How low can you go?...
In general, the lowest I'd opt for a defense caliber is .380acp or a .38spl +P.
A .22LR, .25acp, .32acp, etc is just small. Some "magnum" rounds may add punch but I'd trust my life or the life-safety of a close loved one to a .38spl +P or a .380acp(at a min).
My concern for the forum member/spouse is that she can handle any semi-auto pistol(slide, mag, controls, etc) or be able to fire/aim a loaded DA only revolver.
Some women(and men) can not.