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Heteroresistance: A Harbinger of Future Resistance

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Antimicrobial Resistance in the 21st Century

Part of the book series: Emerging Infectious Diseases of the 21st Century ((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.

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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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Authors and Affiliations

  1. Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA

    Karl Drlica & Xilin Zhao

  2. Departments of Medicine and Microbiology, New York University School of Medicine, New York, NY, USA

    Bo Shopsin

  3. Department of Microbiology, Biochemistry, & Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA

    Xilin Zhao

  4. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian Province, China

    Xilin Zhao

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  1. Karl Drlica
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Correspondence to Karl Drlica .

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  1. Department of Medicine, University of Toronto, Toronto, ON, Canada

    I. W. Fong

  2. Anti-infectives Consulting, LLC, Stonington, CT, USA

    David Shlaes

  3. Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ, USA

    Karl Drlica

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Drlica, K., Shopsin, B., Zhao, X. (2018). Heteroresistance: A Harbinger of Future Resistance. In: Fong, I., Shlaes, D., Drlica, K. (eds) Antimicrobial Resistance in the 21st Century. Emerging Infectious Diseases of the 21st Century. Springer, Cham. https://doi.org/10.1007/978-3-319-78538-7_9

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