An overview of moonlighting proteins in Staphylococcus aureus infection

Abstract

Staphylococcus aureus is responsible for numerous instances of superficial, toxin-mediated, and invasive infections. The emergence of methicillin-resistant (MRSA), as well as vancomycin-resistant (VRSA) strains of S. aureus, poses a massive threat to human health. The tenacity of S. aureus to acquire resistance against numerous antibiotics in a very short duration makes the effort towards developing new antibiotics almost futile. S. aureus owes its destructive pathogenicity to the plethora of virulent factors it produces among which a majority of them are moonlighting proteins. Moonlighting proteins are the multifunctional proteins in which a single protein, with different oligomeric conformations, perform multiple independent functions in different cell compartments. Peculiarly, proteins involved in key ancestral functions and metabolic pathways typically exhibit moonlighting functions. Pathogens mainly employ those proteins as virulent factors which exhibit high structural conservation towards their host counterparts. Consequentially, the host immune system counteracts these invading bacterial virulent factors with minimal protective action. Additionally, many moonlighting proteins also play multiple roles in various stages of pathogenicity while augmenting the virulence of the bacterium. This has necessitated elaborative studies to be conducted on moonlighting proteins of S. aureus that can serve as drug targets. This review is a small effort towards understanding the role of various moonlighting proteins in the pathogenicity of S. aureus.

Within-Host Adaptation of Staphylococcus aureus in a Bovine Mastitis Infection Is Associated with Increased Cytotoxicity

“…These cytosolic proteins have been described to be involved in various cellular biochemical processes. Since we detected these proteins at the cellular surface, they might exert additional functions in bacterial pathogenesis known as moonlighting function [37]. However, we found no evidence for this in the literature.…”

Impacts of the Type I Toxin–Antitoxin System, SprG1/SprF1, on Staphylococcus aureus Gene Expression

“…In conclusion, in laboratory conditions, deletion of the SprG1/SprF1 type I TA system has no effect on S. aureus growth, however, it induces noticeable changes in the proteome. Some of the affected proteins are bona fide virulence factors or are involved in metabolic traits and have moonlighting functions that could be linked to staphylococcal pathogenicity [ 49 ]. Our proteomic data point to SprF1 RNA as a possible gene expression regulator.…”

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

“…A well-characterized example is the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Streptococcus pyogenes or S. aureus . This enzyme is involved in adherence and internalization and thus directly serves as a virulence determinant for adhesion [ 60 , 61 ]. There is also an array of moonlighting proteins, with adhesive properties, in the yeast C. albicans , including enolase (ENO1), phosphoglycerate mutase 1 (GPM1), Ssa1 chaperoning, and GAPDH [ 62 , 63 , 64 ].…”

“…Proteolytic degradation of neuropeptides by microbial proteases, however, seems to be a different and more likely matter. The findings that various bacteria such as P. aeruginosa , E. faecalis , Proteus mirabilis , S. enterica , S. pyogenes , Burkholderia cenocepacia , Vibrio cholera and pathogenic yeasts such as C. albicans can cleave pivotal antimicrobial peptides including LL-37 appear to support this notion [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 …”