Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

Abstract

Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics.

Metabolite Profiling of Malaysian Gracilaria edulis Reveals Eplerenone as Novel Antibacterial Compound for Drug Repurposing Against MDR Bacteria

“…This protein is a bacterial molecular chaperone of the Heat Shock Protein 70 kDa (HSP70) family which mediates bacterial survival under stress conditions, especially antibiotic administration ( Singh et al, 2012 ). It has been proposed as an attractive druggable target as well as a vaccine candidate ( Fourie and Wilson, 2020 ). Moreover, DnaK has also been identified to be important in quorum sensing, as well as cellular integrity in bacteria by other studies ( Pawar et al, 2018 ; Mujawar et al, 2020 ).…”

Utilizing a reductionist model to study host-microbe interactions in intestinal inflammation

“…ClpB and DnaK are chaperones that work together to solubilize and refold protein aggregates that can form during stress [ 51 , 52 ]. They have also been shown to be important for motility and virulence in several different bacteria, and DnaK is immunogenic [ 53 – 58 ]. Furthermore, levels of DnaK and ClpB are increased in the intestinal bacterial proteomes of Crohn’s patients [ 59 ].…”

Helicobacter pylori Infection and Extragastric Diseases—A Focus on the Central Nervous System

“…These higher levels correlated positively with Expanded Disability Status Scale (EDSS) and duration of illness, especially in secondary progressive multiple sclerosis (SPMS), and were proposed to be used as disease progression biomarkers [ 107 ]. Heat shock proteins (HSPs) are present in both prokaryotic and eukaryotic organisms as one of the most evolutionary conserved proteins with possible immunogenic properties [ 108 ]. In a healthy organism, the own HSPs do not promote an immunological response; however, there are some data about their involvement in autoimmunity.…”

“…Interestingly, both prokaryotic and eukaryotic HSPs share some epitopes, and, consequently, this may promote cross-reactivity. Nevertheless, this topic still remains unclear [ 108 ]. There is also an observation of the overexpression of HSPs of the HSP70 family in MS patients’ brains.…”