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Abercrombie.v438 - NATURE|Vol 438|10 November 2005 NEWS...

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NATURE | Vol 438 | 10 November 2005 NEWS & VIEWS 171 antibiotics does not necessarily mean that resistance will become a widespread problem. Antibiotic resistance often compromises the bacteria in other ways — for example, by reducing their growth rate 8 . This means that antibiotic-sensitive bacteria will outcompete the resistant forms when neither is exposed to the antibiotic. Perron et al. 1 investigated this possibility, and indeed found a ‘cost’ of antibiotic resistance: in the absence of the antibiotic, resistant bacteria took longer to start reproducing than control bacteria, although once they had got going, their repli- cation rate was unaffected. Unfortunately, bacteria have other tricks up their sleeves. In addition to adapting to anti- biotics, they can also adapt to antibiotic resis- tance. There have been numerous cases of bacteria with antibiotic resistance developing mutations in other parts of their genome that compensate for the associated costs 8,9 . These adaptations are sometimes so specific that the growth rate of bacteria can decrease if the genetic changes conferring antibiotic resis- tance are replaced with the original sensitive form of the gene after compensatory adapta- tion has occurred 9 . Why should bacterial resistance to RAMPs cause more concern than resistance to other antibiotics? The major problem will be if resis- tance to chemotherapeutic RAMPs also con- fers resistance to naturally occurring RAMPs in humans and other organisms. Bacteria that are normally dealt with unnoticed by our innate immune system may then cause serious infections. Large-scale use of chemotherapeu- tic RAMPs may ultimately help pathogenic bacteria colonize parts of animals and plants that were previously off limits to them. This perspective may be overstating the case for concern. Humans alone produce a highly diverse arsenal of RAMPs, which are also thought to be constantly evolving new ways of targeting bacteria 1 ; and RAMPs constitute only one part of our natural immunity. Fur- thermore, RAMP resistance, where observed, is often specific to a small range of RAMPs 4 . There are exceptions, however. A variety of bacteria, including Staphylococcus aureus famed for methicillin resistance — and the opportunistic pathogen Pseudomonas aerugi- nosa have evolved a degree of generalized RAMP resistance by increasing the amount of positively charged protein in their mem- branes. The consequence may be to reduce the binding efficiency of the positively charged RAMPs 10 . As Perron et al. 1 , and others 2–4 , emphasize, RAMPs are likely to make a major contribu- tion to human health and agriculture. But given the prospect of resistance, extra caution is necessary in developing and using them. Angus Buckling is in the Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
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