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 Staphylococcus aureus, tuberculosis, and malaria, NIAID researchers seek to understand the fundamental causes of resistance. Novel investigations are currently being conducted, including those on the basic biology of the organism and disease progression studies as well as the advantages and shortcomings of current antibiotics.

Laboratory of Bacteriology (LB)

Frank R. DeLeo, Ph.D., and Michael Otto, Ph.D.

LB scientists study antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae—causes of human infections. Ongoing research includes investigation of the interaction of S. aureus with the immune system, especially how these bacteria evade killing by white blood cells. Insights in this area of research will help identify targets for developing new therapies to treat drug-resistant bacteria. Another area of study in LB 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. Slippery, bacteria-laden biofilms form on the catheter surface itself, providing a protective matrix that hides the bacterial colonies from both the immune system and from antimicrobial drugs. Scientists hypothesize that drugs preventing biofilm formation will be extremely useful in anti-staphylococcal therapy by enabling the immune system to fight infection and increasing the effectiveness of common antibiotics.

Laboratory of Clinical Immunology and Microbiology  (LCIM)

Clifton E. Barry III, Ph.D.

LCIM is working to develop new drugs that dramatically shorten the time needed to treat tuberculosis (TB). New drugs are desperately needed to address the problem of TB drug resistance, and NIAID scientists have helped advance two (SQ-109 and PA-824) of the seven novel compounds currently in clinical development.

LCIM also aims to further understand the underlying reasons for the development of drug resistance. Several years ago, scientists from LCIM 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 in the clinical study. Studies such as these are helping investigators to understand the development of MDR TB. This group is also providing the first insight into a large cohort of XDR TB patients.

Laboratory of Malaria and Vector Research (LMVR)

Thomas E. Wellems, M.D., Ph.D.

LMVR conducts extensive research on drug resistance in malaria-causing Plasmodium parasites and factors that affect health outcomes after treatment with antimalarial drugs. LMVR scientists are studying molecules that determine how Plasmodium parasites respond to the antimalarial drugs chloroquine and quinine. This research may lead to new therapeutic strategies and diagnostics for detecting drug-resistant malaria. NIAID researchers are also reviewing data on the malaria parasite genome and have identified candidate genes that may be involved in the parasite’s resistance to various drugs.

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