Response to Ambur et al.

 The points in purple are objections raised by Ambur et al. to the hypothesis that the main function of DNA uptake by competent bacteria is acquisition of DNA as a nutrient:

These points are typical of those raised when the goal is to dismiss the nutrient hypothesis rather than to carefully consider all the issues.

 

(i) As yet, there is no clear evidence that the integration of nucleotides taken up by transformation become routed into DNA metabolism.

Yes. Competence has mainly been studied in mucosal commensals, where investigations of metabolism are difficult.  In these organisms absence of evidence is not evidence of absence.

(ii) The presence of exogenous DNA does not appear to induce competence in any transformable species.

Yes, but I don’t see why this is more relevant for the nutrient hypothesis than for other hypotheses.  (Also, Vibrio does use chitin as a signal for competence; its presence indicates biofilms and abundant DNA.)

(iii) Competence in streptococci, like S. pneumoniae, is induced for only a short time period during exponential growth when other resources are highly abundant.

Because laboratory growth conditions for human commensals and pathogens are so different from natural growth conditions, lab cultures are very poor guides to what matters in the real world.  That’s why our work focused on understanding the regulatory machinery.

(iv) Transported DNA is heavily protected against nuclease digestion within the cell, potentially enabling transported fragments to remain intact as a substrate for recombination.

And yet most competent bacteria take up all DNAs they encounter, and DNA that cannot be recombined is efficiently degraded.  The proteins that protect the DNA are also common in non-competent species and so must function outside of transformation.

(v) The hypothesis does not explain why several competent species only take up DNA from close relatives due to conserved DNA uptake sequences (USS and DUS) despite the fact that non-homologous DNA could be used as a source of nucleotides for direct use or degradation.

On the flip side, almost all competent bacteria take up DNA indiscriminately, so DNA’s benefit can’t depend on its information content.  For these exceptions, we have hypothesized that sequence-dependent uptake constraints exist in these species, and have shown that these create molecular drive that causes uptake sequences to accumulate in genomes at frequencies and distributions corresponding to those seen in real genomes with DUS and USS.