De Vliegher, S. | Search bioRxiv

bioRxiv2025

Mapping of Quorum Sensing Landscape of Commensal and Pathogenic Staphylococci Reveals a Largely Inhibitory Interaction Network

Staphylococci utilize secreted autoinducing peptides (AIPs) to regulate group behaviour through a process called quorum sensing (QS). For staphylococcal pathogens such as S. aureus, QS regulates expression of major virulence factors and QS inhibition has been proposed as an alternative to antibiotics for treatment of infections with methicillin resistant S. aureus (MRSA). Here, we surveyed the interaction map between QS systems of the pathogens Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis and the 36 currently known AIPs from 22 staphylococcal species. We identified seven of these ribosomally synthesized and post-translationally modified peptides (RiPPs) in this study and all synthetic peptides were assessed for their ability to modulate QS. The mapped interactions of >280 native QS pairings were divided into human- and animal-associated staphylococci showing substantial differences in inhibitory potencies between the groups. In particular, AIPs of the bovine-associated species S. simulans displayed potential as QS inhibitors in the strains investigated in this study and were therefore chosen as starting point for a structure-activity relationship study. This study provides insights into the requirements for QS interference, yielding the most potent inhibitors reported to date for S. epidermidis and S. lugdunensis. Further, we tested an S. simulans AIP as anti-virulence agent in an assay to assess risk of acquired suppression of the inhibitory effect, and we established an assay set-up to successfully monitor agr deactivation of virulent MRSA by the QS inhibitor. Finally, a peptide was shown to attenuate skin infection caused by MRSA in a mouse model. Our results reveal a complex network of staphylococcal interactions and provide further impetus for the development of therapeutic strategies, based on QS modulation to target antibiotic-resistant pathogens. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/635662v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@f2be0aorg.highwire.dtl.DTLVardef@9aa0c2org.highwire.dtl.DTLVardef@1b02c26org.highwire.dtl.DTLVardef@12273a7_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

Characterization of genetic diversity and population structure within Staphylococcus chromogenes by multilocus sequence Typing

Staphylococcus chromogenes is a common skin commensal in cattle and has been identified as a frequent cause of bovine mastitis and intramammary infections. To better understand the extent of strain diversity within this species and to facilitate study of strain variation as a factor in pathogenicity, we have developed a seven locus Multilocus Sequence Typing (MLST) scheme. The scheme was tested on 120 isolates collected from three geographic locations, Vermont and Washington State in the United States and Belgium. A total of 46 sequence types (STs) were identified with most of the STs being location specific. The utility of the typing scheme is indicated by a discrimination power of 95.6% for all isolates and greater than 90% for isolates from each of the three locations. Phylogenetic analysis placed 39 of the 46 STs into single core group consistent with a common genetic lineage; the STs in this group differ by less than 0.5% at the nucleotide sequence level. Most of the diversification in this lineage group can be attributed to mutation; recombination plays a limited role. This lineage group includes two clusters of single nucleotide variants in starburst configurations indicative of recent clonal expansion; nearly 50% of the isolates sampled in this study are in these two clusters. The remaining seven STs were set apart from the core group by having alleles with highly variable sequences at one or more loci. Recombination had a higher impact than mutation in the diversification of these outlier STs. Alleles with hypervariable sequences were detected at five of the seven loci used in the MLST scheme; the average sequence distances between the hypervariable alleles and the common core alleles ranged from 12 to 34 nucleotides. The extent of these sequence differences suggests the hypervariable alleles may be remnants of an ancestral genotype.

microbiology↗