Antibiotics and Proteins Made by Bacteria

(Chapter 12)


http://photoscience.la.asu.edu/photosyn/courses/BIO_343/lecture/antibio.html

Antibiotics

The rapidly increasing resistance of selected microbes against a large number of antibiotics has become a very serious issue worldwide (a World Health Organization fact sheet on this issue can be found at http://www.who.int/inf-fs/en/fact194.html). The Center for Disease Control (CDC) has informative web sites on this topic (http://www.cdc.gov/drugresistance and http://www.cdc.gov/antibioticresistance). An alarming number of microorganisms that occur in hospitals have become resistant against virtually all antibiotics. Several strains of pathogenic bacteria have been discovered that are resistant to all known antibiotics. Resistance against so many different antibiotics has been induced by the indiscriminate use of heavy doses of antibiotics in health care. Strains that have developed resistance survive and can propagate productively as all competitors have been killed off. The discovery of bacterial strains with so many resistances has put development of new antibiotics into high gear. One needs to have effective back-up antibiotics before bacterial strains with resistance to all currently known antibiotics have developed. The search for new antibiotics in many cases involves the combination of brute-force screening and targeted genetic modification of microorganisms that produce antibiotics: by selected modifications antibiotics with slightly different structure and properties may be produced by these microbes. Nonetheless, the search for new antibiotics probably will need to be a continuing one: A new type of antibiotic (Zyvox) was introduced in 2000, but the first Zyvox-resistant strains already were found a year later.

Many known antibiotics are produced by actinomycetes (particularly by representatives of the genus Streptomyces), which are filamentous soil bacteria. The antibiotics are produced via secondary metabolic pathways, and originate from a small number of simple precursors, including amino acids, small fatty acids, sugars, and nucleic acids. Secondary metabolism is more specialized than primary metabolism and varies widely even among members of the same genera. Several new antibiotics have been found by targeted or random inactivation of particular genes, leading to utilization of alternate biochemical pathways. It is still pretty much a matter of just testing out which mutants may give rise to novel and active antibiotics, but progress is being made towards this semi-rational design of such antibiotics. However, it will be some time before such antibiotics will be used as first a lengthy testing and certification procedure will need to be followed for each compound.

Milk production

By means of expression of foreign genes, essentially any protein from any source can be produced by bacteria. Barring the need for glycosylation or other post-translational processes to yield an active enzyme, large amounts of eukaryotic (plant, human, or animal) protein can be made by bacteria as long as they have been provided by the right gene construct. This can have a wide variety of implications, some of which are controversial. For example, a growth hormone of cows, bovine somatotropin (BST; sold under the trade name Posilac), has been produced in large quantities by genetically engineered micro-organisms. When given to the cows in small amounts, milk production in dairy cows increases by 10-25%. This increase in milk production per cow follows recent milk production increases obtained by traditional breeding: since 1950, milk production per cow has more than doubled. However, as BST leads to increased milk production, it will drive prices lower, which may force small farmers out of business. However, the process of increasing monopolization by bigger companies is nothing new, and the BST-induced increase in production is peanuts compared to breeding-induced increases over the last 40 years. The FDA (Food and Drug Administration) has found the BST to be safe for human consumption. However, public is generally perceived to be wary of "BST cows" and several supermarket chains claim to not sell any milk from BST-treated cows. The outcry from some consumer and small-farmer-interest groups has caused the FDA to perform additional trials, which backed up the initial findings. In some respects the outcry regarding the use of genetically engineered hormones in lifestock is irrational, in that lifestock has been fed antibiotics and hormones for years (to reduce infections and to increase production) without a lot of opposition from the consumer. Even though the general discussion and perception of the BST issue in most cases does not have a rational foundation, it forces people to start thinking about the effects of biotechnology in their everyday lives. Also, the issue provides a challenge to well-informed individuals to lead a public discussion to critically evaluate how appropriate, ethical, and healthy current lifestock management procedures really are. BST-related documents from different perspectives can be found at http://www.nalusda.gov/bic/BST/BST.html, and http://www.nalusda.gov/bic/BST/other.html.


http://photoscience.la.asu.edu/photosyn/courses/BIO_343/
This web site contains the syllabus for the MBB 343/BIO 343 course, describes the laboratory experiments, and covers materials that will be discussed in the lecture but that have not been covered sufficiently in the required textbook (B.R. Glick and J.J. Pasternak (1998) Molecular Biotechnology: Principles and Applications of Recombinant DNA, second edition).

Most of the material at this website has been compiled over the years by Wim Vermaas, a Professor in the Plant Biology Department. Instructors this year are Wim Vermaas (weeks 5-8, 12-13, and 15-16) and David Rhoads (weeks 1-4, 9-11, and 14).

Contact information: Wim Vermaas: office location: LS-E549; phone: (480) 965-3698; Email: wim@asu.edu; office hours for Fall 2002: M and TH 10:40-11:30.
David Rhoads: office location:LS-E511; phone (480) 965-2583; Email: david.rhoads@asu.edu; office hours for Fall 2002: T/TH 1:30-2:30 pm on the days that he lectures only.

Material at this site may be used freely by others as long as the source of the information is acknowledged. Contact the appropriate web master to learn about the rules of using materials contained at other web sites that are referred to at this site.