## 4 Protein Homeostasis in _A. baumannii_  
Upon oxidative stress, proteins, which are the main target of ROS, are damaged by metal-catalyzed oxidation and non-enzymatic glycation [79; 82; 89]. During desiccation, these detrimental reactions are facilitated by the reduction of the hydration shell around proteins and protein condensation, which in turn may lead to misfolding and aggregation of proteins. Apart from anti-oxidant enzymes, bacteria evolved additional mechanisms that protect proteins, including molecular chaperones and proteases. The main role of molecular chaperones is maintaining protein homeostasis (proteostasis), i.e., a proper balance of protein synthesis, folding, transport, and degradation [90]. Molecular chaperones are highly conserved among prokaryotes and, under stress conditions, they prevent aggregation of unfolded proteins, facilitate degradation of irreversibly misfolded proteins by proteases, and enable solubilization of protein aggregates for subsequent refolding or degradation [91; 92]. The key molecular chaperones in bacteria include the heat-shock protein 70 (Hsp70) family chaperone DnaK, its DnaJ (Hsp40) co-chaperone, and the nucleotide exchange factor GrpE, as well as the chaperonin GroEL (Hsp60) and its co-chaperone GroES (Hsp10). The efficient solubilization of aggregated proteins requires the cooperation of the DnaK-DnaJ-GrpE system with ClpB (Hsp100), IbpA/B (the small Hsp family), or Hsp33, which is the primary chaperone redox-activated upon oxidative stress. Most of these chaperones were found to be upregulated in _A. baumannii_ submitted to stresses that impair homeostasis: heat shock (DnaK, GroEL), oxidative stress (GrpE, DnaK, GroES, GroEL), antibiotic exposure (DnaK, GroEL), and desiccation (TF, GroES, GrpE, DnaJ, DnaK, ClpX, ClpB) [18; 86; 87; 93; 94]. [PERSON] et al. reported that the expression of more than 50 genes encoding proteins related to proteostasis, including chaperones and the Lon protease, was increased during desiccation [86]. The induction of proteins involved in the proteostasis system was accompanied by protein aggregation. Surprisingly, the accumulation of protein aggregates correlated positively with the ability of _A. baumannii_ to survive desiccation. The survival rate was also increased when protein aggregation was induced prior to desiccation by a subinhibitory concentration of streptomycin, or it was enhanced by the \(\Delta\)_lom_mutation. It was also demonstrated that the model proteins sequestered in the aggregates, \(\beta\)-lactamase and GFP, retained their activities [86]. These results are in agreement with previous studies showing that bacterial inclusion bodies contain functional proteins, and they confirm that aggregates may serve as compartments that protect proteins against inactivation [95; 96]. Upon desiccation, the sequestration of native molecules into aggregates may be favored due to the gradual concentration of proteins. In contrast, high temperatures or other stressors that cause fast and abundant protein misfolding may lead to decreased survival or cell death due to the formation of aggregates enriched in non-functional proteins. Recent studies showed that the induction of protein aggregation and disturbance of proteostasis may be an efficient strategy to kill pathogenic bacteria. [PERSON] et al. identified several peptides that induced bactericidal protein aggregation in _Escherichia coli_ and _A. baumannii_[97]. The peptides contained aggregation-prone sequences (APRs) that naturally occur in hydrophobic cores of globular proteins or on protein-protein interaction surfaces. When aggregation was nucleated in bacteria by the peptides containing APRs, it led to the lethal formation of inclusion bodies containing hundreds of proteins. The quaternary amine compounds (QACs), including benzalkonium chloride (BZK), can also trigger protein aggregation in _A. baumannii_ when used at low concentrations [98]. QACs are commonly used biocides that, at high concentrations, disrupt membranes.