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, particularly and , are responsible for many hospital-acquired infections. With their intrinsic antibiotic resistance and ability to form biofilms, enterococcal infections are already challenging to manage. However, when heterogenous populations are present, such as those exhibiting heteroresistance and persistence, the complexity of these infections increases exponentially not only due to their treatment but also due to their difficult diagnosis. In this study, we provide a summary of the current understanding of both heteroresistance and persistence in terms of mechanisms, diagnosis and treatment and subsequently review recent literature pertaining to these susceptibility types specifically in enterococci.
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http://dx.doi.org/10.1080/17460913.2024.2393003 | DOI Listing |
Unlabelled: Rising rates of antibiotic treatment failure highlight the complexity of resistance mechanisms. While conventional, genetically encoded resistance is well established, recent studies have uncovered widespread non-canonical mechanisms driven by phenotypically insensitive subpopulations hiding in seemingly susceptible populations, such as heteroresistance, persistence or adaptive resistance. These variants are not only clinically significant but also act as evolutionary precursors to fully resistant populations, rendering infections increasingly difficult to control.
View Article and Find Full Text PDFmSystems
June 2025
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Heteroresistance and persistence are examples of mechanisms that can allow otherwise drug-susceptible bacteria to survive and resume growth after antibiotic exposure. These temporary forms of antibiotic tolerance can be caused by the upregulation of stress response genes or a decrease in cell growth rate. However, it is not clear how the expression of multiple genes contributes to tolerance phenotypes.
View Article and Find Full Text PDFmSphere
May 2025
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
is a significant public health threat due to its environmental persistence and multidrug resistance, with echinocandins being the preferred treatment. However, in addition to resistance, echinocandin tolerance and heteroresistance may contribute to treatment challenges. Echinocandin tolerance involves reduced drug-mediated killing, while heteroresistance is the ability of a small cell subset to grow at high drug concentrations.
View Article and Find Full Text PDFMicrobiol Spectr
April 2025
Department of Biology, Emory University, Atlanta, Georgia, USA.
Unlabelled: The rational design of the antibiotic treatment of bacterial infections employs these drugs to reach concentrations that exceed the minimum needed to prevent the replication of the target bacteria. However, within a treated patient, spatial and physiological heterogeneity promotes antibiotic gradients such that the concentration of antibiotics at specific sites is below the minimum needed to inhibit bacterial growth. Here, we investigate the effects of sub-inhibitory antibiotic concentrations on three parameters central to bacterial infection and the success of antibiotic treatment, using experiments with and mathematical and computer-simulation models.
View Article and Find Full Text PDFJ Fungi (Basel)
February 2025
Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing 100730, China.
Antifungal resistance poses a critical global health threat, particularly in immuno-compromised patients. Beyond the traditional resistance mechanisms rooted in heritable and stable mutations, a distinct phenomenon known as heteroresistance has been identified, wherein a minority of resistant fungal cells coexist within a predominantly susceptible population. Heteroresistance may be induced by pharmacological factors or non-pharmacological agents.
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