Bacteria 



Break the 



Antibiotic 



Bank 



Drug-resistant genes are leaping 

 across species boundaries 



by John Maynard Smith 



The brief era in which such infectious 

 diseases as pneumonia, tuberculosis, and 

 gonorrhea could be effectively controlled 

 by antibiotics may be nearing its end. 

 Strains of disease-causing bacteria resis- 

 tant to penicillin and other antibiotics have 

 rapidly evolved, and — even more unset- 

 tling — such resistance can often be passed 

 from one type of bacterium to another. 



Penicillin, for example, kills bacteria by 

 binding irreversibly to enzymes (called 

 penicillin binding proteins, or PBPs for 

 short) that normally help bacteria manu- 

 facture cell walls. The penicillin bond puts 

 the PBP enzymes out of action and thus 

 prevents bacteria from synthesizing new 

 cell walls. As a result, the bacteria die. 



But bacteria can evolve resistance to 

 penicillin in two ways. The first and most 

 common method is for bacteria to arm 

 themselves with B-lactamase, an enzyme 

 that breaks down penicillin before it can 

 do any damage. The gene that codes for 6- 

 lactamase is not actually part of the bacte- 

 rial chromosome; it is carried on an acces- 

 sory piece of DNA known as a plasmid. 

 Plasmids, which are self-replicating cir- 

 cles of DNA, can travel from one bac- 

 terium to another, and from one kind of 

 bacterium to another, across very wide 

 taxonomic boundaries. 



Almost all bacteria carry plasmids, 

 which confer a wide variety of properties 

 on their hosts, including the ability to me- 

 tabolize unusual nutrients, to resist heavy 

 metal ions and toxic substances, and to re- 

 sist attack by viruses. Plasmids that en- 

 code for 6-lactamase probably originated 

 a long time ago. Penicillin has been 

 around for many millions of years, al- 

 though its clinical use is new. It is manu- 

 factured by some soil fungi, presumably 

 because it helps them to compete with soil 



bacteria. Most likely, a plasmid that per- 

 mitted the production of 6-lactamase first 

 evolved in a soil bacterium, and it and its 

 host then proliferated because of the pro- 

 tection it conferred. 



During the last fifty years, as a result of 

 the widespread use of antibiotics, plas- 

 mids with the gene for B-lactamase have 

 been incoiporated in most of the bacteria 

 that live in humans. Acquiring plasmids 

 that carry the genes they need is one way 

 bacteria can evolve and become adapted to 

 changed circumstances — in this case the 

 increased exposure to penicillin. This is 

 similar to the process of symbiosis, 

 whereby higher organisms sometimes ac- 

 quire new abilities by linking up with a 

 partner — such as a bacterium, fungus, or 

 alga — that has the necessary genes. 



For example, the roots of peas and 

 beans have bacteria that provide them with 

 nitrogen in usable form, and heathers have 

 fungi associated with their roots that en- 

 able them to live on nutrient-poor, acidic 

 soils. Similar symbioses enable termites to 



digest wood and some animals to live in 

 deep-sea vents. The difference between 

 these examples and plasmids is that the 

 symbionts of higher animals and plants 

 were once capable of a free-living exis- 

 tence, and often still are, whereas plasmids 

 are mere circles of DNA that could never 

 have multiplied outside a cell. They appar- 

 ently originated as pieces of bacterial 

 chromosomes. 



Most bacteria have evolved the ability 

 to resist penicillin by acquiring a partner, a 



Complicating the treatment of gonorrhea, 

 some strains of the bacterium Neisseria 

 gonorrhoeae are no longer vulnerable to 

 penicillin and certain other antibiotics. 

 They have acquired their resistance by 

 incorporating bits of DNA from other 

 bacterial species — a process known as 

 genetic transfonnation. 



Photographs CNRI/Science Photo Library; Photo Researchers 



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