Re: How does pH affect bacterial growth, in terms of the molecular processes?

Dear Eddie,
This is a really interesting question and one that is especially relevant
to modern health.  As I am sure you are well aware, bacterial resistance to
antibiotic therapies is emerging as a real concern in industrialized
countries, and understanding how bacteria behave on a molecular level is a
good place to start to understand how to fight infection.  I will try to
answer your question by giving three examples that can be more broadly
applied to A) general metabolic, B) nutritional and C) electrochemical
areas of thought.  Hopefully you can find more examples of each topic on
your own.
I will dive right into the question by quickly explaining how pH might
affect a protein.  You mention the word "denature" in your question, which
indicates to me that you probably know where this first part of the answer
is going.  Proteins rely on very specific interactions between their
constituent amino acids in order to properly fold.  The shape into which
they fold is the key factor in determining how a protein, an enzyme for
instance, behaves.  When pH changes, some atoms in the "R" groups (the side
chains) of amino acids can either accept a proton or give up a proton. 
Sulfur atoms (found in cysteine and methioneine) and oxygen atoms (notably
found in amino acids with hydroxyl groups, like serine, tyrosine and
threonine) are most likely to exhibit this change in ionization.  Because
changing the ionization state of an amino acid can change its chemical
behavior, these events are not trivial in regards to the final structure of
a protein.  A good example can be found in proteins that contain disulfide
bonds between cysteines.  The function of a protein could be entirely
dependent upon an intact disulfide bond, but under acidic conditions the
disulfide bond reverts to two -SH groups.  Because enzymes are largely
responsible for every metabolic reaction in a cell, bacterial and
otherwise, altering their behavior by changing the pH can dramatically
reduce the viability of the bacteria.  
Just like amino acids can be ionized in certain pH conditions, so can
micronutrients required for bacterial growth.  Iron, for instance, is
required as an enzyme cofactor by bacteria.  Bacteria have devised some
ingenious methods for scavenging iron from their hosts.  One method uses
secreted iron-binding proteins called siderophores.  Siderophores tightly
bind iron and then the bacteria are able to reabsorb it.  The catch is,
only ferric (3+) iron binds tightly to siderophores.  Ferrous (2+) iron
does not.  Under acidic conditions, such as in the stomach, iron is reduced
to ferrous and does not bind to siderophores.  In the mouth, though, the pH
is less acidic and both ferric and ferrous iron exists.  If ferric iron is
excluded from this environment, it will be more difficult for bacteria to
absorb enough iron to flourish.  
Finally, bacteria use electrochemical gradients across their membranes to
drive some physiological processes.  I will use drug resistance as an
example.  If you treat bacteria with tetracycline, an antibiotic, it will
cross the plasma membrane into the bacterium and bind to ribosomes,
preventing them from creating proteins.  Some bacteria have caught onto
this trick, though, and devised a method for resisting the effects of
tetracycline by literally pumping it back out of their membranes.  To do
this, they have special drug efflux pumps.  These pumps can use ATP as a
source of energy, but more often than not they are proton motive force
driven.  This concept depends on the outside of the cell having more
protons (lower pH, of course) than the inside of the cell.  This creates an
electrochemical gradient.  Free energy is lowered by allowing protons to
enter the cell.  By controlling how, when, and where the protons enter, the
bacteria can harvest some of that free energy.  In this case, the protons
cross the membrane at these specialized pumps, which use the free energy to
push the tetracycline out of the cell.  If pH inside the bacterium was too
high, or pH outside the bacterium was too low, there would be insufficient
energy gained from letting protons into the cells; the proton motive force
would dissipate and the efflux pumps would no longer drive tetracycline out
of the cells.  
I hope these three examples help answer your question - and good luck on
your project!

Sincerely,
Billy Carver


MI Borges-Walmsley, KS McKeegan, and AR Walmsley.  "Stucture and function
of efflux pumps that confer resistance to drugs."  Biochemical Journal. 
376.  2003.

S Sarker, G Fuchs. "Helicobacter pylori infection, iron absorption, and
gastric acid secretion in Bangladeshi children."  American Journal of
Clinical Nutrition.  80(1).  2004.

M Miethke, M Marahiel.  Siderophore-based Iron Acquisition and Pathogen
Control.  Microbiology and Molecular Biology Reviews.  71(3).  2007.