The VacA structure comprises five regions of sequence diversity referred to as the signal (s), intermediate (i) middle (m), deletion (d), and c (c) regions. The vacuolating activity of VacA varies with different alleles. In vitro, vacA s1/m1/i1 alleles show higher levels of vacuole formation than s2/m2/i2. The functions of novel polymorphic regions c and d, as well as the i3 subtype, have not yet been studied.