Natural transformation is a widespread mechanism for genetic exchange in bacteria. Aminoglycoside and fluoroquinolone antibiotics, as well as mitomycin C, a DNA-damaging agent, induced transformation in Streptococcus pneumoniae . This induction required an intact competence regulatory cascade. Furthermore, mitomycin C induction of recA was strictly dependent on the development of competence. In response to antibiotic stress, S. pneumoniae , which lacks an SOS-like system, exhibited genetic transformation. The design of antibiotherapy should take into consideration this potential of a major human pathogen to increase its rate of genetic exchange in response to antibiotics.

Bacterial transformation, a programmed mechanism for genetic exchange originally discovered in Streptococcus pneumoniae, is widespread in bacteria. It is based on the uptake and integration of exogenous DNA into the recipient genome. This review examines whether induction of competence for genetic transformation is a general response to stress in gram-positive bacteria. It compares data obtained with bacteria chosen for their different lifestyles, the soil-dweller Bacillus subtilis and the major human pathogen S. pneumoniae. The review focuses on the relationship between competence and other global responses in B. subtilis, as well as on recent evidence for competence induction in response to DNA damage or antibiotics and for the ability of S. pneumoniae to use competence as a substitute for SOS. This comparison reveals that the two species use different fitness-enhancing strategies in response to stress conditions. Whereas B. subtilis combines competence and SOS induction, S. pneumoniae relies only on competence to generate genetic diversity through transformation.

We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes.

In vitro mariner transposon mutagenesis of Streptococcus pneumoniae chromosomal DNA was used to isolate regulatory mutants affecting expression of the comCDE operon, encoding the peptide quorum-sensing two-component signal transduction system controlling competence development. A transposon insertion leading to increased comC expression was found to lie directly upstream from the S. pneumoniae clpP gene, encoding the proteolytic subunit of the Clp ATP-dependent protease, whose expression in Bacillus subtilis is controlled by the CtsR repressor. In order to examine clp gene regulation in S. pneumoniae , a detailed analysis of the complete genome sequence was performed, indicating that there are five likely CtsR-binding sites located upstream from the clpE , clpP , and clpL genes and the ctsR - clpC and groESL operons. The S. pneumoniae ctsR gene was cloned under the control of an inducible promoter and used to demonstrate regulation of the S. pneumoniae clpP and clpE genes and the clpC and groESL operons by using B. subtilis as a heterologous host. The CtsR protein of S. pneumoniae was purified and shown to bind specifically to the clpP, clpC, clpE , and groESL regulatory regions. S. pneumoniae Δ ctsR , Δ clpP , Δ clpC , and Δ clpE mutants were constructed by gene deletion/replacement. ClpP was shown to act as a negative regulator, preventing competence gene expression under inappropriate conditions. Phenotypic analyses also indicated that ClpP and ClpE are both required for thermotolerance. Contrary to a previous report, we found that ClpC does not play a major role in competence development, autolysis, pneumolysin production, or growth at high temperature of S. pneumoniae .

Genetic plasticity plays a central role in the biology of the human pathogen Streptococcus pneumoniae. This is illustrated by the existence of at least 90 different capsular types (the polysaccharide capsule has an essential antiphagocytic function) as well as by the rapid emergence of penicillin‐resistant (Pen^R) pneumococcal isolates. Natural genetic transformation is believed to be essential for this genetic plasticity; capsular types can be switched by intraspecies transformation, whereas interspecies transformation is responsible for the appearance, in the Pen^R isolates, of mosaic pbp genes, which encode proteins with reduced affinity for penicillin. Data on the regulation of competence for transformation in S. pneumoniae, on the control of intra‐ and interspecies genetic exchange and on the shuffling and capture of exogenous sequences during transformation are reviewed. Possible links between transformation and changes in environmental conditions are discussed, and the adaptive ‘strategy’ deduced for S. pneumoniae is compared with that of Escherichia coli.