Short-sequence tandem and nontandem DNA repeats and endogenous hydrogen peroxide production contribute to genetic instability of Streptococcus pneumoniae.
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.
Pericone
Christopher D
CD
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
Bae
Deborah
D
Shchepetov
Mikhail
M
McCool
Tera
T
Weiser
Jeffrey N
JN
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D016368:Frameshift Mutation / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008969:Molecular Sequence Data; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011771:Pyruvate Oxidase / Q000235:genetics; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000378:metabolism*; D020080:Tandem Repeat Sequences / Q000235:genetics
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C119769:LicD2 protein, Streptococcus pneumoniae; C069816:phage shock protein, Bacteria; D006861:Hydrogen Peroxide; D011771:Pyruvate Oxidase; C059639:DNA modification methylase XbaI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); C076332:EJL amidase; D009238:N-Acetylmuramoyl-L-alanine Amidase