About

Microbes are capable of thriving in most extreme conditions, including high temperature, acidity, high pressure, radiation, dessication, or poisonous environments. We focus on the molecular mechanisms and determinants that allow for their extreme adaptability.

Research topics

• Chemistry
• Microbiology
• Genetics
• Biology
• Biochemistry
• Cell biology
• Computational biology

Selected publications

• Correction to: Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes

  Environmental Science and Pollution Research · 2026-04-09

  articleOpen access
  PublisherOA PDFDOI

• A Novel Screening System to Characterize and Engineer Quorum Quenching Lactonases

  Biotechnology and Bioengineering · 2025-01-17 · 1 citations

  articleOpen accessSenior authorCorresponding

  N-acyl l-homoserine lactones are signaling molecules used by numerous bacteria in quorum sensing. Some bacteria encode lactonases, which can inactivate these signals. Lactonases were reported to inhibit quorum sensing-dependent phenotypes, including virulence and biofilm. As bacterial signaling is dependent on the type of molecule used, lactonases with high substrate specificity are desirable for selectively targeting species in communities. Lactonases characterized from nature show limited diversity in substrate preference, making their engineering appealing but complicated by the lack of convenient assays for evaluating lactonase activity. We present a medium-throughput lactonase screening system compatible with lysates that couples the ring opening of N-acyl l-homocysteine thiolactones with 5,5-dithio-bis-(2-nitrobenzoic acid) to generate a chromogenic signal. We show that this system is applicable to lactonases from diverse protein families and demonstrate its utility by screening mutant libraries of GcL lactonase from Parageobacillus caldoxylosilyticus. Kinetic characterization corroborated the screening results with thiolactonase and homoserine lactonase activity levels. This system identified GcL variants with altered specificity: up to 1900-fold lower activity for long-chain N-acyl l-homoserine lactone substrates and ~38-fold increase in preference for short-chain substrates. Overall, this new system substantially improves the evaluation of lactonase activity and will facilitate the identification and engineering of quorum quenching enzymes.

  PublisherOA PDFDOI

• α<i>‐N</i>‐Methyltransferase regiospecificity is mediated by proximal, redundant enzyme–substrate interactions

  Protein Science · 2025-01-22 · 1 citations

  articleOpen accessCorresponding

  N-Methylation of the peptide backbone confers pharmacologically beneficial characteristics to peptides that include greater membrane permeability and resistance to proteolytic degradation. The borosin family of ribosomally synthesized and post-translationally modified peptides offer a post-translational route to install amide backbone α-N-methylations. Previous work has elucidated the substrate scope and engineering potential of two examples of type I borosins, which feature autocatalytic precursors that encode N-methyltransferases that methylate their own C-termini in trans. We recently reported the first discrete N-methyltransferase and precursor peptide from Shewanella oneidensis MR-1, a minimally iterative, type IV borosin that allowed the first detailed kinetic analyses of borosin N-methyltransferases. Herein, we characterize the substrate scope and resilient regiospecificity of this discrete N-methyltransferase by comparison of relative rates and methylation patterns of over 40 precursor peptide variants along with structure analyses of nine enzyme-substrate complexes. Sequences critical to methylation are identified and demonstrated in assaying minimal peptide substrates and non-native peptide sequences for assessment of secondary structure requirements and engineering potential. This work grants understanding towards the mechanism of substrate recognition and iterative activity by discrete borosin N-methyltransferases.

  PublisherOA PDFDOI

• N-acyl homoserine lactone signaling modulates bacterial community associated with human dental plaque

  npj Biofilms and Microbiomes · 2025-11-17 · 1 citations

  articleOpen accessSenior author

  Dental plaque is a complex oral biofilm responsible for periodontal diseases. Bacterial biofilms are often regulated by Quorum Sensing (QS) mediated by N-acyl homoserine lactones (AHLs). While their presence and roles in oral microbiota have been debated, emerging evidence suggests AHLs influence oral biofilm development. AHLs are detectable in a microbial community derived from human dental plaque cultured under 5% CO2 but not under anaerobic conditions. Manipulating QS in this community via AHL lactonases enriched commensals and pioneer colonizers under 5% CO₂, whereas in anaerobic conditions exogenous AHLs promoted late colonizers. QS disruption reduced biofilm formation, enhanced sucrose fermentation to lactate, and altered metabolic profiles of the community depending on the lactonase substrate specificity. Our findings highlight the importance of AHL-mediated QS in oral biofilm development and suggest its differential roles under aerobic versus anaerobic conditions. Targeting QS may offer a novel strategy for managing oral biofilms and preventing periodontal disease.

  PublisherOA PDFDOI

• Correction: Targeting quorum sensing for manipulation of commensal microbiota

  BMC Biotechnology · 2025-01-31 · 1 citations

  erratumOpen access
  PublisherOA PDFDOI

• Durable formulations of quorum quenching enzymes

  Scientific Reports · 2025-07-28 · 1 citations

  articleOpen accessSenior author

  Enzymes with industrial potential often face limitations due to stability and longevity constraints. Thermostable quorum quenching lactonases are appealing biotechnology tools for controlling microbial pathogenicity and biofilm formation via the interference of quorum sensing. However, the effective formulation of these enzymes remains a challenge. Here, we evaluate the resistance and activity of two thermostable quorum quenching lactonase enzymes (SsoPox and GcL) across diverse formulations relevant to industrial applications. We systematically tested these enzymes with 16 different crop adjuvants (including oils, an anti-foaming agent, surfactants, deposition aids, a water conditioner, and a sticking agent) over a 210-day period, demonstrating broad compatibility except with oil-based adjuvants. Additionally, both enzymes maintained their activity when incorporated into five different coating bases (acrylic, silicone, polyurethane, epoxy, and latex) with activity levels varying according to polymer type. Further investigation of enzymatic acrylic coating characterized the effects of salt water and temperature on enzyme activity levels. Functionalized coatings maintained remarkable stability over 250 days in both wet and dry conditions. These findings establish a practical demonstration and framework for integrating quorum quenching lactonases into industrial materials and formulations, significantly advancing their potential for 'real-world' applications for microbial control across multiple sectors.

  PublisherOA PDFDOI

• Quorum quenching enzymes disrupt bacterial communication in a sex‐ and dose‐dependent manner

  Animal Models and Experimental Medicine · 2025-02-13 · 1 citations

  articleOpen access

  BACKGROUND: Over the past 50 years, the incidence of obesity has gradually increased, necessitating investigation into the multifactorial contributors to this disease, including the gut microbiota. Bacteria within the human gut microbiome communicate using a density-dependent process known as quorum sensing (QS), in which autoinducer (AI) molecules (e.g., N-acyl-homoserine lactones [AHLs]) are produced to enable bacterial interactions and regulate gene expression. METHODS: We aimed to disrupt QS using quorum quenching (QQ) lactonases GcL and SsoPox, which cleave AHL signaling molecules in a taxa-specific manner based on differing enzyme affinities for different substrates. We hypothesized that QQ hinders signals from obesity-associated pathobionts, thereby slowing or preventing obesity. RESULTS: In a murine model of diet-induced obesity, we observed GcL and SsoPox treatments have separate sex-dependent and dose-dependent effects on intestinal community composition and diversity. Notably, male mice given 2 mg/mL SsoPox exhibited significant changes in the relative abundances of gram-negative taxa, including Porphyromonadaceae, Akkermansiaceae, Muribaculaceae, and Bacteroidales (Kruskal-Wallis p < 0.001). Additionally, we used covariance matrix network analysis to model bacterial taxa co-occurrence due to QQ enzyme administration. There were more associations among taxa in control mice, particularly among gram-negative bacteria, whereas mice receiving SsoPox had the fewest associations. CONCLUSIONS: Overall, our study establishes proof of concept that QQ is a targetable strategy for microbial control in vivo. Further characterization and dosage optimization of QQ enzymes are necessary to harness their therapeutic capability for the treatment of chronic microbial-associated diseases.

  PublisherOA PDFDOI

• NIH’s 15% cap: a cost comparison and research outlook

  EMBO Reports · 2025-03-18 · 2 citations

  articleOpen accessSenior author

  The decision by the US government to cap the NIH grant overhead rate to 15% will likely underfund the country’s research institutions for their infrastructure relative to their international peers and the private sector. This move could jeopardize the country’s lead in the biological sciences.

  PublisherOA PDFDOI

• Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer

  Cancer Medicine · 2025-06-01 · 1 citations

  articleOpen access

  BACKGROUND: The gut microbiota is associated with colorectal cancer (CRC) risk and CRC metastatic potential. However, the role of bacteria in CRC progression and metastasis remains unclear. AIMS: Here, we hypothesized that microbial communication, mediated through quorum sensing (QS), was a critical component regulating microbial functions related to cancer progression and metastasis. MATERIALS & METHODS: To test this, male and female C57BL/6 mice were injected with organoids modeling aggressive colon cancer (CRC), carrying mutations in Apc, Kras, p53, and Smad4. Two groups of mice were treated with two different quorum quenching (QQ) lactonases (GcL or SsoPox) for 8 weeks (n = 10/group/sex). Fecal samples were collected weekly and characterized by Illumina next-generation sequencing, with tissues collected during necropsy. RESULTS: = 2.554, p = 0.110), and every female, SsoPox-treated mouse that developed a primary tumor also developed metastasis by the experimental endpoint. However, QQ treatment was shown to minimally affect the gut microbiome composition. Similarly, no significant differences were observed in inflammatory response as assessed by immunofluorescent staining or fecal concentrations of immunoglobulin A, calprotectin, or lipocalin-2. Differences in fecal short-chain fatty acid concentrations also did not differ significantly. DISCUSSION: These results suggest that QQ treatment has a sex-based effect on CRC metastatic rate. CONCLUSION: Targeting communication among the gut microbiome may be a promising avenue for the development of CRC therapies that minimally impact microbial community composition and host immune response.

  PublisherOA PDFDOI

• Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching Lactonases

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-01

  preprintOpen accessCorresponding

  Abstract Several enzymes from the metallo-β-lactamase-like family of lactonases (MLLs) degrade N- acyl-L-homoserine lactones (AHLs). In doing so, they play a role in a microbial communication system, quorum sensing, which contributes to pathogenicity and biofilm formation. There is currently great interest in designing quorum quenching ( QQ ) enzymes that can interfere with this communication and be used in a range of industrial and biomedical applications. However, tailoring these enzymes for specific targets requires a thorough understanding of their mechanisms and the physicochemical properties that determine their substrate specificities. We present here a detailed biochemical, computational, and structural study of the MLL GcL, which is highly proficient, thermostable, and has broad substrate specificity. Strikingly, we show that GcL does not only accept a broad range of substrates but is also capable of utilizing different reaction mechanisms that are differentially used in function of the substrate structure or the remodeling of the active site via mutations. Comparison of GcL to other lactonases such as AiiA and AaL demonstrates similar mechanistic promiscuity, suggesting this is a shared feature across lactonases in this enzyme family. Mechanistic promiscuity has previously been observed in the lactonase/paraoxonase PON1, as well as with protein tyrosine phosphatases that operate via a dual general-acid mechanism. The apparent prevalence of this phenomenon is significant from both a biochemical and an engineering perspective: in addition to optimizing for specific substrates, it is possible to optimize for specific mechanisms, opening new doors not just for the design of novel quorum quenching enzymes, but also of other mechanistically promiscuous enzymes.

  PublisherDOI

Recent grants

• Cracking the Microbial Language: Characterization of Novel Biocatalysts for Interfering with Signaling to Illuminate Quorum Sensing Mechanisms

  NIH · $2.3M · 2019–2030

Frequent coauthors

• Éric Chabrière

  Aix-Marseille Université

  272 shared

• C. Lecomte

  63 shared

• Giuseppe Manco

  Institute of Protein Biochemistry

  61 shared

• S. Moniot

  Merck (Germany)

  60 shared

• Céline Bergonzi

  Biotechnology Institute

  54 shared

• S. Moniot

  Institut de Biologie Structurale

  49 shared

• E. Chabriere

  Université de Lorraine

  49 shared

• Patrick Masson

  Institut de Physique et Chimie des Matériaux de Strasbourg

  49 shared

Labs

• Elias LabPI

Awards & honors

• Dean's Distinguished Research Lectureship
• Dean's Tribute to Excellence in Research
• Dean’s Tribute to Excellence in Education
• Herz Faculty Teaching Development Awards
• Dr. James E. Rubin Medical Memorial Award