Are all antibiotic persisters created equal?

Shultis, Michael W.; Mulholland, Claire V.; Berney, Michael

doi:10.3389/fcimb.2022.933458

Cited by 20Bacterial Genetics and BiotechnologyTuberculosis Research and EpidemiologyAntimicrobial Resistance in Staphylococcus

Are all antibiotic persisters created equal?

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Shultis, Michael W., Mulholland, Claire V., Berney, Michael·2022·Frontiers in Cellular and Infection Microbiology

DOI 10.3389/fcimb.2022.933458PMC PMC9428696

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Abstract

Antibiotic persisters are a sub-population of bacteria able to survive in the presence of bactericidal antibiotic despite the lack of heritable drug resistance mechanisms. This phenomenon exists across many bacterial species and is observed for many different antibiotics. Though these bacteria are often described as “multidrug persisters” very few experiments have been carried out to determine the homogeneity of a persister population to different drugs. Further, there is much debate in the field as to the origins of a persister cell. Is it formed spontaneously? Does it form in response to stress? These questions are particularly pressing in the field of Mycobacterium tuberculosis, where persisters may play a crucial role in the required length of treatment and the development of multidrug resistant organisms. Here we aim to interpret the known mechanisms of antibiotic persistence and how they may relate to improving treatments for M. tuberculosis, exposing the gaps in knowledge that prevent us from answering the question: Are all antibiotic persisters created equal?

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Fungal persisters are often recalcitrant to multiple antibiotics, as has been observed in antibiotic persistence.
“In antibiotic persistence, persisters are often recalcitrant to multiple antibiotics [49,50], which has been observed with fungal persisters as well.”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [50]
The “Multidrug persistence” section reports bacterial persister populations that tolerate some antibiotic combinations and show cross-tolerance to certain other drugs. It also says cross-tolerance varies by drug and cautions that finding persisters after separate drug treatments does not establish that the same persisters tolerate multiple antibiotics. The source therefore supports the possibility, but not the unqualified frequency implied by “often.” The citation is attached to the antibiotic-persistence clause, not the statement about fungal persisters. (LLM, conf=0.82)
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Serum concentrations of rifampicin and isoniazid in tuberculosis.
Seth, V., Beotra, A., Seth, S. D. S., Semwal, O. P., Kabra, S. K., Jain, Y. K., & Mukhopadhya, S. (1993) · PubMed · Cited by 26 · see citing works
The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity?
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Prach, L. M., Pascopella, L., Barry, P. M., Flood, J., Porco, T. C., Hopewell, P. C., & Metcalfe, J. Z. (2013) · AIDS · doi:10.1097/01.aids.0000432445.07437.07 · Cited by 16 · see citing works
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Antibiotic tolerance: targeting bacterial survival
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Additional file 1 of Effects of antibiotic cocktail on the fecal microbiota and their potential correlation of local immune response
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Caractérisatiοn du lipidοme et de la physiοlοgie de cellules persisters à la ciprοflοxacine d'Acinetοbacter baumannii.
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Self-citation
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Mihnev, A., Luong, D., Porat, J., & Chang, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.23.761362

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Authors: Shultis, M. W., Mulholland, C. V., & Berney, M.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Berney, Michael
ORCID: Mulholland, Claire V.
Berney, Michael
Venue: Frontiers in Cellular and Infection Microbiology
Publisher: Frontiers Media SA
Published: 2022-08-17
Volume: 12
Pages: 933458-933458
ISSN: 2235-2988 (ISSN-L)
DOI: 10.3389/fcimb.2022.933458
PMC: PMC9428696
OpenAlex: W4292317564
Cited by: 19
References: 95
Citations by year: 2026: 4 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 1
FWCI: 0.58
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Potts Memorial Foundation
National Institute of Allergy and Infectious Diseases
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Keywords: Mycobacterium tuberculosis, antibiotic tolerance, multidrug resistance, stress response, tuberculosis treatment duration
MeSH terms: Anti-Bacterial Agents, Mycobacterium tuberculosis

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