Biology subjects

Goemans, C. V.

Publications and source records attributed to Goemans, C. V..

3 recordsLinked to original sources

bioRxiv2026

Bacteriostatic antibiotics drive bacterial death by reshaping competitive interactions

Protein synthesis inhibitors, including macrolides and tetracyclines, are classically defined as bacteriostatic because they arrest bacterial growth without directly causing death. Yet their effects vary widely across bacterial species and communities, suggesting that additional mechanisms shape their ecological impact. Here we show that the human gut commensal Escherichia coli ED1a kills the laboratory strain BW25113 specifically when protein synthesis is inhibited. We find that this killing is mediated by colicin K, a bacteriocin encoded on a plasmid carried by ED1a alongside its cognate immunity factor. Because ED1a itself is far more sensitive to protein synthesis inhibitors than BW25113 (surviving antibiotic exposure roughly 1,000-fold less efficiently), we expected antibiotic treatment to favour BW25113 in co-culture. Instead, we found that antibiotic exposure suppresses BW25113 below the population density required to coexist with colicin-producing ED1a, triggering colicin-dependent elimination of the sensitive strain, ultimately leading to the collapse of both populations. Screening a library of 1,085 E. coli isolates revealed that this antibiotic-induced, toxin-mediated killing is not unique to the ED1a-BW25113 pair but is a widely conserved interaction across natural strain combinations. Thus, a nominally bacteriostatic antibiotic can indirectly drive bacterial death by reshaping competitive dynamics between strains rather than by any direct bactericidal action. These findings reveal a previously unrecognized route by which protein synthesis inhibitors influence bacterial competition, and offer a framework for understanding how clinically important bacteriostatic antibiotics can eliminate bacterial populations and restructure microbial communities.

microbiology↗

bioRxiv2022

A molecular plugin rescues GroEL/ES substrates from pre-folding oxidation

Hsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these chaperonins promote folding remain unsolved. Here, we report that the bacterial Hsp60 chaperonin GroEL forms a stable, functionally relevant complex with the chaperedoxin CnoX, a protein combining a chaperone and a redox function. Binding of GroES (Hsp10) to GroEL induces CnoX release. Cryo-electron microscopy provided crucial structural information on the GroEL-CnoX complex, showing that CnoX binds GroEL outside the substrate-binding site via a highly conserved C-terminal -helix. Furthermore, the identification of complexes in which CnoX, bound to GroEL, forms mixed-disulfides with GroEL substrates indicates that CnoX likely functions as a redox quality-control plugin for GroEL. Proteins sharing structural features with CnoX exist in eukaryotes, which suggests that Hsp60 molecular plugins have been conserved through evolution.

biochemistry↗

bioRxiv2020

Dissecting the collateral damage of antibiotics on gut microbes

Antibiotics are used for fighting pathogens, but also target our commensal bacteria as a side effect, disturbing the gut microbiota composition and causing dysbiosis and disease1-3. Despite this well-known collateral damage, the activity spectrum of the different antibiotic classes on gut bacteria remains poorly characterized. Having monitored the activities of >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome4, we here characterize further the 144 antibiotics therein, representing all major classes. We determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic profiling to 10 additional species to validate these results and link to available data on antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, including generation-dependent effects by quinolones and phylogeny-independence by {beta}-lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein synthesis inhibitors, inhibited almost all commensals tested. We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals5-8 and humans9-11. To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria12 and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species. By screening >1,000 drugs, we identified several such antidotes capable of protecting gut species from these antibiotics without compromising their activity against relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on gut commensals, uncovers a previously unappreciated and broad bactericidal effect of prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the collateral damage caused by antibiotics on human gut commensals.

microbiology↗