Protein Aggregation is Associated with Acinetobacter baumannii Desiccation Tolerance

Abstract

Desiccation tolerance has been implicated as an important characteristic that potentiates the spread of the bacterial pathogen Acinetobacter baumannii on dry surfaces. Here we explore several factors influencing desiccation survival of A. baumannii. At the macroscale level, we find that desiccation tolerance is influenced by cell density and growth phase. A transcriptome analysis indicates that desiccation represents a unique state for A. baumannii compared to commonly studied growth phases and strongly influences pathways responsible for proteostasis. Remarkably, we find that an increase in total cellular protein aggregates, which is often considered deleterious, correlates positively with the ability of A. baumannii to survive desiccation. We show that inducing protein aggregate formation prior to desiccation increases survival and, importantly, that proteins incorporated into cellular aggregates can retain activity. Our results suggest that protein aggregates may promote desiccation tolerance in A. baumannii through preserving and protecting proteins from damage during desiccation until rehydration occurs.

Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment

“…In response to osmotic stress, A. baumannii also accumulates mannitol and glutamate; however, their contribution to desiccation resistance remains mostly unexplored [ 81 ]. To counteract the effects of oxidative stress, the expression of anti-oxidant enzymes, such as catalases KatE and KatG, superoxide dismutase, and glutathione peroxidase, is induced in desiccation-stressed A. baumannii [ 49 , 86 , 87 ]. A recent study by Farrow et al proved that the global BfmR regulator contributes to that desiccation tolerance [ 49 ].…”

“…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 ]. Wang 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 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 Δlon mutation. It was also demonstrated that the model proteins sequestered in the aggregates, β-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 ].…”

Protein aggregates carry non-genetic memory in bacteria after stresses

“…For prokaryotes, this issue is insufficiently covered. Protein homeostasis of various model and extremophilic species of bacteria (E. coli, C. crescentus, Clostridium botulinum, Acine to bacter baumannii etc) is currently being actively studied [10,[26][27][28][29][30]34]. The emerging data on the study of these model bacteria show that accumulation of PAs is directly related to the impact of stressors and population "ageing".…”

“…The emerging data on the study of these model bacteria show that accumulation of PAs is directly related to the impact of stressors and population "ageing". Increased protein aggregation is provoked by a heat shock, action of antibiotics (aminoglycosides) and antimicrobial peptides, depletion of the nutrient medium, oxidized stress, heavy metals, ultraviolet light, hydrostatic pressure, ionic strength, pH [24,32,[34][35][36] not provoke strong dispersion and lethality of the population [35,36]. Sublethal concentrations of aminoglycoside antibiotics such as kanamycin and streptomycin cause mRNA mistranslation, resulting in the creation of foldingdeficient protein species, which can induce aggregation [28].…”