Stephen B. Beres

Stephen B. Beres, PhD

Research Professor of Pathology and Genomic Medicine, Academic Institute
Full Research Member, Research Institute
Houston Methodist


Biography

After earning his PhD in Molecular Biology in 1995 from Northwestern University, Dr. Beres completed post-doctoral fellowships at Baylor College of Medicine and the National Institute of Allergy and Infectious Diseases. Dr. Beres joined the Houston Methodist Research Institute HMRI at its inception in 2006, where he is currently a Full Research Member, Research Institute, Professor, Academic Institute, and Director of Microbial Informatics for the Center for Molecular and Translational Human Infectious Disease Research. Dr. Beres’s research focuses on employing bacterial whole-genome sequencing to understand human infectious diseases caused by microbial pathogens, including Streptococcus pyogenes, Staphylococcus aureus, and Klebsiella pneumoniae.

Description of Research

The primary focus of Dr. Beres’s research is identifying the genetic/genomic basis for intrinsic differences and adaptive changes in the pathogenic behavior of human bacterial infections. Over the last 17 years, Dr. Beres has used bacterial pathogen whole-genome sequencing and related genome-scale strategies on populations of hundreds to thousands of human clinical isolates to obtain initial genomic assessments. Dr. Beres has then used DNA sequencing to further analyze strain-to-strain variation in gene content and RNA/cDNA sequencing for genome-wide gene transcriptome assessment. Dr. Beres is one of few specialists who has focused particularly on the human bacterial pathogen S. pyogenes, colloquially referred to as the “flesh-eating” bacteria. Dr. Beres’s research has contributed 40 of 166 (24%) of the complete genome sequences for S. pyogenes that are currently in the National Center Biotechnology Information GenBank database.

One prominent theme of Dr. Beres’s research has been the use of population pathogenomics to determine the molecular genetic underpinnings responsible for the epidemic shifts of different S. pyogenes genotypes that are responsible for severe invasive infections with high human morbidity and mortality. One important discovery of his research is that recurrent epidemic waves of type emm3 S. pyogenes stemmed from the emergence of newly evolved strains with enhanced fitness, and not from recycling of the same clone responsible for the preceding wave. Similarly, his analysis of 3,615 samples of type emm1 S. pyogenes obtained from global sources found that only four molecular genetic events were responsible for the pandemic of severe invasive infections worldwide. He also discovered that an emm89 S. pyogenes epidemic clone evolved through a complex series of multiple horizontal-transfer genetic recombination events, one of which was virtually identical to the recombination event responsible for triggering the pandemic of invasive infections caused by the emm1 strain. These three studies are some of the largest population pathogenomic infectious disease investigations that have been conducted.

Publications

Integrating genomics, transcriptomics and virulence to study Streptococcus dysgalactiae subspecies equisimilis (SDSE) strains causing severe infections in humans
Eraso, JM, Beres, SB, Olsen, RJ, Long, SW, Gadd, R, Boukthir, S, Faili, A, Kayal, S & Musser, JM 2023, , Tissue, Matrix & Pathobiology Meeting, Salt lake City, United States, 10/22/23 - 10/25/23.

Analysis of the Genomics and Mouse Virulence of an Emergent Clone of Streptococcus dysgalactiae Subspecies equisimilis
Beres, SB, Olsen, RJ, Wesley Long, S, Eraso, JM, Boukthir, S, Faili, A, Kayal, S & Musser, JM 2023, , Microbiology Spectrum, vol. 11, no. 2. https://doi.org/10.1128/spectrum.04550-22

Genome-Wide Transposon Mutagenesis Screens Identify Group A Streptococcus Genes Affecting Susceptibility to ß-Lactam Antibiotics
Zhu, L, Eraso, JM, Mangham, RE, Saavedra, MO, Olsen, RJ, Beres, SB & Musser, JM 2022, , Journal of bacteriology, vol. 204, no. 12. https://doi.org/10.1128/jb.00287-22

A Chimeric Penicillin Binding Protein 2X Significantly Decreases in Vitro Beta-Lactam Susceptibility and Increases in Vivo Fitness of Streptococcus pyogenes
Olsen, RJ, Zhu, L, Mangham, RE, Faili, A, Kayal, S, Beres, SB & Musser, JM 2022, , American Journal of Pathology, vol. 192, no. 10, pp. 1397-1406. https://doi.org/10.1016/j.ajpath.2022.06.011

Integrative Reverse Genetic Analysis Identifies Polymorphisms Contributing to Decreased Antimicrobial Agent Susceptibility in Streptococcus pyogenes
Beres, SB, Zhu, L, Pruitt, L, Olsen, RJ, Faili, A, Kayal, S & Musser, JM 2022, , mBio, vol. 13, no. 1, e03618, pp. e0361821. https://doi.org/10.1128/MBIO.03618-21

Genome-wide transposon mutagenesis screens identify group A streptococcus genes affecting susceptibility to beta-lactam antibiotics
Zhu, L, Eraso, JM, Mangham, R, Ojeda Saavedra, M, Olsen, RJ, Beres, SB & Musser, JM 2022, , Journal of bacteriology. https://doi.org/10.1128/jb.00287-22

Functional insights into the high-molecular-mass penicillin- binding proteins of streptococcus agalactiae revealed by gene deletion and transposon mutagenesis analysis
Zhu, L, Yerramilli, P, Pruitt, L, Mishra, A, Olsen, RJ, Beres, SB, Waller, AS & Musser, JM 2021, , Journal of bacteriology, vol. 203, no. 17, e00234-21, pp. e0023421. https://doi.org/10.1128/JB.00234-21

Genetic basis underlying the hyperhemolytic phenotype of streptococcus agalactiae strain CNCTC10/84
Zhu, L, Beres, SB, Yerramilli, P, Pruitt, L, Cantu, CC, Olsen, RJ & Musser, JM 2020, , Journal of bacteriology, vol. 202, no. 23, e00504-20. https://doi.org/10.1128/JB.00504-20

Genome-wide assessment of streptococcus agalactiae genes required for survival in human whole blood and plasma
Zhu, L, Yerramilli, P, Pruitt, L, Saavedra, MO, Cantu, CC, Olsen, RJ, Beres, SB, Waller, AS & Musser, JM 2020, , Infection and Immunity, vol. 88, no. 10, e00357. https://doi.org/10.1128/IAI.00357-20

Population genomic molecular epidemiological study of macrolide-resistant streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a large clonal population with a pbp2x mutation conferring reduced in vitro ß-Lactam Susceptibility
Southon, SB, Beres, SB, Kachroo, P, Saavedra, MO, Erlendsdóttir, H, Haraldsson, G, Yerramilli, P, Pruitt, L, Zhu, L, Musser, JM & Kristinsson, KG 2020, , Journal of Clinical Microbiology, vol. 58, no. 9, e00638-20. https://doi.org/10.1128/JCM.00638-20

Streptococcus pyogenes genes that promote pharyngitis in primates
Zhu, L, Olsen, RJ, Beres, SB, Saavedra, MO, Kubiak, SL, Cantu, CC, Jenkins, L, Waller, AS, Sun, Z, Palzkill, T, Porter, AR, DeLeo, FR & Musser, JM 2020, , JCI insight, vol. 5, no. 11, e137686. https://doi.org/10.1172/jci.insight.137686

Population genomic molecular epidemiological study of macrolide resistant Streptococcus pyogenes in Iceland, 1995-2016: Identification of a large clonal population with a pbp2x mutation conferring reduced in vitro b-lactam susceptibility
Southon, SB, Beres, SB, Kachroo, P, Saavedra, MO, Erlendsdóttir, H, Haraldsson, G, Yerramilli, P, Pruitt, L, Zhu, L, Musser, JM & Kristinsson, KG 2020, , Unknown Journal. https://doi.org/10.1101/2020.05.12.090365

Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women in Finland
Gröndahl-Yli-Hannuksela, K, Beres, SB, Hyyryläinen, HL, Kallonen, T, Musser, JM & Vuopio, J 2021, , Clinical Microbiology and Infection, vol. 27, no. 3, pp. 420-427. https://doi.org/10.1016/j.cmi.2020.04.004

Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence
Zhu, L, Olsen, RJ, Beres, SB, Ojeda Saavedra, M, Kubiak, SL, Cantu, CC, Jenkins, L, Yerramilli, P, Pruitt, L, Charbonneau, ARL, Waller, AS & Musser, JM 2020, , American Journal of Pathology, vol. 190, no. 4, pp. 862-873. https://doi.org/10.1016/j.ajpath.2019.12.003

Reduced in vitro susceptibility of streptococcus pyogenes to ß-lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread
Musser, JM, Beres, SB, Zhu, L, Olsen, RJ, Vuopio, J, Hyyryläinen, HL, Gröndahl-Yli-Hannuksela, K, Kristinsson, KG, Darenberg, J, Henriques-Normark, B, Hoffmann, S, Caugant, DA, Smith, AJ, Lindsay, DSJ, Boragine, DM & Palzkill, T 2020, , Journal of Clinical Microbiology, vol. 58, no. 4, e01993-19. https://doi.org/10.1128/JCM.01993-19

Genetic heterogeneity of the Spy1336/R28—Spy1337 virulence axis in Streptococcus pyogenes and effect on gene transcript levels and pathogenesis
Eraso, JM, Kachroo, P, Olsen, RJ, Beres, SB, Zhu, L, Badu, T, Shannon, S, Cantu, CC, Saavedra, MO, Kubiak, SL, Porter, AR, DeLeo, FR & Musser, JM 2020, , PLoS ONE, vol. 15, no. 3, e0229064. https://doi.org/10.1371/journal.pone.0229064

Genetic heterogeneity of the Spy1336/R28 - Spy1337 virulence axis in streptococcus pyogenes and effect on gene transcript levels and pathogenesis
Eraso, JM, Kachroo, P, Olsen, RJ, Beres, SB, Zhu, L, Badu, T, Shannon, S, Cantu, CC, Saavedra, MO, Kubiak, SL, Porter, AR, DeLeo, FR & Musser, JM 2019, , Unknown Journal. https://doi.org/10.1101/777987

Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis
Kachroo, P, Eraso, JM, Beres, SB, Olsen, RJ, Zhu, L, Nasser, W, Bernard, PE, Cantu, CC, Saavedra, MO, Arredondo, MJ, Strope, B, Do, H, Kumaraswami, M, Vuopio, J, Gröndahl-Yli-Hannuksela, K, Kristinsson, KG, Gottfredsson, M, Pesonen, M, Pensar, J, Davenport, ER, Clark, AG, Corander, J, Caugant, DA, Gaini, S, Magnussen, MD, Kubiak, SL, Nguyen, HAT, Long, SW, Porter, AR, DeLeo, FR & Musser, JM 2019, , Nature Genetics, vol. 51, no. 3, pp. 548-559. https://doi.org/10.1038/s41588-018-0343-1

Gene fitness landscape of group A streptococcus during necrotizing myositis
Zhu, L, Olsen, RJ, Beres, SB, Eraso, JM, Saavedra, MO, Kubiak, SL, Cantu, CC, Jenkins, L, Charbonneau, ARL, Waller, AS & Musser, JM 2019, , The Journal of clinical investigation, vol. 129, no. 2, pp. 887-901. https://doi.org/10.1172/JCI124994

RocA has serotype-specific gene regulatory and pathogenesis activities in serotype M28 Group A streptococcus
Bernard, PE, Kachroo, P, Zhu, L, Beres, SB, Eraso, JM, Kajani, Z, Long, SW, Musser, JM & Olsen, RJ 2018, , Infection and Immunity, vol. 86, no. 11, e00467-18. https://doi.org/10.1128/IAI.00467-18