Image of Ehrlich, Garth

Garth D. Ehrlich, PhD

Professor of Microbiology & Immunology; Professor of Otolaryngology-Head and Neck Surgery

  • Department:Microbiology and Immunology
  • Education: PhD, Syracuse University, Syracuse, N.Y. (1987)
Research Overview

Dr. Ehrlich is the executive director of the Center for Advanced Microbial Processing (CAMP) and the Center for Genomic Sciences, both within the Institute for Molecular Medicine & Infectious Disease. He also serves as executive director of the Genomics Core Facility, which is part of the Clinical and Translational Research Institute.

Dr. Ehrlich's research explores the molecular pathogenesis of chronic infectious diseases.

In the News

"Two Drexel Faculty Members Named 2014 AAAS Fellows"
(December 8, 2014)

"Thwarting Persistence"
The-Scientist.com (November 13, 2013)

 

Research

Chronic Bacterial Pathogenesis

We are interested in how chronic bacterial pathogens persist in the face of antimicrobial therapy and the adaptive host response. To understand this complex phenomenon, we have promulgated the rubric of “Bacterial Plurality” which embodies the concept that chronic pathogens display enormous heterogeneity at many levels including: phenotypic, metabolic, and genotypic. The reasoning behind the development of this theoretical construct was to provide a paradigm that more accurately models chronic pathogenic processes so that it will be possible to develop rational therapies for these recalcitrant diseases. It is our belief that the extant paradigms of bacterial pathogenesis passed down to us from Robert Koch and developed for acute epidemic infections, although powerful and useful for clonal planktonic infections, acted for decades as blinders towards our understanding of chronic infections.

As part of our studies of bacterial plurality we have participated in the development of a new understanding of bacterial ecology, which includes the realization that bacteria have a developmental life cycle, can exist as solitary organisms or as part of a complex interacting multicellular community, and can phenotypically adapt to changing environmental conditions. Phenotypic heterogeneity is explained by the fact that nearly all bacteria can form biofilms or even more complex ordered large-scale structures for protection, generation of reducing power, and dispersal; metabolic heterogeneity by the understanding of limiting nutrient fluxes into a biofilm, and genotypic heterogeneity by the distributed genome hypothesis (DGH) which we advanced in 2001. The DGH states that chronic bacterial pathogens utilize a survival strategy wherein a large set of genes are distributed among a population and are not found in all members of a species; thus there exists a supra-genome at the population level which is far greater in size than the genome of any one organism. The DGH includes the concept that energetic methods of horizontal gene transfer (HGT) are population-based virulence factors that evolved specifically to create diversity and drive strain evolution and that the distribution of contingency genes among a population serves as a supra-virulence factor that provides for improved population survival through increased rates of horizontal gene transfer which provides the engine for rapid adaptation to environmental conditions through the reassortment of genes among strains.

Using the massively parallel pyrosequencing technology of 454 LifeSciences and a suite of bioinformatic and mathematical modeling tools developed in-house we have: 1) performed whole genome sequencing on over 100 clinical strains of pathogenic bacteria representing six species; and 2) performed comparative genomics on over 400 bacterial strains representing 24 species. The data from these studies have demonstrated that the DGH holds for all bacterial species examined including pathogens and nonpathogens alike; and that the supragenomes for most of these species are several times the size of the species’ core genomes. Importantly the species examined cover gram-negatives, gram-positives, gram-indeterminates, spirochetes, professional pathogens, opportunistic pathogens, and free-living environmental and commensal organisms. We therefore feel comfortable in stating that the DGH is broadly applicable across the entire spectrum of free-living bacteria and that bacterial diversity provides bacterial species, as a whole – regardless of their individual environmental niches, with the ability to persist in the face of multi-faceted attacks.

More recently we have been expanding the concept of population-based virulence factors which include phenomena that exist only at the population-level and are thus nonobservable at the level of the individual bacterium. These include biofilm formation, caserna construction, and other complex cellular organizations such as nanowires; bacterial communication systems such as quorum sensing and vesicle formation and dispersement; and horizontal gene transfer mechanisms. Collectively these systems imbue bacteria with a type of intelligence analogous to cellular automation.

Human Disease, Susceptibility, and Performance Gene Mapping and Cloning

We are involved in a number of human gene identification projects which utilize microsatellite-based mapping, SNP-based mapping and gene association studies, and candidate gene cloning technologies. Toward this end we have heavily invested in high throughput genomic and expressomic technologies and the bioinformatic infrastructure to support these endeavors. Our laboratory has mapped genes for Crouzon syndrome, hereditary pancreatitis, DAIA, ectrodactyly, severe pediatric GERD, and Dupuytren’s contracture; and cloned genes for Crouzon and Jackson-Weiss syndromes and hereditary pancreatitis. Ongoing studies include cloning the Dupuytren’s gene, and mapping genes associated with human performance through a grant from the United States Air Force.

Publications

Selected Publications (See all Garth Ehrlich's publications in PubMed.)

"There is a specific response to pH by isolates of Haemophilus influenzae and this has a direct influence on biofilm formation"
Ishak N, Tikhomirova A, Bent SJ, Ehrlich GD, Hu FZ, and Kidd SP
BMC Microbiol;14(1):47, Feb 21 2014.

"Design and Validation of a Supragenome Hybridization Array for Determination of the Genomic Content of Haemophilus influenzae Isolates"
Eutsey R, Hiller NL, Earl J, Janto B, Dahlgren M, Ahmed A, Powell A, Schultz M, Gilsdorf J, Zhang L, Smith A, Murphy T, Sethi S, Post JC, Hu FZ, Ehrlich GD
BMC Genomics. 14:484, 2013.

"The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection"
Boase S, Foreman A, Cleland E, Tan, L., Melton-Kreft R, Pant H, Hu FZ, Ehrlich GD, and Warmold PJ
BMC Infectious Diseases 13:210, 2013. doi:10.1186/1471-2334-13-210. BMC Highly accessed article

"Capsular switch between two highly related Streptococcus pneumoniae strains only partially recreates the more virulent phenotype"
Hu FZ, Eutsey R, Ahmed A, Frazao N, Powell E, Hiller NL, Hillman T, Buchinsky FJ, Boissy R, Janto B, Bennett J, Longwell M, Ezzo S, Post JC., Tomasz A, Ehrlich GD
PLoS One 7(11):e47983, 2012.

"Comparison of PCR/Electron spray Ionization - Time-of-Flight - Mass Spectrometry versus Traditional Clinical Microbiology for Detection of Organisms Contaminating High-use Surfaces in a Burn Unit, an Orthopaedic Ward and Healthcare Workers"
Yun HC, Kreft HE., Castillo MA., Ehrlich GD, Guymon CH, Crouch HK, Chung KK, Wenke JC, Hsu JR, Spirk T, Costerton JW, Mende K, and Murray CK
BMC Infectious Diseases (Oct 10) 12:252, 2012.

"Successful Identification of Pathogens by Polymerase Chain Reaction (PCR)-Based Electron Spray Ionization Time-of-Flight Mass Spectrometry (ESI-TOF-MS) in Culture-Negative Periprosthetic Joint Infection"
Jacovides C, Kreft R, Adeli B, Hozack B, Ehrlich GD, and Parvizi J
Journal of Bone and Joint Surgery 94(24)2247-2254, 2012.

"Comparative genomic analyses of seventeen clinical isolates of Gardnerella vaginalis provides evidence of multiple genetically isolated clades consistent with sub-speciation into genovars"
Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, Powell E, Janto B, Eutsey R, Hiller NL, Boissy R, Dahlgren ME, Hall BG, Costerton JW, Post JC, Hu FZ, and Ehrlich GD
Journal of Bacteriology, 194(15):3922-37, 2012.

"Comparative Genomics of Phenotypically Diverse Clinical Pandemic Multidrug-Resistant Streptococcus pneumoniae Strains from the PMEN1 lineage"
Hiller NL, Eutsey RA, Powell E, Earl J, Janto B, Martin D, Dawid S, Ahmed A, Longwell M, Dahlgren M, Ezzo S, Tettelin S, Daugherty SC, Mitchel TC, Hillman T, Buchinsky FJ, Tomasz A, de Lencastre H, Post JC, Hu FZ, and Ehrlich GD
PLoS ONE 6(12):e28850, 2011.

"Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743"
Rath CM, Janto B, Earl J, Ahmed A, Hu FZ, Hiller NL, Dahlgren M, Kreft M, Yu F, Wolff JJ, Kweon HK, Christiainsen MA, Håkansson K, Williams RM, Ehrlich GD, Sherman, DH
ACS Chemical Biology 6(11):1244-56, 2011.

"The genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4"
Janto B, Ahmed A, Ito M, Liu J, Hicks DB, Pagni S, Fackelmayer O, Smith T-A, Earl J, Elbourne L, Paulsen I, Kolstø A-B, Tourasse NJ, Ehrlich GD, Boissy R, Ivey DM, Li G, Xue Y, Ma Y, Hu HZ, and Krulwich TA
Environmental Microbiology 13(12):3289-3309, 2011.

"Characterization of microbial communities in non-healed versus healed lower extremity venous insufficiency wounds using conventional culture and molecular diagnostic methods"
Tuttle MS, Mostow E, Mukherjee P, Hu FZ Melton-Kreft R, Ehrlich GD, Dowd SE, and Ghannoum MA
Journal of Clinical Microbiology 49(11)3812-9, 2011.

"Comparative Supragenomic Analyses among the Pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae Using a Modification of the Finite Supragenome Model"
Boissy R, Ahmed A, Janto B, Earl J, Hall BJ, Hogg J, Pusch GD, Hiller NL, Powell E, Hayes J, Yu S, Kathju S, Stoodley P, Post JC, Ehrlich GD, and Hu FZ
BMC Genomics 12:187, 2011.

"Comparative Analysis and Supragenome Modeling of Twelve Moraxella catarrhalis Clinical Isolates"
Davie JJ, Earl J, de Vries SPW, Ahmed A, Hu FZ, Bootsma HJ, Stol K, Hermans PWM, Wadowsky RM, Ehrlich GD, Hays J, Campagnari AA.
BMC Genomics 12(1):70, 2011.

"Pathogenic Biofilms in Adenoids: a Reservoir for Persistent Bacteria"
Nistico L, Gieseke A, Kreft R, Coticchia JM, Burrows A, Khampang P, Liu Y, Kerschner JE, Post JC, Ehrlich GD, Stoodley P, Hall-Stoodley L
Journal of Clinical Microbiology 49(4):1411-20, 2011.

"Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species"
Donati C, Hiller NL, Tettelin H, Muzzi A, Croucher NJ, Angiuoli SV, Oggioni M, Riley D, Covacci A, Bentley SD, Kilian M, Ehrlich GD, Hu FZ, Rappuoli R, Moxon ER, and Masignani V
Genome Biology 11(10):R107, 2010. This manuscript has ~ 80 citations

Teaching

Dr. Ehrlich is a professor in the Departments of Microbiology & Immunology and Otolaryngology-Head and Neck Surgery.

Research Location

Department of Microbiology & Immunology
245 N. 15th Street
Philadelphia, PA 19102
Phone: 215-762-1878

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