapeutics.

The highly conserved Nus factors of bacteria were discovered as essential host proteins for the growth of temperate phage λ in Escherichia coli. Later, their essentiality and functions in transcription, translation, and, more recently, in DNA repair have been elucidated. Close involvement of these factors in various gene networks and circuits is also emerging from recent genomic studies. We have described a detailed overview of their biochemistry, structures, and various cellular functions, as well as their interactions with other macromolecules. Towards the end, we have envisaged different uncharted areas of studies with these factors, including their participation in pathogenicity.

The anthropocentric focus of microbiology has painted a negative image of the largely unknown bacterial community, when in reality bacteria play many more significant roles than influencing human health. It is important to convey this message to college students so that they can make informed decisions as an educated citizen. Non-major students taking a microbiology course however, may demonstrate poor interest and become further alienated by the abstract terminologies. Recent studies suggest that story writing may enhance scientific literacy, and role-play activities are effective means to engage students. Here, I combine these two strategies and introduce a writing activity in which students impersonate an assigned bacterium. Through this writing exercise, students demonstrated deeper understanding of key concepts in microbiology, greater appreciation of the broad roles of bacteria, and improved attitude towards science and science learning.

Mycobacteria are slim bacteria with unusual growth requirements and unique structural and biochemical properties that place them in their own category of microorganisms. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the best-known mycobacterial infection of humans. Buruli ulcer and leprosy are two highly disfiguring and stigmatizing neglected tropical diseases (NTDs) that occur almost exclusively among the impoverished living in developing countries. Buruli ulcer is a highly disfiguring skin infection caused by M. ulcerans. Buruli typically strikes school-age children and manifests as a large ulcer usually appearing on the limbs. The ulcer of Buruli disease has a number of catastrophic consequences for the patient, including a profound socioeconomic impact and the widespread belief that witchcraft and curses play an important role in transmitting the disease. The most effective treatment of large ulcers requires access not only to antibiotics but also to different surgical modalities, including skin grafting. Leprosy (also known as Hansen’s disease) is caused by M. leprae. Leprosy proceeds along either one of two clinical courses. The majority of patients develop the so-called tuberculoid form. Such patients have the ability to mount strong immunological responses against M. leprae and, as a result, develop only localized disease. Far more severe is the lepromatous form of leprosy. These patients experience widely disseminated disease in the skin and nerves and even the eyes, nose, mouth, and bones. The most widely used multidrug therapy (MDT) drug regimen calls for dapsone to be administered together with the antibacterial drugs rifampin and clofazimine.

The Journal Watch section highlights published journal articles which discuss recent developments and new technology used in microbiology and related fields.

Nucleic acid sequencing of various bacterial genes and other DNA targets has been used for determining the phylogeny of bacteria and for their identification. A brief overview of nucleic acid sequencing is shown in this chapter. DNA targets have conserved regions flanking variable regions that can be used to differentiate closely related bacterial species. The routine use of sequencing can greatly enhance the ability of the clinical microbiology laboratory to identify bacteria on many levels. Of consideration in the routine use of DNA target sequencing is the need for technical expertise and its cost. The chapter addresses preparation of DNA from pure culture. Certain conventional methods such as latex agglutination assays are quicker, simpler, and less expensive than DNA target sequencing for the identification of beta-hemolytic streptococci. Basic conventional methods perform well in identifying common isolates, such as Bacteroides fragilis group, Peptostreptococcus spp., and most Clostridium spp. DNA target sequencing can provide more accurate identifications, especially since databases from conventional methods often are not current and do not reflect the tremendous genetic diversity within anaerobic taxa. For agents of bioterrorism, i.e., Bacillus anthracis, Brucella spp., Clostridium botulinum, Francisella tularensis, and Yersinia pestis, 16S rRNA sequencing has varying utility. Molecular studies have enhanced our knowledge about the taxonomical diversity among bacteria and allowed better definition of the epidemiology of bacterial infections.