Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae

Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae
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DOI:
10.1128/jb.184.16.4392-4399.2002
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发表时间:
2002-08-01
影响因子:
3.2
通讯作者:
Weiser, JN
Weiser, JN
中科院分区:
生物学3区
文献类型:
--
作者:
Pericone, CD;Bae, D;Weiser, JN

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检测并分析了以下7种肺炎球菌基因的功能缺失突变:pspA、spxB、xba、licD 2、lytA、nanA和atpC。与这些突变相关的因素包括(i)由短至6个碱基的同聚重复内的单个碱基的可逆获得和丢失引起的移码,(ii)由短至8个碱基的非串联直接重复之间的重组事件引起的缺失,和(iii)由高水平的过氧化氢(>2 mM)以增加的频率引起的鸟嘌呤残基的取代通常由该物种在需氧生长条件下产生。后者占自发突变的频率高达2.8 × 10 ~(-6),对optochin耐药,在没有可检测水平的H_2O_2时低10 ~ 200倍。这些突变中的一些似乎已被选择在体内肺炎球菌感染期间,可能是由于免疫压力或氧化应激。
Loss-of-function mutations in the following seven pneumococcal genes were detected and analyzed: pspA, spxB, xba, licD2, lytA, nanA, and atpC. Factors associated with these mutations included (i) frameshifts caused by reversible gain and loss of single bases within homopolymeric repeats as short as 6 bases, (ii) deletions caused by recombinational events between nontandem direct repeats as short as 8 bases, and (iii) substitutions of guanine residues caused at an increased frequency by the high levels of hydrogen peroxide (>2 mM) typically generated by this species under aerobic growth conditions. The latter accounted for a frequency as high as 2.8 X 10(-6) for spontaneous mutation to resistance to optochin and was 10- to 200-fold lower in the absence of detectable levels of H2O2. Some of these mutations appear to have been selected for in vivo during pneumococcal infection, perhaps as a consequence of immune pressure or oxidative stress.