Antimicrobial (Drug) Resistance Research in NIAID Labs
NIAID laboratories are at the forefront of basic, translational, and clinical research on antimicrobial resistance. Focusing on emerging public health threats such as drug-resistant staph, tuberculosis, and malaria, NIAID researchers seek to understand the fundamental causes of resistance—from organism and disease progression studies to research on the advantages and shortcomings of current antibiotics.
Frank R. DeLeo, Ph.D., and Michael Otto, Ph.D.
LHBP scientists are studying the interaction of staphylococci bacteria with the immune system. They are especially interested in understanding how staphylococci evade bacteria-killing cells so that they can find targets for the development of new therapies to treat drug-resistant staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA) and community-associated MRSA.
Another area of study in LHBP is the formation of biofilms by staphylococci. In the hospital setting, S. epidermidis is a major cause of difficult-to-treat infections associated with catheters, which promote the formation of bacteria-laden biofilms on the catheter surface. These slippery films provide a protective matrix that hides the bacterial colonies from both the immune system and from antimicrobial drugs. The scientists hypothesize that drugs targeting biofilm formation will be of extraordinary use in anti-staphylococcal therapy by enabling the immune system to fight infection and increasing the efficiency of common antibiotics.
Clifton E. Barry, III, Ph.D.
LCID has a substantial program to develop new drugs that dramatically shorten the time necessary to complete effective tuberculosis (TB) therapy. New drugs are desperately needed to address the problem of TB drug resistance, and NIAID scientists have been instrumental in the development of two (SQ-109 and PA-824) of the seven novel compounds currently in clinical development [ref: JID 15 August 2007 (vol 196 no S1, p. 28)].
LCID also aims to gain further understanding of the underlying reasons for the development of drug resistance. Several years ago, scientists from LCID began working with colleagues from Africa and Asia on the problem of multidrug resistant (MDR) TB, and this work has evolved to investigations of extensively drug resistant (XDR) TB.
In 2006, NIAID researchers and South Korean collaborators opened a clinical study at the Masan National Tuberculosis Hospital in South Korea for MDR TB patients. Masan Hospital is the national referral center for TB treatment failures in South Korea with the largest population of inpatient MDR TB patients anywhere in the world. Several hundred volunteers have enrolled and are being studied in an effort to understand the development of MDR TB. This group is also providing our first insight into a large cohort of XDR TB patients.
Thomas E. Wellems, M.D., Ph.D.
Drug resistance of malaria parasites and the factors that affect clinical outcomes after antimalarial treatment are the focus of intense study in LMVR. Researchers are characterizing molecules that determine chloroquine and quinine responses in plasmodium parasites with a view toward new therapeutic strategies and diagnostics for the detection of drug-resistant malaria. NIAID researchers are also exploiting malaria parasite genome databases to study the mechanism of drug resistance and have identified candidate genes that may be involved in parasite resistance to various drugs.
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