This characteristic inter- and intra-strain homogeneity is unique among all the main outer membrane constituents, which, contrary to PIII, evolved a strong variability to escape the immune pressure of the host [7, 8]. PIII has been mainly studied for its peculiarity to induce “blocking antibodies” able to prevent the formation of the lytic complement attack complex and blocking the bactericidal activity of antibodies raised against other surface antigens [9, 10]. The ability to construct a viable
gonococcal mutant Idasanutlin lacking the pIII gene was described by Wetzler and collaborators in 1989. In that study the F62 Neisseria gonorrhoeae strain knocked-out for the pIII gene resulted to be identical to the wild-type strain in terms of competence, porin activity, protease and antibiotic sensitivity. The mutant had minimal differences in colony morphology and was slightly decreased in growth compared to the parent strain [11]. PIII is 95% GSK2118436 identical to class 4 protein of Neisseria meningitidis, also named RmpM (reduction modifiable protein M) for the characteristic migration in SDS-PAGE in presence of reducing agents [12]. The presence of RmpM in oligomeric
complexes of the outer membrane has been extensively described, with RmpM transiently associated to the porins, depending on the specific transport needs during the different stages of meningococcal life cycle [13, 14]. Moreover, RmpM forms heterooligomeric complexes with iron limitation-inducible OMPs [15] and associates through the N-terminal domain RVX-208 to the Omp85 complex [16]. The C-terminal region of PIII shows high similarity to the outer membrane protein A (OmpA) of E. coli and other Gram-negative bacteria [17]. OmpA has been studied in E. coli as a key factor in many pathogenicity processes. The expression of OmpA contributes to the structural integrity of the outer membrane [18] and confers a significant selective
advantage during the pathogenesis in vivo; an ompA mutant showed indeed an attenuated virulence in two different models of E. coli K1 infection and increased sensitivity to serum bactericidal activity [19]. The crystal structure of the OmpA-like domain of the meningococcal RmpM has been solved [20] revealing the presence of a C-terminal peptidoglycan-binding domain, which could stabilize the neisserial outer membranes promoting the tight interaction between the outer membrane and the peptidoglycan layer. To further expand the findings of Wetzler et al. [11] and unravel the role of PIII in the physiology of gonococci, we applied microscopy and biochemical approaches.