Role of protein repair enzymes in oxidative stress survival and virulence of Salmonella

Abstract

Purpose Proteins are the principal biomolecules in bacteria that are affected by the oxidants produced by the phagocytic cells. Most of the protein damage is irreparable though few unfolded proteins and covalently modified amino acids can be repaired by chaperones and repair enzymes respectively. This study reviews the three protein repair enzymes, protein l-isoaspartyl O-methyl transferase (PIMT), peptidyl proline cis-trans isomerase (PPIase), and methionine sulfoxide reductase (MSR). Methods Published articles regarding protein repair enzymes were collected from Google Scholar and PubMed. The information obtained from the research articles was analyzed and categorized into general information about the enzyme, mechanism of action, and role played by the enzymes in bacteria. Special emphasis was given to the importance of these enzymes in Salmonella Typhimurium. Results Protein repair is the direct and energetically preferred way of replenishing the cellular protein pool without translational synthesis. Under the oxidative stress mounted by the host during the infection, protein repair becomes very crucial for the survival of the bacterial pathogens. Only a few covalent modifications of amino acids are reversible by the protein repair enzymes, and they are highly specific in activity. Deletion mutants of these enzymes in different bacteria revealed their importance in the virulence and oxidative stress survival. Conclusion PIMT repairs isoaspartate residues, PPiase catalyzes the conversion of cis-trans forms of proline residues, while MSR repairs oxidized methionine (Met) residues in the proteins. These repair enzymes maintain the activities of the target protein(s), thus aid in bacterial survival and virulence. The interventions which can interfere with this mechanism could be used for the development of novel therapeutics.

Manganese Utilization in Salmonella Pathogenesis: Beyond the Canonical Antioxidant Response

“…In addition, ROS carbonylate arginine, lysine, proline and threonine residues, and oxidize metal prosthetic groups and histidine residues ( Ortiz de Orue Lucana et al, 2012 ; Chang et al, 2020 ). Salmonella have evolved diverse mechanisms to counter ROS generation, prevent formation of hydroxy radicals, inhibit delivery of ROS into Salmonella -containing vesicles, detoxify and scavenge ROS, or repair the resultant protein and DNA modifications ( Buchmeier et al, 1995 ; De Groote et al, 1997 ; Vazquez-Torres et al, 2000a ; Vazquez-Torres et al, 2000b ; Gallois et al, 2001 ; Vazquez-Torres and Fang, 2001 ; Waterman and Holden, 2003 ; Halsey et al, 2004 ; Aussel et al, 2011 ; Bogomolnaya et al, 2013 ; Song et al, 2013 ; Rhen, 2019 ; Bogomolnaya et al, 2020 ; Shome et al, 2020 ). Of particular interest to this review, Mn 2+ protects Salmonella from ROS-mediated cytotoxicity by serving as a cofactor for SOD and KatN enzymes, replacing Fe 2+ in the active sites of mononuclear iron-containing enzymes, and acting as a nonproteinaceous antioxidant ( Culotta and Daly, 2013 ; Imlay, 2014 ; Ighodaro and Akinloye, 2018 ).…”

Cryptic niche differentiation of novel sediment ecotypes of Ruegeria pomeroyi correlates with nitrate respiration

“…Consistently, a few genes of these functional categories are part of the d S outliers. Examples involved in protein repair are pcm coding for l ‐isoaspartyl O‐methyl transferase, and slyD as well as surA for peptidyl‐prolyl cis‐trans isomerases (Shome et al ., 2020). Examples involved in glutathione metabolism include gshA encoding glutamate‐cysteine ligase that catalyses the first and rate‐limiting step in glutathione biosynthesis (Franklin et al ., 2009), ggt encoding an enzyme with both γ ‐glutamyl transpeptidase and hydrolase activity essential for utilization of exogenous glutathione (Suzuki et al ., 1999), and gst encoding glutathione S‐transferase acting to detoxify ROS (Kanai et al ., 2006).…”

“…All of these factors promote the formation of reactive oxygen species (ROS) (Freire et al ., 2011). In response to this oxidative stress, organisms have evolved several mechanisms including repair enzymes that restore protein functions (Shome et al ., 2020), antioxidant molecules such as glutathione that detoxify ROS (Masip et al ., 2006), and antioxidant enzymes such as catalase and peroxidase that convert ROS to stable nontoxic molecules (Imlay, 2013). Consistently, a few genes of these functional categories are part of the d S outliers.…”

A Novel Small RNA, DsrO, in Deinococcus radiodurans Promotes Methionine Sulfoxide Reductase ( msrA ) Expression for Oxidative Stress Adaptation

“…Compared to the ROS-sensitive E. coli , D. radiodurans has highly active protein repair systems to mitigate ROS damage and decrease oxidized protein and protein carbonylation. Because the Msr protein is a typical enzyme with the ability to repair oxidized Met ( 37 ), we investigated the function of MsrA in D. radiodurans and analyzed its regulatory mechanisms. Here, we report the function of MsrA in D. radiodurans during oxidative stress and show that msrA is regulated by both the sRNA DsrO and the transcription factor DrRRA to quickly respond to oxidative stress, improving the antioxidant ability of D. radiodurans compared to ROS-sensitive bacteria ( Fig.…”