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Journal of Bacteriology, August 2002, p. 4392-4399, Vol. 184, No. 16
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.16.4392-4399.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Short-Sequence Tandem and Nontandem DNA Repeats and Endogenous Hydrogen Peroxide Production Contribute to Genetic Instability of Streptococcus pneumoniae

Christopher D. Pericone,1 Deborah Bae,1 Mikhail Shchepetov,1 Tera McCool,1 and Jeffrey N. Weiser1,2*

Departments of Microbiology,1 Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 191042

Received 22 January 2002/ Accepted 21 May 2002

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.

* Corresponding author. Mailing address: 402A Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: (215) 573-3511. Fax: (215) 898-9557. E-mail: weiser{at}mail.med.upenn.edu.

Journal of Bacteriology, August 2002, p. 4392-4399, Vol. 184, No. 16
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.16.4392-4399.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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