近日，來自Wageningen大學(xué)的研究者揭示了細(xì)菌對(duì)抗生素頭孢噻肟的耐藥性是可以提前進(jìn)行預(yù)測(cè)的,。很多研究表明細(xì)菌中由于許多基因的突變因此產(chǎn)生了對(duì)抗生素的耐藥性,，因此眾多抗生素的治療效果并不明顯,。和德國的研究者共同合作，Wageningen大學(xué)的研究者開發(fā)出了一種新的方法,，這種新型方法可以幫助我們預(yù)測(cè)耐藥菌株是否會(huì)對(duì)其它抗生素產(chǎn)生抗性,，以及如何產(chǎn)生抗性。相關(guān)研究成果刊登在了近日的國際雜志PLoS Genetics上,。
文章中,，研究者研究了細(xì)菌對(duì)抗生素頭孢噻肟產(chǎn)生抗性的主要酶類，β-內(nèi)酰胺酶類的主要功能就是破壞β-內(nèi)酰胺類抗生素,，研究者在對(duì)抗生素頭孢噻肟產(chǎn)生耐藥的菌株中發(fā)現(xiàn)了眾多突變,，β-內(nèi)酰胺酶類的突變提高了細(xì)菌對(duì)β-內(nèi)酰胺類抗生素耐藥性達(dá)3倍以上?；诖饲暗难芯?，研究者可以輕松地估計(jì)細(xì)菌的耐藥性效應(yīng)。
細(xì)菌中突變的存在使得科學(xué)家可以更容易預(yù)測(cè)抗生素耐藥菌株的產(chǎn)生以及發(fā)展,。研究者在數(shù)量上進(jìn)行了遺傳發(fā)現(xiàn)的研究,，運(yùn)用數(shù)學(xué)模型可以幫助研究者繼續(xù)深入研究，這樣一來研究者就能夠解釋細(xì)菌變得對(duì)抗生素產(chǎn)生耐藥,。通過研究者De Visser的方法,，科學(xué)家們可以預(yù)測(cè)細(xì)菌對(duì)于其它抗生素的“可維持性”（即什么時(shí)候產(chǎn)生耐藥）,。（生物谷Bioon.com）
編譯自：Development of Antibiotic Resistance More Predictable Than Expected
doi:10.1371/journal.pgen.1002783
PMC:
PMID:
Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme
Martijn F. Schenk1,2, Ivan G. Szendro3, Joachim Krug3,4, J. Arjan G. M. de Visser2*
For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance.
