Samuel Garcia Huete

@irycis.org

Department of Infectious Diseases
Ramón y Cajal Health Research Institute (IRYCIS)

Samuel Garcia Huete


                        Download Compact PDF  
https://researchid.co/sgarciah
Molecular microbiology is my expertise, microbial evolution is my passion, and helping others is my driving force. Infectious diseases are still a global challenge that needs a holistic approach, my humble efforts aim to contribute to the fight.

"Messieurs, c'est les microbes qui auront le dernier mot" (Louis Pasteur)

EDUCATION

PhD in Microbiology, Institut Pasteur & Université Paris Cité
MScR Infection and Immunity, University of Edinburgh & Roslin Institute

RESEARCH, TEACHING, or OTHER INTERESTS

Microbiology, Infectious Diseases, Ecology, Evolution, Behavior and Systematics, Molecular Biology
9

Scopus Publications

179

Scholar Citations

7

Scholar h-index

3

Scholar i10-index

Scopus Publications

  • Beyond bacilli: integrating the microbiome into the TB research agenda
    Edson Mambuque, Ana del Amo-de Palacios, Samuel G. Huete, Charissa C. Marsh, Grant Theron, Alberto L. García-Basteiro, Sergio Serrano-Villar
    Gut Microbes, 2026
    Tuberculosis (TB) remains a leading infectious killer, with growing evidence that the human microbiome-particularly in the gut and lungs-shapes susceptibility, progression, and treatment outcomes. Over the past decade, studies have reported that TB-associated dysbiosis, which is more common in the gut than in the lung, is often marked by the loss of short-chain fatty acid-producing taxa and the expansion of opportunistic microbes. However, findings are frequently confounded by diet, antibiotic exposure, comorbidities, geography, and methodological variability. Most research has relied on compositional profiling, offering limited insight into functional mechanisms. This narrative review synthesizes recent evidence, emphasizing the need to integrate multiomics approaches-metagenomics, metatranscriptomics, and metabolomics-and experimental validation to uncover causal links between microbiome alterations and TB pathogenesis or therapy response. We discuss potential clinical applications, including microbiome-based diagnostics (such as stool-based microbial or metabolite signatures for TB risk stratification), prognostic indicators (such as gut microbiome recovery predicting immune normalization during therapy), and adjunctive interventions (including microbiome-derived products to reduce drug-induced liver injury or fecal microbiota transplantation, which has been shown to be safe in people with HIV on stable ART) to mitigate drug toxicity or enhance immune recovery. Key priorities include methodological standardization, confounder control, mechanistic studies, and the inclusion of high-burden settings. By moving beyond descriptive surveys toward functional, translational research, integrating insights from different microbiome methods into TB prevention, diagnosis, and treatment could redefine the clinical research agenda and open new avenues for precision medicine in this global disease.
  • Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen
    Samuel G. Huete, Alejandro Leyva, Etienne Kornobis, Thomas Cokelaer, Pierre Lechat, Marc Monot, Rosario Duran, Mathieu Picardeau, Nadia Benaroudj
    Mbio, 2025
    Dioxygen (O 2 ) is vital for aerobic life, but its utilization leads to the inevitable production of superoxide, a toxic oxidant. The prevailing theory of oxygen toxicity postulates that superoxide-scavenging enzymes (SOSEs), such as superoxide dismutases (SODs), are crucial for most aerobes and play a key role in the virulence of pathogens. However, our knowledge of superoxide adaptation primarily stems from the study of SOSE-encoding bacteria. Here, we investigated the evolution of a naturally SOSE-deficient pathogen ( Leptospira spp.) and its alternative mechanisms to combat superoxide stress. We demonstrated that SOD was ancestral in the genus Leptospira but lost by pathogenic species, and heterologous expression of a SOD in this pathogen did not improve superoxide tolerance. In L. interrogans , inheritable increased expression of a genetic locus, including a MFS transporter, mediated a long-lasting adaptation to superoxide, independently of any permanent genetic modification. Using a multi-omics approach, we identified a leuA2 -encoded isopropylmalate synthase, the enzyme catalyzing the first step of leucine biosynthesis, as the most upregulated factor by superoxide. Interestingly, LeuA2 lacks the canonical domain for feedback inhibition by leucine and is the only upregulated factor of leucine biosynthesis, suggesting a moonlighting activity for LeuA2 in the adaptation to superoxide. Moreover, the cysteine biosynthesis pathway was significantly upregulated in response to superoxide, and we demonstrated the importance of sulfur metabolism in adaptation to superoxide. This study revisits our conventional understanding of the oxygen toxicity theory and proposes a new model of superoxide adaptation through redox-based metabolic rewiring in SOSE-deficient aerobic bacteria. IMPORTANCE Superoxide is a toxic reactive oxygen species produced as an inevitable byproduct during oxygen respiration. It is therefore assumed that aerobic bacteria require superoxide scavenging enzymes (SOSEs), such as superoxide dismutases. Recent studies estimate that around 10% of all living organisms lack SOSEs. However, we ignore how these organisms survive superoxide stress when confronted with oxygen. Here, using Leptospira interrogans , a naturally SOSE-deficient aerobic pathogen, we address the evolutionary path and defense mechanisms leading to the adaptation to superoxide in the absence of any SOSE. We demonstrate that a SOD was ancestral in this genus but was lost with the emergence of pathogenic species. In addition, we show that pathogenic Leptospira induce metabolic pathways to fight superoxide, such as cysteine biosynthesis and isopropylmalate synthase. Thus, our study reveals that redox-based metabolic reprogramming may compensate for the loss of SOSEs in pathogenic bacteria.
  • Inter-species Transcriptomic Analysis Reveals a Constitutive Adaptation Against Oxidative Stress for the Highly Virulent Leptospira Species
    Alexandre Giraud-Gatineau, Garima Ayachit, Cecilia Nieves, Kouessi C Dagbo, Konogan Bourhy, Francisco Pulido, Samuel G Huete, Nadia Benaroudj, Mathieu Picardeau, Frédéric J Veyrier
    Molecular Biology and Evolution, 2024
    Transcriptomic analyses across large scales of evolutionary distance have great potential to shed light on regulatory evolution but are complicated by difficulties in establishing orthology and limited availability of accessible software. We introduce here a method and a graphical user interface wrapper, called Annotator-RNAtor, for performing interspecies transcriptomic analysis and studying intragenus evolution. The pipeline uses third-party software to infer homologous genes in various species and highlight differences in the expression of the core-genes. To illustrate the methodology and demonstrate its usefulness, we focus on the emergence of the highly virulent Leptospira subclade known as P1+, which includes the causative agents of leptospirosis. Here, we expand on the genomic study through the comparison of transcriptomes between species from P1+ and their related P1- counterparts (low-virulent pathogens). In doing so, we shed light on differentially expressed pathways and focused on describing a specific example of adaptation based on a differential expression of PerRA-controlled genes. We showed that P1+ species exhibit higher expression of the katE gene, a well-known virulence determinant in pathogenic Leptospira species correlated with greater tolerance to peroxide. Switching PerRA alleles between P1+ and P1- species demonstrated that the lower repression of katE and greater tolerance to peroxide in P1+ species was solely controlled by PerRA and partly caused by a PerRA amino-acid permutation. Overall, these results demonstrate the strategic fit of the methodology and its ability to decipher adaptive transcriptomic changes, not observable by comparative genome analysis, that may have been implicated in the emergence of these pathogens.
  • Taxonomy and phylogenomics of Leptospira
    Cecilia Nieves, Samuel G. Huete, Frédéric J. Veyrier, Mathieu Picardeau
    Phylogenomics Foundations Methods and Pathogen Analysis, 2024
  • The Arsenal of Leptospira Species against Oxidants
    Samuel G. Huete, Nadia Benaroudj
    Antioxidants, 2023
    Reactive oxygen species (ROS) are byproducts of oxygen metabolism produced by virtually all organisms living in an oxic environment. ROS are also produced by phagocytic cells in response to microorganism invasion. These highly reactive molecules can damage cellular constituents (proteins, DNA, and lipids) and exhibit antimicrobial activities when present in sufficient amount. Consequently, microorganisms have evolved defense mechanisms to counteract ROS-induced oxidative damage. Leptospira are diderm bacteria form the Spirochaetes phylum. This genus is diverse, encompassing both free-living non-pathogenic bacteria as well as pathogenic species responsible for leptospirosis, a widespread zoonotic disease. All leptospires are exposed to ROS in the environment, but only pathogenic species are well-equipped to sustain the oxidative stress encountered inside their hosts during infection. Importantly, this ability plays a pivotal role in Leptospira virulence. In this review, we describe the ROS encountered by Leptospira in their different ecological niches and outline the repertoire of defense mechanisms identified so far in these bacteria to scavenge deadly ROS. We also review the mechanisms controlling the expression of these antioxidants systems and recent advances in understanding the contribution of Peroxide Stress Regulators in Leptospira adaptation to oxidative stress.
  • The oxidative stress response of pathogenic Leptospira is controlled by two peroxide stress regulators which putatively cooperate in controlling virulence
    Crispin Zavala-Alvarado, Samuel G. Huete, Antony T. Vincent, Odile Sismeiro, Rachel Legendre, Hugo Varet, Giovanni Bussotti, Céline Lorioux, Pierre Lechat, Jean-Yves Coppée, Frédéric J. Veyrier, Mathieu Picardeau, Nadia Benaroudj
    Plos Pathogens, 2021
    PathogenicLeptospiraare the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverished populations. Mechanisms allowing pathogenicLeptospirato survive inside a host and induce acute leptospirosis are not fully understood. The ability to resist deadly oxidants produced by the host during infection is pivotal forLeptospiravirulence. We have previously shown that genes encoding defenses against oxidants inL.interrogansare repressed by PerRA (encoded by LIMLP_10155), a peroxide stress regulator of the Fur family. In this study, we describe the identification and characterization of another putative PerR-like regulator (LIMLP_05620) inL.interrogans. Protein sequence and phylogenetic analyses indicated that LIMLP_05620 displayed all the canonical PerR amino acid residues and is restricted to pathogenicLeptospiraclades. We therefore named this PerR-like regulator PerRB. InL.interrogans, the PerRB regulon is distinct from that of PerRA. While aperRAmutant had a greater tolerance to peroxide, inactivatingperRBled to a higher tolerance to superoxide, suggesting that these two regulators have a distinct function in the adaptation ofL.interrogansto oxidative stress. The concomitant inactivation ofperRAandperRBresulted in a higher tolerance to both peroxide and superoxide and, unlike the single mutants, a doubleperRAperRBmutant was avirulent. Interestingly, this correlated with major changes in gene and non-coding RNA expression. Notably, several virulence-associated genes (clpB,ligA/B, andlvrAB) were repressed. By obtaining a double mutant in a pathogenicLeptospirastrain, our study has uncovered an interplay of two PerRs in the adaptation ofLeptospirato oxidative stress with a putative role in virulence and pathogenicity, most likely through the transcriptional control of a complex regulatory network.
  • A case report: insights into reducing plastic waste in a microbiology laboratory
    Joana Alves, Fiona A. Sargison, Hanne Stawarz, Willow B. Fox, Samuel G. Huete, Amany Hassan, Brian McTeir, Amy C. Pickering
    Access Microbiology, 2021
    Single-use plastics have often replaced more sustainable materials in microbiology laboratories. Keeping in mind that one of the objectives of the United Nations Sustainable Development Goals is responsible consumption and production, we wanted to document how many single-use plastic items could be saved by taking reduction and reuse approaches in a microbiology laboratory. After taking 4 weeks to document the baseline levels of single-use plastic waste being generated in our laboratory and identifying ways to reduce our reliance on them, we implemented various reduction and reuse approaches and then documented our plastic use over a 7-week period. Reduction approaches included moving to sustainable materials, such as reusable wooden sticks for patch plating and metal loops for inoculation. Reuse approaches focused on reusing plastic tubes via a chemical decontamination station and autoclaving, facilitating the reduction of single-use plastics and a decrease in the amount of waste generated. By utilizing reduction and reuse strategies, which could be implemented in other microbiology laboratories, substantial single-use plastic savings were achieved. These savings had an impact on the amount of biohazard waste being autoclaved and incinerated, as well as generating substantial cost savings for the research institute. The reductions in waste documented in this study could act as a benchmark for others wanting to implement the changes described.
  • The transcriptional response of pathogenic Leptospira to peroxide reveals new defenses against infection-related oxidative stress
    Crispin Zavala-Alvarado, Odile Sismeiro, Rachel Legendre, Hugo Varet, Giovanni Bussotti, Jan Bayram, Samuel G. Huete, Guillaume Rey, Jean-Yves Coppée, Mathieu Picardeau, Nadia Benaroudj
    Plos Pathogens, 2020
    Pathogenic Leptospira spp. are the causative agents of the waterborne zoonotic disease leptospirosis. Leptospira are challenged by numerous adverse conditions, including deadly reactive oxygen species (ROS), when infecting their hosts. Withstanding ROS produced by the host innate immunity is an important strategy evolved by pathogenic Leptospira for persisting in and colonizing hosts. In L. interrogans, genes encoding defenses against ROS are repressed by the peroxide stress regulator, PerR. In this study, RNA sequencing was performed to characterize both the L. interrogans response to low and high concentrations of hydrogen peroxide and the PerR regulon. We showed that Leptospira solicit three main peroxidase machineries (catalase, cytochrome C peroxidase and peroxiredoxin) and heme to detoxify oxidants produced during peroxide stress. In addition, canonical molecular chaperones of the heat shock response and DNA repair proteins from the SOS response were required for Leptospira recovering from oxidative damage. Identification of the PerR regulon upon exposure to H2O2 allowed to define the contribution of this regulator in the oxidative stress response. This study has revealed a PerR-independent regulatory network involving other transcriptional regulators, two-component systems and sigma factors as well as non-coding RNAs that putatively orchestrate, in concert with PerR, the oxidative stress response. We have shown that PerR-regulated genes encoding a TonB-dependent transporter and a two-component system (VicKR) are involved in Leptospira tolerance to superoxide. This could represent the first defense mechanism against superoxide in L. interrogans, a bacterium lacking canonical superoxide dismutase. Our findings provide an insight into the mechanisms required by pathogenic Leptospira to overcome oxidative damage during infection-related conditions. This will participate in framing future hypothesis-driven studies to identify and decipher novel virulence mechanisms in this life-threatening pathogen.
  • Improving the serodiagnosis of canine Leishmania infantum infection in geographical areas of Brazil with different disease prevalence
    Laura Ramírez, Luana Dias de Moura, Natalia Lopes Fontoura Mateus, Milene Hoehr de Moraes, Leopoldo Fabrício Marçal do Nascimento, Nailson de Jesus Melo, Lucas Bezerra Taketa, Tatiana Catecati, Samuel G. Huete, Karla Penichet, Eliane Mattos Piranda, Alessandra Gutierrez de Oliveira, Mario Steindel, Manoel Barral-Netto, Maria do Socorro Pires e Cruz, Aldina Barral, Manuel Soto
    Parasite Epidemiology and Control, 2020
    Serodiagnosis of Leishmania infantum infection in dogs relies on the detection of antibodies against leishmanial crude extracts or parasitic defined antigens. The expansion of canine leishmaniasis from geographical areas of Brazil in which the infection is endemic to regions in which the disease is emerging is occurring. This fact makes necessary the analysis of the serodiagnostic capabilities of different leishmanial preparations in distinct geographical locations. In this article sera from dogs infected with Leishmania and showing the clinical form of the disease, were collected in three distinct Brazilian States and were tested against soluble leishmanial antigens or seven parasite individual antigens produced as recombinant proteins. We show that the recognition of soluble leishmanial antigens by sera from these animals was influenced by the geographical location of the infected dogs. Efficacy of the diagnosis based on this crude parasite preparation was higher in newly endemic regions when compared with areas of high disease endemicity. We also show that the use of three of the recombinant proteins, namely parasite surface kinetoplastid membrane protein of 11 kDa (KMP-11), and two members of the P protein family (P2a and P0), can improve the degree of sensitivity without adversely affecting the specificity of the diagnostic assays for canine leishmaniasis, independently of the geographical area of residence. In addition, sera from dogs clinically healthy but infected were also assayed with some of the antigen preparations. We demonstrate that the use of these proteins can help to the serodiagnosis of Leishmania infected animals with subclinical infections. Finally, we propose a diagnostic protocol using a combination of KMP-11, P2a y P0, together with total leishmanial extracts.

RECENT SCHOLAR PUBLICATIONS

  • Beyond bacilli: integrating the microbiome into the TB research agenda
    E Mambuque, A Del Amo-de Palacios, SG Huete, CC Marsh, G Theron, ...
    Gut Microbes 18 (1), 2638004 , 2026
    2026.0
  • Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen
    SG Huete, A Leyva, E Kornobis, T Cokelaer, P Lechat, M Monot, R Duran, ...
    mBio 16 (8), e0064525 , 2025
    2025.0
    Citations: 2
  • Linking genomic evolutionary transitions to ecological phenotypic adaptations in Spirochaetes
    SG Huete, K Coullin, E Chapeaublanc, R Torchet, N Benaroudj, ...
    bioRxiv , 2025
    2025.0
    Citations: 1
  • Evolutionary adaptation of pathogenic Leptospira to superoxide stress
    SG Huete
    Université Paris Cité , 2024
    2024.0
  • Taxonomy and phylogenomics of Leptospira
    C Nieves, SG Huete, F Veyrier, M Picardeau
    Phylogenomics: Foundations, Methods, and Pathogen Analysis , 2024
    2024.0
    Citations: 7
  • Inter-species Transcriptomic Analysis Reveals a Constitutive Adaptation Against Oxidative Stress for the Highly Virulent Leptospira Species
    A Giraud-Gatineau, G Ayachit, C Nieves, KC Dagbo, K Bourhy, F Pulido, ...
    Molecular Biology and Evolution 41 (4), msae066 , 2024
    2024.0
    Citations: 8
  • Pan-species transcriptomic analysis reveals a constitutive adaptation against oxidative stress for the highly virulent Leptospira species
    A Giraud-Gatineau, G Ayachit, C Nieves, KC Dagbo, K Bourhy, F Pulido, ...
    bioRxiv, 2023.08. 01.551416 , 2023
    2023.0
    Citations: 1
  • The Arsenal of Leptospira Species against Oxidants
    SG Huete, N Benaroudj
    Antioxidants 12 (6), 1273 , 2023
    2023.0
    Citations: 8
  • The Arsenal of Leptospira Species against Oxidants. Antioxidants 2023, 12, 1273
    SG Huete, N Benaroudj
    2023.0
  • The oxidative stress response of pathogenic Leptospira is controlled by two peroxide stress regulators which putatively cooperate in controlling virulence
    C Zavala-Alvarado, S G. Huete, AT Vincent, O Sismeiro, R Legendre, ...
    PLoS Pathogens 17 (12), e1009087 , 2021
    2021.0
    Citations: 16
  • The transcriptional response of pathogenic Leptospira to peroxide reveals new defenses against infection-related oxidative stress
    C Zavala-Alvarado, O Sismeiro, R Legendre, H Varet, G Bussotti, ...
    PLoS pathogens 16 (10), e1008904 , 2020
    2020.0
    Citations: 31
  • Improving the serodiagnosis of canine Leishmania infantum infection in geographical areas of Brazil with different disease prevalence
    L Ramírez, LD de Moura, NLF Mateus, MH de Moraes, ...
    Parasite Epidemiology and Control 8, e00126 , 2020
    2020.0
    Citations: 8
  • A case report: insights into reducing plastic waste in a microbiology laboratory.
    J Alves, FA Sargison, H Stawarz, WB Fox, SG Huete, A Hassan, B McTeir, ...
    Access Microbiology , 2020
    2020.0
    Citations: 92
  • A case report: insights into reducing plastic waste in a microbiology laboratory. Access Microbiol. 2021
    J Alves, FA Sargison, H Stawarz, WB Fox, SG Huete, A Hassan, B McTeir, ...
    Citations: 5

MOST CITED SCHOLAR PUBLICATIONS

  • A case report: insights into reducing plastic waste in a microbiology laboratory.
    J Alves, FA Sargison, H Stawarz, WB Fox, SG Huete, A Hassan, B McTeir, ...
    Access Microbiology , 2020
    2020.0
    Citations: 92
  • The transcriptional response of pathogenic Leptospira to peroxide reveals new defenses against infection-related oxidative stress
    C Zavala-Alvarado, O Sismeiro, R Legendre, H Varet, G Bussotti, ...
    PLoS pathogens 16 (10), e1008904 , 2020
    2020.0
    Citations: 31
  • The oxidative stress response of pathogenic Leptospira is controlled by two peroxide stress regulators which putatively cooperate in controlling virulence
    C Zavala-Alvarado, S G. Huete, AT Vincent, O Sismeiro, R Legendre, ...
    PLoS Pathogens 17 (12), e1009087 , 2021
    2021.0
    Citations: 16
  • Inter-species Transcriptomic Analysis Reveals a Constitutive Adaptation Against Oxidative Stress for the Highly Virulent Leptospira Species
    A Giraud-Gatineau, G Ayachit, C Nieves, KC Dagbo, K Bourhy, F Pulido, ...
    Molecular Biology and Evolution 41 (4), msae066 , 2024
    2024.0
    Citations: 8
  • The Arsenal of Leptospira Species against Oxidants
    SG Huete, N Benaroudj
    Antioxidants 12 (6), 1273 , 2023
    2023.0
    Citations: 8
  • Improving the serodiagnosis of canine Leishmania infantum infection in geographical areas of Brazil with different disease prevalence
    L Ramírez, LD de Moura, NLF Mateus, MH de Moraes, ...
    Parasite Epidemiology and Control 8, e00126 , 2020
    2020.0
    Citations: 8
  • Taxonomy and phylogenomics of Leptospira
    C Nieves, SG Huete, F Veyrier, M Picardeau
    Phylogenomics: Foundations, Methods, and Pathogen Analysis , 2024
    2024.0
    Citations: 7
  • A case report: insights into reducing plastic waste in a microbiology laboratory. Access Microbiol. 2021
    J Alves, FA Sargison, H Stawarz, WB Fox, SG Huete, A Hassan, B McTeir, ...
    Citations: 5
  • Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen
    SG Huete, A Leyva, E Kornobis, T Cokelaer, P Lechat, M Monot, R Duran, ...
    mBio 16 (8), e0064525 , 2025
    2025.0
    Citations: 2
  • Linking genomic evolutionary transitions to ecological phenotypic adaptations in Spirochaetes
    SG Huete, K Coullin, E Chapeaublanc, R Torchet, N Benaroudj, ...
    bioRxiv , 2025
    2025.0
    Citations: 1
  • Pan-species transcriptomic analysis reveals a constitutive adaptation against oxidative stress for the highly virulent Leptospira species
    A Giraud-Gatineau, G Ayachit, C Nieves, KC Dagbo, K Bourhy, F Pulido, ...
    bioRxiv, 2023.08. 01.551416 , 2023
    2023.0
    Citations: 1
  • Beyond bacilli: integrating the microbiome into the TB research agenda
    E Mambuque, A Del Amo-de Palacios, SG Huete, CC Marsh, G Theron, ...
    Gut Microbes 18 (1), 2638004 , 2026
    2026.0
  • Evolutionary adaptation of pathogenic Leptospira to superoxide stress
    SG Huete
    Université Paris Cité , 2024
    2024.0
  • The Arsenal of Leptospira Species against Oxidants. Antioxidants 2023, 12, 1273
    SG Huete, N Benaroudj
    2023.0