Systematic Assessment of Accessibility to the Surface of <i>Staphylococcus aureus</i>

Ferraro, Noel J.; Kim, Seonghoon; Im, Wonpil; Pires, Marcos M.

doi:10.1021/acschembio.1c00604

Cited by 18 publications

(27 citation statements)

References 71 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding Gram-positive bacteria, peptidoglycan and LTA have been reported to act as either peptide ‘sponges’, increasing their local concentration, or as peptide ‘traps’, keeping them away from the lipid membrane (Malanovic and Lohner, 2016a). A recent study strongly suggested that WTA and LTA strongly impeded the access of variable molecules to the surface of S. aureus membrane (Ferraro et al ., 2021).…”

Section: Trp-containing Amps and Glycoconjugatesmentioning

confidence: 99%

Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides

Khemaissa

Walrant

Sagan

2022

Quart. Rev. Biophys.

View full text Add to dashboard Cite

Trp is unique among the amino acids since it is involved in many different types of noncovalent interactions such as electrostatic and hydrophobic ones, but also in π-π, π-cation, π-anion and π-ion pair interactions. In membranotropic peptides and proteins, Trp locates preferentially at the water-membrane interface. In antimicrobial or cell-penetrating peptides (AMPs and CPPs respectively), Trp is well-known for its strong role in the capacity of these peptides to interact and affect the membrane organisation of both bacteria and animal cells at the level of the lipid bilayer. This essential amino acid can however be involved in other types of interactions, not only with lipids, but also with other membrane partners, that are crucial to understand the functional roles of membranotropic peptides. This review is focused on this latter less known role of Trp and describes in details, both in qualitative and quantitative ways: (i) the physico-chemical properties of Trp; (ii) its effect in CPP internalisation; (iii) its importance in AMP activity; (iv) its role in the interaction of AMPs with glycoconjugates or lipids in bacteria membranes and the consequences on the activity of the peptides; (v) its role in the interaction of CPPs with negatively charged polysaccharides or lipids of animal membranes and the consequences on the activity of the peptides. We intend to bring highlights of the physico-chemical properties of Trp and describe its extensive possibilities of interactions, not only at the well-known level of the lipid bilayer, but with other less considered cell membrane components, such as carbohydrates and the extracellular matrix. The focus on these interactions will allow the reader to reevaluate reported studies. Altogether, our review gathers dedicated studies to show how unique are Trp properties, which should be taken into account to design future membranotropic peptides with expected antimicrobial or cell-penetrating activity.

show abstract

Section: Trp-containing Amps and Glycoconjugatesmentioning

confidence: 99%

Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides

Khemaissa

Walrant

Sagan

2022

Quart. Rev. Biophys.

View full text Add to dashboard Cite

show abstract

“…From these data, we were able to further demonstrate the binding propensity of P1fl to The accessibility of immune proteins to its bacterial cell wall target is largely mitigated by the presence of large surface polymers, wall teichoic acid (WTA) and lipoteichoic acid (LTA). Our lab, 76 and others, [77][78][79][80] have recently demonstrated that WTA play a major contribution to the accessibility of molecules to the PG of bacterial cells;…”

Section: Resultsmentioning

confidence: 84%

“…The accessibility of immune proteins to its bacterial cell wall target is largely mitigated by the presence of large surface polymers, wall teichoic acid (WTA) and lipoteichoic acid (LTA). Our lab, 76 and others, [77][78][79][80] have recently demonstrated that WTA play a major contribution to the accessibility of molecules to the PG of bacterial cells; therefore, we aimed to investigate the role that WTA plays on the accessibility of P1fl to the surface of E. faecalis, as WTA is the most highly abundant glycopolymer on the enterococci cell wall. 81,82 To achieve this, sacculi isolated from E. faecalis were treated with acid to hydrolyze the phosphodiester linkage between WTA and the PG, effectively removing the WTA from the isolated PG.…”

Section: Resultsmentioning

confidence: 99%

Immuno-targeting of Gram-positive Pathogens via a Cell Wall Binding Tick Antifreeze Protein

Dalesandro

Pires

2022

Preprint

Self Cite

View full text Add to dashboard Cite

The human immune system employs several mechanisms to defend against pathogenic bacteria. However, pathogenic bacterial cells have evolved means to counter these responses, rendering our immune system less effective. Immunological agents that supplement or modulate the host immune response have proven to have powerful therapeutic potential, although this modality is less explored against bacterial pathogens. We describe the application of a bacterial binding protein to re-engage the immune system towards pathogenic bacteria. More specifically, a hapten was conjugated to a protein expressed by Ixodes scapularis ticks, called Ixodes scapularis antifreeze glycoprotein (IAFGP), that has high affinity for the D-alanine residue on the peptidoglycan of the bacterial cell wall. We showed that a fragment of this protein retained high surface binding affinity. Moreover, when conjugated to a hapten this conjugate led to the display of haptens on the cell surface of vancomycin-resistant Enterococcus faecalis. Hapten display then induced the recruitment of antibodies and promoted immune-cell mediated uptake of bacterial pathogens. These results demonstrate the feasibility in using cell wall binding agents as the basis of a class of bacterial immunotherapies against bacterial pathogens.

show abstract

“…The basis of the screening assay is site-specific incorporation of a biorthogonal handle via metabolic remodeling of bacterial PG. 11 More specifically, an unnatural amino acid (D-LysAz) is supplemented in the media, inoculated with S. aureus, and cultured overnight (Figure 2A). During PG biosynthesis and assembly, transpeptidases catalyze the replacement of the fifth position D-alanine on the stem peptide within the bacterial PG scaffold for D-LysAz, thus leading to the covalent installation of the azido-handle (Figure 2B).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…9,10 It was proposed that BPEI neutralization of negatively charged polymers on the bacterial cell surface improved permeability. 11 These examples demonstrate that improved permeation to the essential cell wall components can be a powerful modality of reducing intrinsic resistance to small molecule antibacterials and immune proteins. 12 The cell walls of bacteria are complex in structure and composition.…”

mentioning

confidence: 99%

Genetic Determinants of Surface Accessibility in Staphylococcus aureus

Ferraro

Pires

2022

Bioconjugate Chem.

Self Cite

View full text Add to dashboard Cite

Bacterial cell walls represent one of the most prominent targets of antibacterial agents. These agents include natural products (e.g., vancomycin) and proteins stemming from the innate immune system (e.g., peptidoglycan-recognition proteins and lysostaphin). Among bacterial pathogens that infect humans, Staphylococcus aureus (S. aureus) continues to impose a tremendous healthcare burden across the globe. S. aureus has evolved countermeasures that can directly restrict the accessibility of innate immune proteins, effectively protecting itself from threats that target key cell well components. We recently described a novel assay that directly reports on the accessibility of molecules to the peptidoglycan layer within the bacterial cell wall of S. aureus. The assay relies on site-specific chemical remodeling of the peptidoglycan with a biorthogonal handle. Here, we disclose the application of our assay to a screen of a nonredundant transposon mutant library for susceptibility of the peptidoglycan layer with the goal of identifying genes that contribute to the control of cell surface accessibility. We discovered several genes that resulted in higher accessibility levels to the peptidoglycan layer and showed that these genes modulate sensitivity to lysostaphin. These results indicate that this assay platform can be leveraged to gain further insight into the biology of bacterial cell surfaces.

show abstract

Systematic Assessment of Accessibility to the Surface of Staphylococcus aureus

Cited by 18 publications

References 71 publications

Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides

Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides

Immuno-targeting of Gram-positive Pathogens via a Cell Wall Binding Tick Antifreeze Protein

Genetic Determinants of Surface Accessibility in Staphylococcus aureus

Contact Info

Product

Resources

About