Development and utilization of peptide-based quorum sensing modulators in Gram-positive bacteria

McBrayer, Dominic; Cameron, Crissey D; Tal‐Gan, Yftah

doi:10.1039/d0ob01421d

Cited by 37 publications

(34 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 Thus, knowledge about AIP structures is crucial for probing the molecular mechanisms of QS and pharmacological aspects of QS inhibition. 11 We recently developed a simple and robust procedure for enrichment of thiolactone-containing AIPs from complex bacterial supernatant, which facilitated the structural elucidation of a number of staphylococcal AIPs. 12 This method is predicated on the chemoselective trapping of thiolactones by resin-bound cysteine residues through a native chemical ligation (NCL) 13 like transformation.…”

mentioning

confidence: 99%

Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides

et al. 2021

View full text Add to dashboard Cite

Group behavior in many bacteria relies on chemically induced communication called quorum sensing (QS), which plays important roles in regulation of colonization, biofilm formation, and virulence. In Gram-positive bacteria, QS is often mediated by cyclic ribosomally synthesized and posttranslationally modified peptides (RiPPs). In staphylococci for example, most of these socalled autoinducing peptides (AIPs) contain a conserved thiolactone functionality, which has been predicted to constitute a structural feature of AIPs from other species as well. Here, we show that pentameric AIPs from Lactobacillus plantarum, Clostridium perfringens, and Listeria monocytogenes that were previously presumed to be thiolactone-containing structures readily rearrange to become homodetic cyclopeptides. This finding has implications for the developing understanding of the cross-species communication of bacteria and may help guide the discovery of peptide ligands to perturb their function. ASSOCIATED CONTENT Supporting InformationThe Supporting Information is available free of charge. Supplementary methods, schemes, figures and tables as well as copies of HPLC traces, 1 H and 13 C NMR spectra (PDF)

show abstract

mentioning

confidence: 99%

Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Substantial efforts have been made to develop anti-QS inhibitors, and a lot of new anti-QS inhibitors have been reported [29,68]. Peptide-based quorum sensing modulators are actively being developed for controlling bacterial biofilm, and this approach appears to be more effective for gram-positive bacteria [69][70][71]. Two types of anti-QS chemicals are particularly promising, namely phytochemicals and plant by-products [72].…”

Section: Block Quorum Sensing Signalingmentioning

confidence: 99%

Mechanisms and Control Strategies of Antibiotic Resistance in Pathological Biofilms

Ying¹,

Yang²,

Zhang³

et al. 2021

J. Microbiol. Biotechnol.

View full text Add to dashboard Cite

Biofilms are protected microbial structures enclosed by a self-secreted extracellular matrix [1]. Bacteria biofilm is one of the most successful forms of life, being widely distributed in a diversity of environments [2]. All higher organisms (including humans) are colonized by microorganisms that form biofilms, mostly bacteria [3]. The ability of biofilms to escape the host immune system and resist antibiotics poses great health threats to patients [4,5].Biofilm formation contributes to drug resistance and inflammation, causing persistent infections in patients [6]. Biofilms also function as cell reservoirs that can repopulate infection sites after the release of suppression. For example, biofilm formation is a major concern for cystic fibrosis pneumonia caused by Pseudomonas aeruginosa and urinary tract infections caused by Escherichia coli, both of which are refractory to multiple antibiotics [7]. Therefore, basic research on biofilm formation and the mechanism of their resistance is of great clinical relevance. The objective of this review is to summarize the current research progress in antibiotic resistance mechanisms associated with bacterial biofilms and anti-biofilm strategies, which may greatly benefit patients who suffer from biofilm-related infections. Bacterial Biofilms Structure and Characteristics of Bacterial BiofilmThe physical scaffold of a biofilm is the matrix of extracellular polymeric substances (EPSs), self-secreted substances that keep bacterial cells in a contained structure and attach them to surfaces [8]. Most of the biomass of the biofilm is hydrated EPS rather than bacterial cells, which only make up between 2% to 15% of the total biofilm mass [9]. EPS is mostly composed of polysaccharides, proteins, lipids and extracellular DNA (eDNA) (Fig. 1) [9]. Enhanced antimicrobial resistance, nutrient capture and social cooperation are three main characteristic features of biofilms, and the EPS matrix underlies these important properties [2]. The structures of biofilms somewhat resembles tissues of higher organisms, which are structurally complex and highly heterogenous in gene expression [10], both contributing to the resistance mechanisms of biofilm. Life Cycle of Bacterial BiofilmsThe transition from planktonic growth to biofilm is a complex and highly regulated process that follows a few steps (Fig. 1). The first step is the initial attachment of planktic bacterial cells to a surface, which often happens when cells are under environmental stress. The propelling structures, such as appendages, fimbriae and sex pili, Bacterial biofilm is a community of bacteria that are embedded and structured in a self-secreted extracellular matrix. An important clinical-related characteristic of bacterial biofilms is that they are much more resistant to antimicrobial agents than the planktonic cells (up to 1,000 times), which is one of the main causes of antibiotic resistance in clinics. Therefore, infections caused by biofilms are notoriously difficult to eradicate, such as lung infection caused by Pseudom...

show abstract

“…[56] Work from our lab has focused on an in-depth analysis of the structural and functional properties of the S. pneumoniae CSPs through systematic evaluation of each residue in order to determine their importance and uncover potent CSP-based QS-modulators. [59] A study from Yang et al generated a wide range of peptides derived from Ala and D-enantiomer scanning of the CSP1 signal to determine each residue's contribution to ComD receptor recognition, binding, and activation. [60] A follow-up study has focused on the N-terminal role of CSP1 in receptor recognition and activation, and a thorough investigation was carried out at the Glu1 position by introducing amino acids (AAs) with different side-chain length, polarity, and F I G U R E 1 Schematic representation of S. pneumoniae competence regulon quorum sensing (QS) circuit and inhibitory hot spots.…”

Section: Competence Vs Virulence In S Pneumoniaementioning

confidence: 99%

Strategies to attenuate the competence regulon in Streptococcus pneumoniae

Lella

Tal‐Gan

2021

Peptide Science

Self Cite

View full text Add to dashboard Cite

Streptococcus pneumoniae is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Natural competence for genetic transformation in S. pneumoniae plays an important role in aiding pathogenicity and it is the bestcharacterized feature to acquire antimicrobial resistance genes by a frequent process of recombination. In S. pneumoniae, competence, along with virulence factor production, is controlled by a cell-density communication mechanism termed the competence regulon. In this review, we present the recent advances in the development of alternative methods to attenuate the pathogenicity of S. pneumoniae by targeting the various stages of the non-essential competence regulon communication system. We mainly focus on new developments related to competitively intercepting the competence regulon signaling through the introduction of promising dominant-negative Competence Stimulating Peptide (CSP) scaffolds. We also discuss recent reports on antibiotics that can block CSP export by disturbing the proton motive force across the membrane and various ways to control the pneumococcal pathogenicity by activating the counter signaling circuit and targeting the pneumococcal proteome.

show abstract

Development and utilization of peptide-based quorum sensing modulators in Gram-positive bacteria

Abstract: Quorum sensing (QS) is a mechanism by which bacteria regulate cell density-dependent group behaviors. Gram-positive bacteria generally rely on auto-inducing peptide (AIP)-based QS signaling to regulate their group behaviors. To...

Cited by 37 publications

References 75 publications

Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides

Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides

Mechanisms and Control Strategies of Antibiotic Resistance in Pathological Biofilms

Strategies to attenuate the competence regulon in Streptococcus pneumoniae

Contact Info

Product

Resources

About