Role of Penicillin-Binding Proteins in the Viability, Morphology, Stress Tolerance, and Pathogenicity of .

Previous research has shown that penicillin-binding proteins (PBPs), enzymes involved in peptidoglycan (PG) assembly, could play an important role during the induction of the viable but nonculturable (VBNC) state, which allows non-spore-forming bacteria to survive adverse environmental conditions. The current study found that has seven PBPs. Mutant analysis indicated that deletion of either of the class B PBPs was lethal and that the class A PBPs had an important role in PG synthesis, with the Δ mutant having an altered cellular morphology that resulted in longer cells that were swollen at one end and had thinner cell walls. The mutant was also found to produce mucoid colonies in solid culture and a lower final cell titer in liquid medium, as well as having high sensitivity to osmotic stress and lysozyme treatment and surprisingly high pathogenicity. The double mutant, , also had a slightly altered phenotype, resulting in longer cells. Further analysis revealed that both mutants had high sensitivity to copper, which resulted in quicker induction into the VBNC state. However, only the mutant had significantly reduced survivorship in the VBNC state. The study also confirmed that the VBNC state significantly improved the survivorship of wild-type cells in response to environmental stresses and systemically demonstrated the protective role of the VBNC state in , which is an important finding regarding its epidemiology and has serious implications for disease management.