Although the resuscitation mechanism of VBNC cells remains largely unknown, studies examining resuscitation from the VBNC state have provided many promising results, and people have gradually acquired a greater understanding of the resuscitation mechanism with the development of molecular biology. Resuscitation promoting factor (Rpf), a highly conserved protein composed of 220 amino acids that is directly related to the resuscitation of VBNC cells, has been demonstrated to restore the growth and reproductive ability of VBNC cells (Mukamolova et al., 1998). Rpf proteins have been shown to act as cytokines that, when secreted into the medium by growing cells, bind to the surface receptors of dormant cells and trigger resuscitation (Pinto et al., 2015). Panutdaporn et al. (2006) also showed that the growth of S. enterica serovar Oranienburg cells could be enhanced by a certain concentration of rRpf protein. Moreover, Pinto et al. (2011) observed that Rpf supernatant fluid treated with proteinase K could resuscitate the VBNC cells of E. coli, suggesting that the breakdown products of Rpf could also restore VBNC cells. In addition, Pinto et al. (2013) validated the hypothesis that two Rpfs of L. monocytogenes, Lmo0186 and Lmo2522, could promote resuscitation via a mechanism analogous to actinobacteria Rpf proteins. Although the mechanism of Rpf in VBNC cell resuscitation is still not well understood, most researchers believe that the mechanism of Rpf is similar to that of lysozyme, both of which play a role in hydrolysis to divide the peptidoglycan in the cell wall (Keep et al., 2006a). There are two viewpoints regarding the mechanism of Rpf (Figure 2): one is that the breakdown product(s) of peptidoglycan by Rpf may interact with other factors and function as ‘second messengers’ to stimulate the resuscitation and growth of VBNC cells; the other is that Rpf is required to cleave peptidoglycans with inhibitory properties that are distributed in specific areas of the dormant cell wall and thus promote cell division and growth resumption (Keep et al., 2006b). To provide insights into the regulatory mechanism of Rpf protein, Aydin et al. (2011) obtained high-level expression of recombinant V. parahaemolyticus YeaZ in E. coli to determine the atomic structure and elucidate the three-dimensional structural conservation in YeaZ homologs, which may broaden perspectives regarding the mechanism of Rpf. However, the mechanism of Rpf and its breakdown products are still not clear and require further study.