In the present study, we have validated the determination of mutation frequency (proportion of mutants in a culture) as an estimation of the amount of mutation occurring by determining mutation rate (number of mutations per cell division) in a proportion of isolates. We have also developed a novel rapid screening method that may be useful to others. Results of the study do not support an association between multiple antibiotic resistance and elevated frequency of mutation. This parallels previous observations that penicillin resistance or resistance to other antimicrobial agents is not associated with hypermutability in pneumococci,in contrast to reports in other species.
No frank mutators were detected, either among the 27 isolates for which full mutation frequencies were determined or among a further 180 isolates subject to a rapid detection screen, and only 2/27 (7.4%) had relatively high mutation frequencies. By comparison,two previous investigations had suggested 12.5% (2/16) and 20% of clinical S. pneumoniae to be hypermutable [2,22]. However,
in neither investigation could the elevated mutation frequency be accounted for by defects inMMRgenes as observed in other species [substitutions in HexA and HexB putatively implicated in hypermutability by Gould et al.  are also found in isolates with normal levels of mutation (Henderson-Begg, Livermore and Hall, unpublished data)].
Morosini et al.  and del Campo et al.  suggest that there is a bimodal distribution of mutation frequency among pneumococci,with mutators forming a distinct population.Wepostulate that this finding is due to an anomaly in the presentation of mutation frequency data. These authors have plotted a frequency distribution on a scale that is a mixture of arithmetic intervals and logarithmic
intervals so that isolates are grouped in the form 1–2.5, 2.5–5,5–7.5, 7.5–10, then 10–25, 25–50, etc.
Hence, the groups are not equal either on an arithmetic or logarithmic scale. This artefact generates an apparent bimodal distribution due to the lower numbers in the interval 7.5–10 (covering a 1.33-fold range)
relative to 10–25 (covering a 2.5-fold range)—a similar distribution was obtained with the data presented here when plotted in the same way.
Although this makes no difference to their conclusion regarding resistance, it has led to the widespread reporting of a distinct population of mutators in the species, which appears to be unjustified.
Hence, whilst there are clearly isolates of pneumococci that have mutation frequencies at the high end of the normal spectrum,and these may be enriched in certain situations, we do not believe that there is yet firm evidence of a genetically or phenotypically distinct mutator population
Our finding does not rule out the possibility that isolates were hypermutable at the time of acquisition of resistance and subsequently reverted to a level of mutability within the normal range because of the long-term disadvantage of elevated mutation rates Funding:
This work was supported by Barts and The London Charity.
Competing interests: None declared.
Ethical approval: Not required.
- 黑夜繁星Lv 69 年前最佳解答
沒有坦誠的存取器進行了檢測，其中27株或者為其全突變頻率分別確定或180株之間進一步受到快速檢測屏幕，只有2 / 27（7.4％）有相對較高的突變頻率。相比之下，前兩次調查中所建議的12.5％（2 / 16）和20％的肺炎鏈球菌為臨床高突變 [2,22]。然而，
既不調查可能升高的突變頻率進行核算的缺陷inMMRgenes在其他物種的觀察 [替換的六溴和HexB公認牽連 hypermutability古爾德等人。 也發現在株與正常水平的突變（恆基兆業，貝格，利弗莫爾和霍爾，未發表數據）]。
Morosini等。 和戴爾坎普等。 表明，有一個雙峰分佈的突變頻率在肺炎雙球菌，具有存取器形成了鮮明 population.Wepostulate發現，這是由於在演示文稿中的一個異常的突變頻率數據。這些作者們繪製的頻率分佈，其規模是一種混合物的算術和對數間隔
因此，這些組織不等於無論是在算術運算或對數刻度。這個人工製品產生一個明顯的雙峰分佈由於較低的號碼在區間 7.5-10（佔地 1.33倍範圍）
相對於 10-25（包括一個 2.5倍範圍內），一個類似的分佈，得到的數據繪製在這裡時，以同樣的方式。
因此，雖然有明確分離的肺炎鏈球菌具有突變頻率在高端正常譜，這些可能是富集某些情況下，我們不認為有沒有確鑿的證據或表型的基因突變 population distinct