Heteroresistance is a phenotype in which a bacterial isolate contains sub-populations of cells with increased antibiotic resistance when compared with the susceptible main population.[1] This phenomenon is known to be highly prevalent among several antibiotic classes and bacterial isolates and associated with treatment failure through the enrichment of low frequencies of resistant subpopulations in the presence of antibiotics.[2] Heteroresistance is known to be highly unstable, meaning that the resistance sub-population can revert to susceptibility within a limited number of generations of growth in the absence of antibiotic.[2] Regarding the instability and the transient characteristic of heteroresistance subpopulations, the detection of this subpopulation often face difficulties by the conventional minimum inhibitory concentration methods.[3] Hence, there is a significant demand for clinical microbiology laboratories to use rapid standardized methods to identify heteroresistance in pathologic specimen to prescribe a proper antibiotic treatment for patients.

Mechanisms

The enrichment of resistance sub-populations can be due to the acquisition of resistant mutations that are genetically stable but have high fitness cost or due to the enrichment of sub-population with increased copy number of resistance-conferring tandem gene amplifications.[4][1]

References

  1. 1 2 Andersson, Dan I.; Nicoloff, Hervé; Hjort, Karin (August 2019). "Mechanisms and clinical relevance of bacterial heteroresistance". Nature Reviews Microbiology. 17 (8): 479–496. doi:10.1038/s41579-019-0218-1. ISSN 1740-1534. PMID 31235888. S2CID 195329648.
  2. 1 2 El-Halfawy, Omar M.; Valvano, Miguel A. (January 2015). "Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity". Clinical Microbiology Reviews. 28 (1): 191–207. doi:10.1128/CMR.00058-14. ISSN 0893-8512. PMC 4284305. PMID 25567227.
  3. ↑ Hjort, Karin; Nicoloff, Hervé; Andersson, Dan I (October 2016). "Unstable tandem gene amplification generates heteroresistance (variation in resistance within a population) to colistin in Salmonella enterica". Molecular Microbiology. 102 (2): 274–289. doi:10.1111/mmi.13459. ISSN 0950-382X. PMID 27381382.
  4. ↑ Nicoloff, Hervé; Hjort, Karin; Levin, Bruce R.; Andersson, Dan I. (March 2019). "The high prevalence of antibiotic heteroresistance in pathogenic bacteria is mainly caused by gene amplification". Nature Microbiology. 4 (3): 504–514. doi:10.1038/s41564-018-0342-0. ISSN 2058-5276. PMID 30742072. S2CID 59945259.
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