Publications

Zoja Germuskova, Eleonora Pronzini, Fanny Wegner, Tim Roloff, T. Song, M. Barancekova, A.Cizek, Michael Addidle, Murray Robinson, Marc Dieu, Chaitanya Tellapragada, Christian G Giske, Kirstine Kobberøe Søgaard, Els M Broens, Francesco RenzI, Adrian Egli
Eur J Clin Microbiol Infect Dis

Background: Capnocytophaga canimorsus (C. canimorsus) is a zoonotic pathogen transmitted by dogs and cats that can cause severe infections in humans. Antimicrobial susceptibility data remain limited, but increasing genomic evidence suggests that functional β-lactamase genes may be more widespread than previously recognized.

Methods: Three C. canimorsus isolates harboring class D β-lactamase genes were selected by genomic screening from a larger collection of the Global Capnocytophaga Consortium for detailed characterization: two isolates from human clinical infections from Sweden and New Zealand, and a commensal canine isolate from the Czech Republic. We used hybrid Illumina-Nanopore genome assemblies, phylogenetic analysis, and structural modeling to characterize the genomic context and the predicted protein features of the β-lactamase genes. The functional impact of the β-lactamases on antibiotic activity was assessed by minimum inhibitory concentration (MIC) testing and confirmed through recombinant expression in the β-lactamase-negative reference strain C. canimorsus 5 (Cc5).

Results: We detected blaOXA-347 in a canine isolate and, for the first time, in a clinical C. canimorsus isolate from human infection. Additionally, we identified a previously uncharacterized allele, newly designated blaOXA-1422, in another clinical isolate. Both β-lactamases were chromosomally encoded without clear mobile genetic elements and were part of a distinct phylogenetic cluster within the OXA family. Structural modeling showed conserved class D β-lactamase architecture. Strains carrying either gene had elevated MICs for multiple β-lactams, and expression of each gene in Cc5 recapitulated these effects.

Conclusions: The identification and phenotypic characterization of OXA-type β-lactamases in clinical C. canimorsus isolates refine our understanding of β-lactamase diversity in this species and underscore the need for systematic investigations of β‑lactamase prevalence in this zoonotic pathogen.

Giusy Castagliuolo, Eugenio Notomista, Alessia Sordillo, Laura Barone, Dario Antonini, Francesco Renzi, Anna Zanfardino and Mario Varcamonti
antibiotics

The increasing problem of antibiotic resistance is a critical global health issue, necessi‑
tating the development of alternative therapeutic strategies to manage infections effec‑
tively. Among the promising solutions are human antimicrobial peptides (AMPs), natu‑
rally occurring molecules known for their broad spectrum of antimicrobial activity. Back‑
ground/Objectives: This study investigates the potential of some AMPs, selected through
a bioinformatic approach, as alternatives to conventional antibiotics, particularly focusing
on their efficacy against species within the Bacteroidota phylum. These species, including
pathogens such as Porphyromonas gingivalis, Capnocytophaga ochracea, and Capnocytophaga
canimorsus, are well known for their roles in various human infections and related diseases.
Non‑pathogenic environmental species, such as Flavobacterium johnsoniae, are also included
in this group, frequently used as a model organism. Methods: By analyzing the antimi‑
crobial efficacy, mechanisms of action, and potential therapeutic applications of human
AMPs, this research underscores their significance in addressing the challenge of antibi‑
otic resistance. Results: This study identified three peptides, KTL24, LIR23, and MFP22, as
particularly interesting. These peptides are derived from specific human proteins, namely
SPI1, NAPSA and SCUB1. Conclusions: Their notable antimicrobial potential suggests
that AMPs could serve either as a complementary treatment alongside traditional antibi‑
otics or as a standalone therapy, mitigating the ongoing spread of antibiotic resistance and
offering an alternative in global health strategies

Tom De Smet, Elisabeth Baland, Fabio Giovannercole, Julien Mignon, Laura Lizen, Rémy Dugauquier, Frédéric Lauber, Marc Dieu, Gipsi Lima-Mendez, Catherine Michaux, Damien Devos & Francesco Renzi
06 March 2025

Lipoproteins are key outer membrane (OM) components in Gram-negative bacteria, essential for functions like membrane biogenesis and virulence. Bacteroidota, a diverse and widespread phylum, produce numerous OM lipoproteins that play vital roles in nutrient acquisition, Type IX secretion system (T9SS), and gliding motility. In Escherichia coli, lipoprotein transport to the OM is mediated by the Lol system, where LolA shuttles lipoproteins to LolB, which anchors them in the OM. However, LolB homologs were previously thought to be limited to γ- and β-proteobacteria. This study uncovers the presence of LolB in Bacteroidota and demonstrates that multiple LolA and LolB proteins co-exist in various species. Specifically, in Flavobacterium johnsoniae, LolA1 and LolB1 transport gliding motility and T9SS lipoproteins to the OM. Notably, these proteins are not interchangeable with their E. coli counterparts, indicating functional specialization. Some lipoproteins still localize to the OM in the absence of LolA and LolB, suggesting the existence of alternative transport pathways in Bacteroidota. This points to a more complex lipoprotein transport system in Bacteroidota compared to other Gram-negative bacteria. These findings reveal previously unrecognized lipoprotein transport mechanisms in Bacteroidota and suggest that this phylum has evolved unique strategies to manage the essential task of lipoprotein localization.

Fabio Giovannercole, Tom de Smet, Miguel Angel Vences-Guzmán, Frédéric Lauber, Rémy Dugauquier, Marc Dieu, Laura Lizen, Jonas Dehairs, Gipsi Lima-Mendez, Ziqiang Guan, Christian Sohlenkamp, Francesco Renzi
3 March 2025
In Proteobacteria, the outer membrane protein TamA and the inner membrane-anchored protein TamB form the Translocation and Assembly Module (TAM) complex, which facilitates the transport of autotransporters, virulence factors, and likely lipids across the two membranes. In Bacteroidota, TamA is replaced by TamL, a TamA-like lipoprotein with a lipid modification at its N-terminus that likely anchors it to the outer membrane. This structural difference suggests that TamL may have a distinct function compared to TamA. However, the role of TAM in bacterial phyla other than Proteobacteria remains unexplored.
Our study aimed to elucidate the function of TamL in Flavobacterium johnsoniae, an environmental Bacteroidota. Unlike its homologues in Proteobacteria, we found that TamL and TamB are essential in F. johnsoniae. Through genetic, phenotypic, proteomic, and lipidomic analyses, we show that TamL depletion severely compromises outer membrane integrity, as evidenced by reduced cell viability, altered cell shape, increased susceptibility to membrane-disrupting agents, and elevated levels of outer membrane lipoproteins. Notably, we did not observe an overall decrease in the levels of β-barrel outer membrane proteins, nor substantial alterations in outer membrane lipid composition.
By pull-down assays, we found TamL co-purifying with TamB in F. johnsoniae, suggesting an interaction. Furthermore, we found that while TamL and TamB monocistronic genes are conserved among Bacteroidota, only some species encode multiple TamL, TamB and TamA proteins.
To our knowledge, this study is the first to provide functional insights into a TAM subunit beyond Proteobacteria.
Fernández Vecilla, D, López, IA, Muro, FEC, Vivanco, CA, Renzi, F, Martínez, MEP, Soria, JR & Del Arco, JL
Revista espanola de quimioterapia, vol. 26, no. 1, pp. 92-96. https://doi.org/10.37201/req/060.2022
Fernandez Vecilla, D, Aspichueta Vivanco, C, Angulo Lopez, I, Baraia-Etxaburu Artetxe, J M, Renzi, F, Diaz de Tuesta del Arco, J L
Access Microbiology, vol 4, issue 6, https://doi.org/10.1099/acmi.0.000368
Fernandez Vecilla, D, Ugalde Zarraga, E, Urrutikoechea-Gutierrez, M J, Renzi, F, Diaz de Tuesta del Arco, J L
Access Microbiology, vol 4, issue 5, https://doi.org/10.1099/acmi.0.000352
Fabian Stefan Franz Hartmann, Mélanie Grégoire, Francesco Renzi and Frank Delvigne
Trends in Biotechnology 2024
Viviane Donner, Marta Buzzi, Vladimir Lazarevic, Nadia Gaïa, Myriam Girard, Francesco Renzi, Gesuele Renzi, Abdessalam Cherkaoui, Jacques Schrenzel
European Journal of Clinical Microbiology & Infectious Diseases volume 39, pages1993–1995(2020)
Estelle Hess, Francesco Renzi, Panu Karhunen, Mélanie Dol, Adrien Lefèvre, Jenni Antikainen, Elodie Carlier, Johanna Hästbacka, and Guy R. Cornelis
Emerging Infectious Diseases
Francesco Renzi, Estelle Hess, Melanie Dol, Dunia Koudad, Elodie Carlier, Maria Ohlén, Edward Moore & Guy Richard Cornelis
Emerging Microbes & Infections
Hack, K, Renzi, F, Hess, E, Lauber, F, Douxfils, J, Dogné, JM & Cornelis, GR
Journal of thrombosis and haemostasis : JTH. DOI: 10.1111/jth.13605
Renzi. F, Ittig S. J., Sadovskaya I., Hess E., Lauber F., Dol M., Shin H., Mally M., Fiechter C., Sauder U., Chami M., Cornelis G. R.
Scientific Reports 2016 Dec 15;6:38914. doi: 10.1038/srep38914.
Shin H., Mally M., Kuhn M., Paroz C., Cornelis G.R
2007

J Infect Dis. 2007 Feb 1;195(3):375-86. Epub 2006 Dec 19.

Mally M., Cornelis G.R
2008

Appl Environ Microbiol. 2008 Oct;74(20):6369-77. doi: 10.1128/AEM.01218-08. Epub 2008 Aug 22.

Mally M., Shin H., Paroz C., Landmann R., Cornelis G.R
2008

PloS Pathog. 2008 Sep 26;4(9):e1000164. doi: 10.1371/journal.ppat.1000164.

Meyer S., Shin H., Cornelis G.R
2008

Immunobiology. 2008;213(9-10):805-14. doi: 10.1016/j.imbio.2008.07.019. Epub 2008 Sep 7.

Mally M., Paroz C., Shin H, Meyer S., Soussoula L.V., Schmiediger U., Saillen-Paroz C., Cornelis GR
2009

Microbes Infect. 2009 Apr;11(4):509-14. doi: 10.1016/j.micinf.2009.02.005. Epub 2009 Mar 11.

Shin H., Mally M., Meyer S., Fiechter C., Paroz C., Zähringer U., Cornelis G.R
2009

Infect Immun. 2009 Jun;77(6):2262-71. doi: 10.1128/IAI.01324-08. Epub 2009 Mar 23

Renzi F., Manfredi P., Mally M., Moes S., Jenö P., Cornelis G.R
2011

PLoS Pathog. 2011 Jun;7(6):e1002118.

Manfredi P., Renzi F., Mally M., Sauteur L., Schmaler M., Moes S., Jenö P., Cornelis G.R
2011

Mol Microbiol. 2011 Aug;81(4):1050-60. doi: 10.1111/j.1365-2958.2011.07750.x.

Manfredi P., Pagni M., Cornelis G.R
2011

J Bacteriol. 2011 Oct;193(19):5558-9. doi: 10.1128/JB.05853-11

Manfredi P., Pagni M., Cornelis G.R
2011

J Bacteriol. 2011 Oct;193(19):5558-9. doi: 10.1128/JB.05853-11

Manfredi P., Pagni M., Cornelis G.R
2011

J Bacteriol. 2011 Oct;193(19):5558-9. doi: 10.1128/JB.05853-11

Ittig S., Lindner B., Stenta M., Manfredi P., Zdorovenko E., Knirel Y.A., dal Peraro M., Cornelis G.R., Zähringer U
2012

PLoS Pathog. 2012;8(5):e1002667. doi: 10.1371/journal.ppat.1002667. Epub 2012 May 3.

Zähringer U., Ittig S., Lindner B., Moll H., Schombel U., Gisch N., Cornelis G.R
2014

J Biol Chem. 2014 Aug 22;289(34):23963-76. doi: 10.1074/jbc.M114.571489. Epub 2014 Jul 2.

Manfredi P., Lauber F., Renzi F., Hack K., Hess E. & Cornelis, G.R
20014

Infection and Immunity. 83, 1, p. 300-310 11 p.

Manfredi P., Lauber F., Renzi F., Hack K., Hess E. & Cornelis, G.R
20014

Infection and Immunity. 83, 1, p. 300-310 11 p.

Manfredi P., Renzi F., Cornelis G.R
2015

Genome Announc. 2015 May 28;3(3). pii: e00193-15. doi: 10.1128/genomeA.00193-15.

Manfredi P., Renzi F., Cornelis G.R.
2015

Genome Announc. 2015 May 28;3(3). pii: e00199-15. doi: 10.1128/genomeA.00199-15.

Manfredi P., Renzi F., Cornelis G.R
2015

Genome Announc. 2015 May 28;3(3). pii: e00200-15. doi: 10.1128/genomeA.00200-15.

Manfredi P., Renzi F., Cornelis G.R
2015

Genome Announc. 2015 May 28;3(3). pii: e00200-15. doi: 10.1128/genomeA.00200-15.

Renzi F., Manfredi P., Dol M., Fu J., Vincent S., Cornelis G.R
2015

MBio. 2015 Mar 3;6(2):e02507. doi: 10.1128/mBio.02507-14.

Renzi F., Dol M., Raymackers A., Manfredi P., Cornelis G.R
2015

Emerg Microbes Infect. 2015 Aug;4(8):e48. doi: 10.1038/emi.2015.48. Epub 2015 Aug 19.

Magnette A., Huang T.D., Renzi F., Bogaerts P., Cornelis G.R., Glupczynski Y
2016

Diagn Microbiol Infect Dis. 2016 Jan;84(1):12-5. doi: 10.1016/j.diagmicrobio.2015.09.016. Epub 2015 Sep 30.

Renzi F., Zähringer U., Chandler C.E., Ernst R.K., Cornelis G.R., Ittig S.J
2015

Infection and Immunity. 2015 Dec 7. pii: IAI.01006-15.

Renzi F., Zähringer U., Chandler C.E., Ernst R.K., Cornelis G.R., Ittig S.J
2015

Infection and Immunity. 2015 Dec 7. pii: IAI.01006-15.

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