The World of O
Biology Papers Suck!

Here is a wonderful example of why I hate doing Biology papers!

Hey WOW look a paper done by me! Not too bad...

Introduction:
The treatment of infectious diseases is in constant equilibrium with the development of antibiotic resistant strains of pathogens. Upwards of a dozen biochemical mechanisms have been discovered to date; these are encoded by hundreds of different genes. The bacterial population has essentially stockpiled a considerable armament of genetic defenses against antibiotics. Antibiotic resistant genes can be disseminated among bacterial populations by several processes, but principally by conjugation. These genes are carried by plasmids, transpons, and other elements capable of inter-generic and inter-specific mobility (Davies J. 1990). Horizontal gene transfer has played a primary role in this development and dissemination of antibiotic resistant genes. Thus the overall problem of antibiotic resistance is one of genetic ecology. Of course the study of the evolution of antibiotic resistance cannot be talked about without considering both the mechanisms of resistance as well as the selective environment. In all cases studied there is a direct correlation over time between antibiotic use and the increase in proportion of resistant to non-resistant strains. Clearly selective pressures exerted by man have played a role in the evolution of new antibiotic resistant strains of microbes.
Bacteria can acquire target-mediated antibiotic resistance in three main ways. The first and most obvious is mutations in the chromosomal genes encoding the target. This mechanism of antibiotic resistance has been the hardest to observe in the laboratory presumably because several mutational events are required in order to produce an allele which encoding a resistant protein. This mechanism is much more important in combinations with other mechanisms. The second of which is the recruitment of genes, which encode for the antibiotic resistant, target molecule. This mechanism is characteristic of one event such as the acquisition of a plasmid for example leads to a fully antibiotic resistant strain. The third and last mechanism is intrageneic recombination of the chromosomal gene encoding the sensitive target molecule with related genes, resulting in novel alleles that are called mosaic genes which encode resistant proteins (Lorenz MG, Wackernagel W. 1994).

Selective pressures:
Selective pressure is a general concept that refers to the many factors that create an environmental landscape and allow organisms with novel mutations or newly acquired characteristics to survive and proliferate. The global release of antibiotics over the past fifty years has done more than apply pressure for the selection of protective mechanisms in the microbial population; the horizontal gene transfer of unrelated genes to resistance must have taken place simultaneously. This inadvertently has given many microbes a veritable arsenal of genetic information, which is readily accessible to others. Thus further increasing potential resistance to future antibiotics.
The major driving force of this selective pressure is the phenomenon described as antibiotic concentration dependent selection. The hypothesis is that low-level resistant variants are exposed to an environment in which the antibiotic concentration levels are selective for that variant. The concentrations with-in this environment may change over time leading to a potential for further evolution towards higher resistance levels, through the natural occurrence of new genetic variation (Spratt BG. 1994).
Random genetic drift is also a driving force of evolution under extreme circumstances. During times of mass extinction, such as the use of active antibiotics, a single organism or small group of organisms may have survived where neighboring organisms have been eliminated. This situation can occur even though both the surviving and neighboring organisms may have had low levels of resistance. This leads to the possible extinction of one mechanism of resistance while the other mechanism resistance is selected for.
Upon looking at the bigger picture we can see that a wide variety of antibiotic resistant bacteria are themselves spread out over a number of different ecological niches. The spread of these organisms is an issue, which is independent of horizontal gene transfer of resistant genes. These strains are subject to many different environments and the following are important factors which contribute to the macro-ecology of such strains: 1) health care institutes and the maintenance and transmission of resistant strains with-in the community; 2) The proliferation of antibiotic resistant strains in animals and their different environments; 3) global transfer of resistant strains due to human travel and the food business, including the trafficking of live animals and associated products.

Mutations:
One must not over-estimate the role of spontaneous mutations in the evolution of antibiotic resistances. Although mutations are a mechanism for evolving antibiotic resistances they are more an exception rather then the rule. Since it has been shown that resistance arises from successive mutational steps, for a strain resistant to four drugs the frequency of appearance would be greater than 1 in 1025 (M.Teuber, 1999). While the frequency of finding these point mutations in the laboratory are relatively low, in clinical practice, resistant strains do appear during the course of patient treatment.
Two other roles of mutation can be identified in the evolution of antibiotic resistance determinants. First it is likely that hypermutable strains and mutor genes have a significant influence in the process of horizontal gene transfer. Extensive tailoring and adapting of the resistant genes takes place during the passage from source organism to recipient organism. Recent studies have shown that many natural bacterial isolates, particularly pathogenic strains, may be hyper-mutagenic because they carry one or more mutor genes: in some cases the mutor genes involved, such as mutT, would favor the conversion of high G + C sequences and thus readily contribute to adaption of the codon usage patterns to new cellular environments. Second the development of extended spectrum b-lactamase (which engenders resistance to newer synthetic derivatives of penicillins and cephalosporins) occurs by protein engineering in vivo. Point mutations that change the critical amino acids in b-lactamase have been characterized; these lead to alterations in substrate/enzyme recognition and have generated a huge family of genetically engineered resistance genes (Neu HC, 1992).

Acquisition:
A-sexual organisms such as bacteria transfer DNA by three parasexual processes: conjugation, transduction (phage mediated), and transformation. Conjugation and transduction transfer particular parts of the chromosome into integration sites of episomal elements, where as transformation is a generalized process where any part of the chromosome may be transferred. The significance of this is the formation of tandem assemblages of resistant genes with-in a single mobile genetic element to form multi-drug resistant clusters. The problem is that the genes of virulence are usually included in the cluster, which contains the resistant genes. The most common manor in which these clusters are integrated is gene capture through integrons. These structures reveal a significant relationship between resistance and virulence genes and imply that the selective pressure of antibiotic use could have promoted the spread of pathogenicity determinants in the development of new pathogens. In addition to its role in resistance and pathogenicity, integron-driven gene capture is also likely to be important in the more important process of horizontal gene transfer in the evolution of the bacterial genome.
Transformation leads to another scenario in which bacteria are left with a mosaic of genes acquired from the host and other bacteria, often members of a different species. These bacteria show variants of the antibiotic target, which are metabolically active but show a lower affinity for the antibiotic. These polymorphisms are identical to the original allele in some parts of the gene but also contain polymorphisms derived from the introduced gene in other parts. There is evidence to support the idea that mosaic genes are continually generated in transformable organisms, probably in all genes. Of course most mosaic alleles will be lost in the diversity reduction events soon after they arise, much like all new variants, they are present in low concentrations at all times. However if a mosaic gene expresses a phenotype, which is favorable by selection, the organism carrying it will most likely be the founder of a new population, leading to an increase in the frequency in which this mosaic allele is found in the population. The large scale use of antibiotics has created a selection pressure that has promoted the spread of mosaic genes encoding proteins with decreased affinity for at least two important classes of antimicrobial agents: the b-lactamase and the sulfonamides (Hughes V.M. and Datta N 1983).
In several transformable bacteria, horizontal gene transfer has promoted the emergence and spread of antibiotic resistance by 1) the generation of similar target enzymes which have a lower affinity for the antibiotic, 2) the spread of these alleles among genetically diverse organisms, and 3) the accumulation of several genes conferring resistance to generate novel strains with high levels of antibiotic resistance or a broad spectrum of antibiotic resistances.

Conclusion:
The temptation to describe the emergence of resistances to antibiotics as a war in which we are loosing ground obscures the fact that the evolution and spread of antibiotic-resistant organisms are the artificial result of selection pressure imposed by man. The speed at which bacteria develop new and complex resistances reflects the enormous diversity of the gene pool of these organisms, the mobility of genes across genus and species boundaries, and the short generation times and large population sizes of the bacteria. Population studies employing molecular techniques have illustrated some of the mechanisms and probable paths in-which antibiotic resistance has evolved and have provided a glimpse of the genetic diversity of the bacteria.
Reducing the selective pressures the bacteria are exposed to by avoiding the use of broad-spectrum antibiotics, the agricultural use of antibiotics, and the indiscriminant medical use of antibiotics without adequate supervision is not a new idea, which might provide a mechanism with which to combat the rate at which antibiotic resistance arises and spreads. However this possible solution only deals with slowing the rise of antibiotic resistance rather than eliminating it once it has become apparent.

Basically we're all gonna die! SO you might as well go out and try and have sex with as many people as possible.

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Just for fun I added
this chest radiograph
of a lady. It seems
sort of Biology related.
One of these things in
the picture just doesn't
seem right... one of these
things is not like the
other... one of these things
just doesn't belong.....
can you pick it out?

I'll give ya a hint:
It's got Bristles.

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Please Click on Dr.Judy Above for an Informative Webpage Which I Frequent Quite Often...

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Did you actually read it? It's actually surprizingly informative about antibiotic resistant diseases... a very hot topic as of latly.