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Microorganisms
Special Issues
Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence
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Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 16049

Special Issue Editors

Dr. Mehmet A. Orman

E-Mail Website
Guest Editor
William A. Brookshire Department of Chemical and Biomolecular Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USA
Interests: infectious diseases; persisters; antipersister therapeutics; persister metabolism; persister cell resuscitation; bacterial autophagy; cancer persister
Dr. Wendy W.K. Mok

E-Mail Website
Guest Editor
Department of Molecular Biology & Biophysics, UCONN Health, Farmington, CT 06030-3305, USA
Interests: antibiotic persistence; antibiotic resistance; persister resuscitation; microbial interactions; drug discovery

Special Issue Information

Dear Colleagues,

Antibiotic treatment failure is a global public health crisis and imposes a grave impact on many developing countries. In addition to resistant mutants, antibiotics can fail against microorganisms that survive therapy without acquiring heritable genetic changes that enable them to grow in the presence of inhibitory antibiotic concentrations. Bacterial persisters, which are reversible antibiotic-tolerant cells within clonal cultures, contribute to this problem because persister cells are thought to facilitate the recurrence of chronic and biofilm-related infections. Although persister cells transiently survive lethal concentrations of antibiotics, they have been shown to promote the emergence of drug resistant mutants. The persistence phenomenon has been documented across multiple microbial organisms and in response to a variety of antibiotic classes.

Persistence can be induced stochastically due to random fluctuations in levels of stress-related cellular molecules. Deterministic mechanisms triggered by environmental signals, such as antibiotic treatment, nutrient depletion, and osmotic conditions, can also affect the level of persister cells present in the population. Following antibiotic treatment, persister cells can potentially regain the ability to initiate cell growth in response to environmental cues and establish populations of antibiotic-sensitive cells. Given that mechanisms associated with persister cell formation, survival and resuscitation are highly complex and diverse, many aspects of persistence are yet to be discovered. Therefore, we would like to invite you to send contributions to this Special Issue of Microorganisms. Topics of particular interest in this issue include, but are not limited to, recent approaches and findings in persister formation and resuscitation mechanisms; the links between persistence and mutational resistance mechanisms; persister cell heterogeneity; persister cell physiology; and anti-persister strategies.

Dr. Mehmet A. Orman
Dr. Wendy W.K. Mok
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bacterial persisters
  • phenotypic heterogeneity
  • persister formation
  • survival and resuscitation mechanisms
  • links between persistence and resistance
  • persister cell physiology
  • environmental triggers of persistence

Published Papers (4 papers)

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Research

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13 pages, 1718 KiB  
Article
Fluoroquinolone Persistence in Escherichia coli Requires DNA Repair despite Differing between Starving Populations
by Annabel S. Lemma, Nashaly Soto-Echevarria and Mark P. Brynildsen
Microorganisms 2022, 10(2), 286; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10020286 - 26 Jan 2022
Cited by 2 | Viewed by 2677
Abstract
When faced with nutritional deprivation, bacteria undergo a range of metabolic, regulatory, and biosynthetic changes. Those adjustments, which can be specific or independent of the missing nutrient, often alter bacterial tolerance to antibiotics. Here, using fluoroquinolones, we quantified Escherichia coli persister levels in [...] Read more.
When faced with nutritional deprivation, bacteria undergo a range of metabolic, regulatory, and biosynthetic changes. Those adjustments, which can be specific or independent of the missing nutrient, often alter bacterial tolerance to antibiotics. Here, using fluoroquinolones, we quantified Escherichia coli persister levels in cultures experiencing starvation from a lack of carbon (C), nitrogen (N), phosphorous (P), or magnesium (Mg2+). Interestingly, persister levels varied significantly based on the type of starvation as well as fluoroquinolone used with N-starved populations exhibiting the highest persistence to levofloxacin, and P-starved populations exhibiting the highest persistence to moxifloxacin. However, regardless of the type of starvation or fluoroquinolone used, DNA repair was required by persisters, with ∆recA and ∆recB uniformly exhibiting the lowest persistence of the mutants assayed. These results suggest that while the type of starvation and fluoroquinolone will modulate the level of persistence, the importance of homologous recombination is consistently observed, which provides further support for efforts to target homologous recombination for anti-persister purposes. Full article
(This article belongs to the Special Issue Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence)
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20 pages, 3074 KiB  
Article
Bugs on Drugs: A Drosophila melanogaster Gut Model to Study In Vivo Antibiotic Tolerance of E. coli
by Bram Van den Bergh
Microorganisms 2022, 10(1), 119; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010119 - 07 Jan 2022
Cited by 3 | Viewed by 3283
Abstract
With an antibiotic crisis upon us, we need to boost antibiotic development and improve antibiotics’ efficacy. Crucial is knowing how to efficiently kill bacteria, especially in more complex in vivo conditions. Indeed, many bacteria harbor antibiotic-tolerant persisters, variants that survive exposure to our [...] Read more.
With an antibiotic crisis upon us, we need to boost antibiotic development and improve antibiotics’ efficacy. Crucial is knowing how to efficiently kill bacteria, especially in more complex in vivo conditions. Indeed, many bacteria harbor antibiotic-tolerant persisters, variants that survive exposure to our most potent antibiotics and catalyze resistance development. However, persistence is often only studied in vitro as we lack flexible in vivo models. Here, I explored the potential of using Drosophila melanogaster as a model for antimicrobial research, combining methods in Drosophila with microbiology techniques: assessing fly development and feeding, generating germ-free or bacteria-associated Drosophila and in situ microscopy. Adult flies tolerate antibiotics at high doses, although germ-free larvae show impaired development. Orally presented E. coli associates with Drosophila and mostly resides in the crop. E. coli shows an overall high antibiotic tolerance in vivo potentially resulting from heterogeneity in growth rates. The hipA7 high-persistence mutant displays an increased antibiotic survival while the expected low persistence of ΔrelAΔspoT and ΔrpoS mutants cannot be confirmed in vivo. In conclusion, a Drosophila model for in vivo antibiotic tolerance research shows high potential and offers a flexible system to test findings from in vitro assays in a broader, more complex condition. Full article
(This article belongs to the Special Issue Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence)
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Review

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22 pages, 4634 KiB  
Review
Single-Cell Technologies to Study Phenotypic Heterogeneity and Bacterial Persisters
by Patricia J. Hare, Travis J. LaGree, Brandon A. Byrd, Angela M. DeMarco and Wendy W. K. Mok
Microorganisms 2021, 9(11), 2277; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9112277 - 01 Nov 2021
Cited by 12 | Viewed by 5508
Abstract
Antibiotic persistence is a phenomenon in which rare cells of a clonal bacterial population can survive antibiotic doses that kill their kin, even though the entire population is genetically susceptible. With antibiotic treatment failure on the rise, there is growing interest in understanding [...] Read more.
Antibiotic persistence is a phenomenon in which rare cells of a clonal bacterial population can survive antibiotic doses that kill their kin, even though the entire population is genetically susceptible. With antibiotic treatment failure on the rise, there is growing interest in understanding the molecular mechanisms underlying bacterial phenotypic heterogeneity and antibiotic persistence. However, elucidating these rare cell states can be technically challenging. The advent of single-cell techniques has enabled us to observe and quantitatively investigate individual cells in complex, phenotypically heterogeneous populations. In this review, we will discuss current technologies for studying persister phenotypes, including fluorescent tags and biosensors used to elucidate cellular processes; advances in flow cytometry, mass spectrometry, Raman spectroscopy, and microfluidics that contribute high-throughput and high-content information; and next-generation sequencing for powerful insights into genetic and transcriptomic programs. We will further discuss existing knowledge gaps, cutting-edge technologies that can address them, and how advances in single-cell microbiology can potentially improve infectious disease treatment outcomes. Full article
(This article belongs to the Special Issue Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence)
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23 pages, 981 KiB  
Review
Cellular Self-Digestion and Persistence in Bacteria
by Sayed Golam Mohiuddin, Sreyashi Ghosh, Han G. Ngo, Shayne Sensenbach, Prashant Karki, Narendra K. Dewangan, Vahideh Angardi and Mehmet A. Orman
Microorganisms 2021, 9(11), 2269; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9112269 - 31 Oct 2021
Cited by 4 | Viewed by 3652
Abstract
Cellular self-digestion is an evolutionarily conserved process occurring in prokaryotic cells that enables survival under stressful conditions by recycling essential energy molecules. Self-digestion, which is triggered by extracellular stress conditions, such as nutrient depletion and overpopulation, induces degradation of intracellular components. This self-inflicted [...] Read more.
Cellular self-digestion is an evolutionarily conserved process occurring in prokaryotic cells that enables survival under stressful conditions by recycling essential energy molecules. Self-digestion, which is triggered by extracellular stress conditions, such as nutrient depletion and overpopulation, induces degradation of intracellular components. This self-inflicted damage renders the bacterium less fit to produce building blocks and resume growth upon exposure to fresh nutrients. However, self-digestion may also provide temporary protection from antibiotics until the self-digestion-mediated damage is repaired. In fact, many persistence mechanisms identified to date may be directly or indirectly related to self-digestion, as these processes are also mediated by many degradative enzymes, including proteases and ribonucleases (RNases). In this review article, we will discuss the potential roles of self-digestion in bacterial persistence. Full article
(This article belongs to the Special Issue Novel Approaches for Investigating Antibiotic Resistance and Bacterial Persistence)
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