ReviewProteolysis in plasmid DNA stable maintenance in bacterial cells
Introduction
The concept of proteostasis assumes the existence of competing and integrated biological pathways that control the biogenesis, conformation, trafficking, concentration, binding interactions (quaternary structure), aggregation and degradation of all cellular proteins (Balch et al., 2008, Powers et al., 2009). The maintenance of protein homeostasis in cells is strictly controlled by cellular chaperones and proteases. It has been demonstrated for different plasmid systems that bacterial chaperones and proteases affect plasmid metabolism. Although plasmids are considered to be replicons independent from chromosomal DNA, proteins that are encoded on plasmids become a part of the cellular proteome that undergoes constant changes. The maintenance of an iteron containing plasmid in a bacterial population depends on its specific copy number which is affected by different processes including plasmid replication initiation, regulation of expression of rep gen, formation of a handcuff complex, plasmid multimer resolution (mrs), partitioning of plasmid particles into cells before cell division, and a toxin-antitoxin (TA) post-segregational killing (psk). These processes depend on the formation and dissociation of protein-protein as well as nucleoprotein complexes formed within the plasmid DNA and could be affected by bacterial molecular chaperones and especially proteases. The influence of proteases on some of the above mentioned processes is hypothetical i.e. dissociation of handcuff complex, obscure, i.e. segregation of plasmid particles to daughter cells (Inagawa et al., 2001), but in case of other i.e. plasmid replication initiation and plasmid type II TA there is more data, what we described below in the text (also see scheme presented in Fig. 1).
Section snippets
Cellular proteases
Cellular proteases are responsible for bacterial proteostasis maintenance. They carry out this function by degrading selected proteins, protein aggregates, and improperly folded proteins. Proteostasis maintenance requires degradation of regulatory proteins, which are involved in such processes as cell-cycle control (Iniesta et al., 2006), response to heat shock (Schweder et al., 1996), response to amino acid starvation (Kuroda et al., 2001), sporulation (Serrano et al., 2001), regulation of
Effects of proteolysis on plasmid replication initiation
The control of bacterial plasmid DNA replication enables the maintenance of a precise copy number of plasmid particles per cell. Under selective pressure, e.g. an antibiotic, this process is associated with host survival coupled with inheritance of at least one copy of a plasmid, which provides resistance to the antibiotic in each of the daughter cells after cell division. Plasmid replication depends on proteins encoded by the plasmid itself and by the host chromosome. Certain of these proteins
Effects of proteolysis on plasmid encoded type II toxin-antitoxin systems
TA systems are widespread among prokaryotes, but do not occur in eukaryotes (Park et al., 2013). Therefore, understanding the principles of how they function in bacterial cells may allow the development of a new tool for eradicating pathogenic and multi-resistant bacterial strains. TA systems are encoded on plasmids and also on the chromosomes of bacteria (reviewed in (Brzozowska and Zielenkiewicz, 2013, Gerdes and Maisonneuve, 2012, Ghafourian et al., 2014, Hernandez-Arriaga et al., 2014,
Concluding remarks
Plasmid copy number and thus plasmid maintenance is controlled by systems encoded directly by plasmid DNA. However, host encoded proteins, including molecular chaperones and proteases, affect the protein components of these systems. The redundancy of chaperones as well as proteases systems in bacterial cells has made studies on their effects difficult. Degradation of plasmid replication initiation proteins and antitoxin proteins has been described for plasmids. Noteworthy is the observation
Acknowledgements
This work was supported by Polish National Science Centre [grant number 2012/04/A/NZ1/00048]. Anna Karlowicz was supported by project MPD/2010/5 operated within the Foundation for Polish Science International PhD Projects (MPD) Programme co-financed by the EU European Regional Development Fund, Operational Program Innovative Economy 2007–2013.
We thank Dr. Aresa Toukdarian for critical reading of the manuscript.
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Authors have equal contribution.