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The Fight Against Antibiotic-Resistant Pathogenic Bacteria: A New Era

FREE

for Members

The Fight Against Antibiotic-Resistant Pathogenic Bacteria: A New Era

Wednesday, October 12, 2011

The New York Academy of Sciences

The unchecked use of antibiotics since their discovery over 70 years ago has compromised their effectiveness, resulting in the rapid evolution of drug resistance. This includes drug-resistance genes on mobile genetic elements that are able to spread rapidly within and between species. The absence of antibiotic discovery programs in most pharmaceutical companies and the limited success in developing novel compounds has exacerbated the problem. The talks will cover the gravity of antibiotic resistance which has led to alternative strategies, including phage therapy, antibody treatment, inhibitory peptides, and immunomodulators. New anti-infectives being developed include exploiting bacteriophage, in which systems have evolved to rapidly kill pathogenic bacteria. One such system involves purified bacteriophage lysins, used in microgram to sub-microgram quantities to rapidly kill disease bacteria on mucous membrane surfaces, infected tissues, and in blood. These small amounts of purified lysins are able to sterilize a 107 bacterial suspension in seconds to minutes, offering a novel alternative to antibiotics. In addition, the binding domain of phage lysins has evolved to target essential structures in the gram-positive cell wall that the bacteria cannot easily alter. Using this information, strategies have been developed to identify novel pathways in the gram-positive organism that are targets for antibiotics with reduced potential for resistance.

Agenda

Welcome and Introduction
Jennifer Henry, PhD, The New York Academy of Sciences
Shirley Raps, PhD, Hunter College, CUNY

The Confounding Issues Regarding Antibiotic Resistance - A No-Win Battle!
Barry Kreiswirth, PhD, UMDNJ

Using what Bacteriophage have Learned to Develop Novel Tools for Treating Gram-Positive Infections
Vincent A. Fischetti, PhD, The Rockefeller University

Networking reception to follow

Registration Pricing

Member:$0
Student / Postdoc / Fellow Member:$0
Nonmember:$30
Student / Postdoc / Fellow Nonmember:$15


Image Credit: Pauline Yoong and Vincent A. Fischetti, Rockefeller University

Speakers

Organizers

Shirley Raps, PhD

Hunter College, CUNY

Shirley Raps, Professor and Chair of the Department of Biological Sciences at Hunter College of CUNY, has been a member of the Microbiology Section of the NYAS for many years. Her research has involved characterizing Microcystis aeruginosa strain UV027, a fresh water, toxin-producing cyanobacterium known to be a health hazard to animals and humans. 

She is also involved in science education as Director of an HHMI Undergraduate Science Education Grant to Hunter College. The grant funds promoting research by undergraduates at Hunter College, at the Marine Biological laboratory and the Cold Spring Harbor Laboratories to encourage research careers via PhD or MD/PhD programs. The grant also funds an Outreach Program to high school and middle school teachers and their students with the goal of increasing the interest in science/scientific research among pre-college students.

Jennifer Henry, PhD

The New York Academy of Sciences

Speakers

Vincent A. Fischetti, PhD

The Rockefeller University

Dr. Fischetti has over 40 years experience in the anti-infectives field. He is Professor and Chairman of the Laboratory of Bacterial Pathogenesis and Immunology at the Rockefeller University, in NY. Over those years his laboratory has been involved in understand the earliest events in gram-positive bacterial infection, so that strategies may be devised to interfere with these processes to prevent infection. Dr. Fischetti is a fellow of the American Academy of Microbiology, and is the recipient of two NIH MERIT awards. He has been editor-in-chief of the scientific journal Infection and Immunity for 10 years, and serves as advisory editor for a number of journals. Dr. Fischetti serves on the scientific advisory board and is a trustee of the Trudeau Institute. He is also serves as the chair of the SAB of ContraFect. He has published approximately 185 primary research articles, and over 70 textbook chapters as well as being an inventor of over 50 issued patents. Dr. Fischetti received a Ph.D. in Microbiology from New York University.

Barry Kreiswirth, PhD

UMDNJ

Barry Kreiswirth joined the Public Health Research (PHRI) in 1978 as a graduate student in Richard Novick's laboratory to work on the molecular biology of Staphylococcus aureus. His doctoral thesis was on the cloning of this bacterium and the genetic characterization of its toxic shock syndrome (TSS) toxin-1. Kreiswirth remained in the Novick laboratory as a post-doctoral fellow and research assistant, continuing his investigation into the molecular epidemiology of methicillin-resistant S. aureus (MRSA). Fourteen years later, in response to the New York City outbreak, Kreiswirth became the director of PHRI's Tuberculosis Center. However, despite the extensive investment in tuberculosis research, the Center has not abandoned its interest in the molecular typing of MRSA and recently developed a rapid DNA-sequenced-based genotyping method enabling scientists to accurately sub-speciate strains of staphylococcus. This approach has been adapted to identify a variety of hospital-acquired pathogens and is now used to construct a nosocomial surveillance database in collaboration with the New Jersey Department of Health and Hospitals.

Abstracts

The Confounding Issues Regarding Antibiotic Resistance — A No-Win Battle!
Barry Kreiswirth, PhD, UMDNJ

In 1969, Surgeon General William H. Stewart declared an end to the era of infectious diseases, as antibiotic pipelines were overflowing and the threat of drug resistant strains limited. What Stewart could not predict was the large increase in immunosuppressed patients, both the result of HIV disease and active suppression for transplantation surgery and other heroic medical efforts. As such, advancements in medicine enabled patients with otherwise life threatening diseases to live longer, commonly with the aid of anti-infectives. After 70 years of unabated use, the effectiveness of our most potent antimicrobials are being compromised evidenced in the remarkable and rapid evolution of drug resistance mechanisms, many on mobile genetic elements that are able to spread within and between species. The recent emergence of community acquired methicillin resistant S. aureus (MRSA), extensively drug resistant (XDR) M. tuberculosis and carbapenem resistant Enterobacteriaceae are highly drug resistant strains that have limited treatment options. Compounding this problem is the hollow antibiotic pipeline, the absence of antibiotic discovery programs in most pharmaceutical companies, and the limited success in developing novel compounds. Advancements in diagnostics, including real-time nucleic amplification platforms at the bedside, can enhance prudent use of antibiotics however has yet to be integrated in our healthcare setting. The gravity of antibiotic resistance has consequently led to alternative strategies, including phage therapy, antibody treatment, inhibitory peptides, and immunomodulators; but similar to our dependence on oil, we remain hooked on antibiotics, even though they too may go the route of the dinosaur.
 

Using What Bacteriophage Have Learned to Develop Novel Tools for Treating Gram-positive Infections
Vincent A. Fischetti, PhD, The Rockefeller University

With mounting antibiotic resistance, new anti-infectives must be developed to remain one step ahead of pathogenic bacteria. Bacteriophages have evolved with bacteria for about a billion years. During this time phage have evolved systems that may be exploited to kill bacteria. The lytic system consists of a holin and at least one lysin capable of degrading the bacterial cell wall. Lysins act on bonds in the peptidoglycan resulting in cell lysis and release of progeny phage. While lysins have been known for decades, they have been recently used in their purified form to kill pathogenic bacteria on mucous membrane surfaces, infected tissues and in blood. Nanogram to sub-microgram quantities of purified lysin per milliliter is sufficient to sterilize a 107 bacterial suspension in seconds to minutes. To date, other than chemical agents, there is no biological compound known that can kill bacteria this quickly. Since nearly all bacteria are or can be infected by bacteriophage, such enzymes may be developed for nearly all disease-causing gram-positive bacteria. The Fischetti lab has recombinantly produced phage lysins that kill the major gram-positive pathogens—Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis, group B streptococci and Bacillus anthracis—and has used these enzymes to destroy their respective bacteria in animal models of disease. A more detailed understanding of phage lysins has revealed that the binding domain of these enzymes have evolved to target essential structures in the gram-positive cell wall. Using this information, strategies have been developed to identify novel pathways in the gram-positive organism that are targets for antibiotics with reduced potential for resistance.
 

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