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Heteroresistance: A Harbinger of Future Resistance

  • Karl Drlica
  • Bo Shopsin
  • Xilin Zhao
Chapter
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

Abstract

During infection, bacterial populations often contain subpopulations that exhibit reduced antimicrobial susceptibility. The resulting population heterogeneity is called heteroresistance. Since a heteroresistant population can evolve into a resistant one, a heteroresistant infection is a risk factor for the development of complete resistance. We describe heteroresistant tuberculosis as an example of a chronic infection in which enrichment of resistant subpopulations readily progresses in individual patients and threatens successful treatment. Heteroresistance provides such a clear warning that improved DNA-based tests are being designed to identify isolates containing resistant subpopulations while they are still small. We also examine heteroresistance with Staphylococcus aureus as an example of how resistant subpopulations affect treatment of an opportunistic pathogen. Heteroresistance to methicillin resistance emerged via a horizontal gene transfer event that produced methicillin-resistant S. aureus (MRSA), which spread worldwide. Now heteroresistance to vancomycin-intermediate Staphylococcus aureus (VISA) is appearing among MRSA strains. Many other pathogens are also displaying heteroresistance that is often undetected by routine, automated susceptibility testing. Refinement of assays is likely to reveal that antimicrobial heteroresistance is much more prevalent than we realize and that treatment strategies need to be refined now to slow the emergence of new resistance.

Notes

Acknowledgments

We thank the following for helpful discussions and critical comments: Veronique Dartois, Dorothy Fallows, Marila Gennaro, Ben Gold, Barry Kreiswirth, Richard Pine, and George Zhanel. The authors’ work was supported by NIH grants 1DP20D007423, 1R01AI073491, 1R21A03781, and 1R01AI87671.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Public Health Research InstituteNew Jersey Medical School, Rutgers Biomedical and Health SciencesNewarkUSA
  2. 2.Departments of Medicine and MicrobiologyNew York University School of MedicineNew YorkUSA
  3. 3.Department of Microbiology, Biochemistry, & Molecular GeneticsNew Jersey Medical School, Rutgers Biomedical and Health SciencesNewarkUSA
  4. 4.State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsSchool of Public Health, Xiamen UniversityXiamenChina

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