Why Some Bacteria Are Becoming Antibiotic Resistant

Almost 60 years ago the first antibiotics were developed, and they were created at a time when previously untreatable infections such as tuberculosis, gonorrhea, and syphilis could be almost miraculously cured. Infections like these could be a death sentence, and until recently they many be just that again. Microbes are learning the ability to fight of these antibiotics and become resistant to them. They are gaining resistance through a number of different ways, and science is in a race to keep up with there amazing evolution.

Bacteria are the common name for prokaryotic cells, which lack a nucleus. Rather they have a nucleoid region where their DNA is stored in direct contact with their cytoplasm. Their DNA, through transcription and translation, directs ribosomes to assemble proteins. They reproduce by binary fission, and are mostly heterotrophic. Bacteria can exchange DNA in three ways: transformation, transduction, and conjugation. In transformation a bacterial cell becomes competent, or able to take up DNA from the surrounding fluids. In conjugation two bacterial cells, a donor and a recipient join and DNA is transferred from one to the other. In these cases the new DNA either incorporates itself into the existing DNA or forms an independent molecule within the cell called a plasmid (Christensen).

Antibiotics are substances produced by microorganisms that kill or inhibit other microorganisms from growing or reproducing. Antibiotics are products of the earth and are all-natural.

For clinical purposes, bacteria are said to be resistant to an antimicrobial when they are insignificantly affected by concentrations of the drug that can be achieved at the site of the infection. As might be expected, achievable concentrations vary dramatically from place to place in the body. Sensitivity of organisms to antimicrobials may be quantified by the minimum concentration required to inhibit their growth (minimum inhibitory concentration, MIC) or by the minimum concentration required to kill them within a specified period of time (minimum bactericidal concentration, MBC). Because they are easier to measure and apply to both bactericidal and bacteriostatic drugs, MICs are more frequently used. Tables of typical MICs for many bacterial species/antimicrobial pairs are widely available. When combined with knowledge of the time course of antimicrobial concentrations at various sites in the body, these MICs can be used to guide rational selection antimicrobials for particular infections. Application of this rational approach to selection is still developing and unexpected results do occur.

Microbial resistance to antibiotics can be inherent or natural resistance. Bacteria may be inherently resistant to an antibiotic. Other microbes developed acquired resistance. This is when bacteria can develop resistance to antibiotics. So bacterial population's previously sensitive to antibiotics become resistant. This type of resistance results from changes in the bacterial genome (Stapleton). Two genetic processes in bacteria drive acquired resistance: mutation and selection (or vertical evolution), or exchange of genes between strains and species (or horizontal evolution) (Garrett 420).

Vertical evolution is essentiality Darwinian evolution, which is driven by natural selection. So a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population. In the presence of the antibiotics then, the wild type (non-mutated) are killed and the resistant mutant is allowed to grow and flourish (Garrett 421). The mutation rate for most bacterial genes is approximately 10-8. This means that if a bacterial population doubles from 108 cells to 2 x 108 cells, and there is likely to be a mutant present for any given gene. Since bacteria grow to reach population densities far in excess of 109 cells, such a mutant could develop from a single generation during 15 minutes of growth resistance to other strains and species during genetic exchange processes (Levy).

The combined effects of fast growth rates, high concentrations of cells, genetic processes of mutation and selection, and the ability to exchange genes, account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial adaptation, or resistance, to the antibiotic environment seems to take place very rapidly in evolutionary time (Stapleton).

Fleming first discovered penicillin, the first and most famous antibiotic, in 1929 when he found that a Penicillium mold inhibited the growth of bacteria in a petri dish. However, he failed to recognize the therapeutic potential of this and it remained for Florey, an Englishman, to first use Penicillin for therapy in 1940. It was, and is, one of the most active and safe antibacterials available. Because of their effectiveness and large therapeutic index, penicillin and many closely related derivatives, collectively known as the Penicillins, and the closely related Cephalosporines (discovered in the 1960s) are among the most important families of antibacterials available today.

Penicillium and Streptomyces are major sources of antibiotics used therapeutically. Bacillus are the most notable bacterial group from which useful antibiotics have been derived. Synthetic antimicrobials, e.g., the sulfonamides, have always constituted an important source of antimicrobials. Semisynthetic antimicrobials are those derived from chemical modifications of naturally occurring antibiotics. This constitutes an ever more important group of antimicrobials as new drugs, with special properties, are developed.

The fundamental and most frequent grouping of antimicrobials is based on their chemical structure. Each of the following groups has a structural component that defines the group. Addition or subtraction of chemical groups from the core structure leads to the various members of the group. Some key groups are:

1. Beta-lactam antibiotics

a. Penicillins: derivatives of 6-aminopenicillanic acid. e.g., penicillin G

b. Cephalosporins: derivatives of 7-aminocephalosporanic acid, e.g., cephalexin

2. Macrolides: have a large ring structure. Sometimes referred to as the "erythromycins." e.g.,

3. Lincosamides: name derived from the first member found, e.g., lincomycin

4. Aminoglycosides: composed of aminosugars linked by glycosidic bonds to various bases. e.g., gentamicin

5. Tetracyclines: have a rigid structure composed of 4 fused benzene-like rings. e.g., tetracycline.

6. Polypeptides: as the name says, aminoacids linked by peptide bonds form