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ARRA Investments in Antimicrobial (Drug) Resistance

Public Health Burden
Increasing use of antimicrobials in humans, animals, and agriculture has resulted in numerous microbes developing resistance to these powerful drugs. Consequently, many infectious diseases are increasingly difficult and costly to treat.

Mechanisms of Antimicrobial Resistance
If scientists can learn more about how microbes develop resistance, they can generate new ideas to make effective diagnostics, therapeutics, and vaccines. A variety of ARRA funded grants are supporting basic research on antimicrobial resistance.
  • One project is exploring the physiological adaptation of bacteria under antibiotic pressure, which could inform new ways of preventing the emergence and spread of resistant bacterial infections.1
  • One grant is focused on gaining greater understanding of natural bacterial resistance to antimicrobial peptides, which may help researchers predict and possibly overcome resistance to this promising new class of antibacterial therapies.2
  • Another project is investigating the mechanisms underlying development and spread of antibiotic resistance in Staphylococcus aureus, which could help establish new therapeutic targets.3
  • Another project aims to understand the molecular basis of bacterial resistance to a certain class of antimicrobial drugs and to develop strategies to defeat it.4
Molecular Epidemiology
Scientists who conduct molecular epidemiological studies focus on genetic and environmental factors to learn about the origin and spread of disease. This kind of research on antimicrobial resistance has the potential to inform infection control measures in both hospitals and community settings. Several ARRA funded grants are supporting research in molecular epidemiology.
  • One grant is supporting the surveillance of community-associated infections in the United States caused by a specific drug-resistant strain of E. coli. These bacteria may lead to treatment failures of common infections, such as urinary tract infections.5
  • Another grant is determining the scope of drug-resistant bacterial infections in pediatric patients in the United States. This study may yield information that helps doctors to better treat children with severe bacterial infections, and provide important data about resistance in Gram-negative bacteria.6
  • Another grant is investigating the genetic makeup of several penicillin-resistant strains of Streptococcus pneumoniae (Sp) that have spread around the world, to find out how similar they are to Sp strains that are vulnerable to vaccines.7
While waiting to receive their patients’ test results, healthcare providers often prescribe broad-spectrum antimicrobials or antibiotics to which the infection is resistant when more specific treatments might be more effective. This practice is a factor in the emergence of antimicrobial resistance. To improve treatment and reduce resistance, NIH ARRA funds support the development of improved diagnostic tools.
  • One study aims to develop a fast and reliable diagnostic test for Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common hospital-acquired infections.8
  • Another project is investigating a novel technique for rapid detection of bacteria’s susceptibility to antibiotics, so that doctors can prescribe effective medications.9
The rapid evolution of antimicrobial resistance necessitates the discovery of new drugs, as well as strategies to preserve the effectiveness of existing drugs.  ARRA funded awards are supporting research to develop new therapeutics and to improve our understanding of microbes’ interactions with drugs.
  • Several studies aim to combat MRSA, one through the discovery of new classes of antimicrobial compounds,10 and another through investigation of a promising anti-MRSA substance.11
  • Echinocandins are antifungal drugs that inhibit cell wall synthesis. One study will investigate mutations that lead some fungal species to develop resistance to these drugs.12
  • Another project seeks to understand how the fungus Candida albicans develops resistance to a class of antifungal drugs called azoles.13
  • Another study will determine how genetic changes in Aspergillus fungus lead to drug resistance, laying the foundation for discovery of new antifungal drugs.14
  • One grant proposes a comprehensive framework for studying the genetic basis of resistance across diverse drug classes, a study which may lead to new methods for combating resistance.15
  • One project will investigate bacterial enzymes that destroy certain antibiotics and may lead to new directions in future antibiotic design.16

  1. 1R21AI081101-01 -- Antibiotic Pressure and Selection of TCA Cycle Mutants in Staphylococcus epidermi -- Fey, Paul D (NE)
  2. 1R21AI076678-01 -- Genetic Determinants of Antimicrobial Peptide Resistance in Gram-negative Bacteria -- Lee, Hyunwoo (IL)
  3. 1P01AI083214-01 -- Harvard-wide Program on Antibiotic Resistance -- Gilmore, Michael S (MA)
  4. 2R56AI060841-06 -- Mechanisms of Resistance in Gram-Negative Bacteria -- Sousa, Marcelo Carlos (CO)
  5. 1R03AI079296-01A1 -- Epidemiology of Community-Associated, ESBL-Producing Escherichia coli -- Doi, Yohei (PA)
  6. 1R56AI083413-01 -- National Surveillance of Emerging MDR in Pediatric Enterobacteriaceae Infections -- Zerr, Danielle M (WA)
  7. 1R01AI080935-01A1 -- Impact of Antibiotics and Vaccines on the in vivo Evolution of S. pneumoniae -- Ehrlich, Garth D (PA)
  8. 1R03AI083939-01 -- Rapid Novel Molecular Detection of Methicillin-Resistant Staphylococcus aureus -- Usacheva, Elena Anatolievna (IL)
  9. 1R21AI079474-01A1 -- Novel Methodology for Rapid Antibiotic Susceptibility Testing in S. aureus -- Sauer-Budge, Alexis F (MA)
  10. 1F32AI084316-01 -- Discovery of Small Molecules that Restore Methicillin Sensitivity to MRSA -- O’Neill, Jennifer Campbell (MA)
  11. 1R21AI081025-01 -- MRSA activity of a Bacillus pumilus natural isolate -- Nakano, Michiko M (OR)
  12. 1R01AI075272-01A2 -- Mutational Analysis of Fks1: Intrinsic Echinocandin Resistance -- Edlind, Thomas D (PA)
  13. 2R01AI058145-04A1 -- Novel Azole Resistance Mechanisms in Candida albicans -- Rogers, P. David (TN)
  14. 1R01AI074673-01A1 -- Echinocandin Resistance in Aspergillus -- May, Gregory S (TX)
  15. 1R56AI077562-01A1 -- Comprehensive genetic characterization of antibiotic resistance -- Tavazoie, Saeed F (NJ)
  16. 2R01AI017986-27A2 -- Beta-Lactamases and DD-Peptidases: Active Site Chemistry -- Pratt, Rex F (CT)

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