Antibiotic Tolerance and Persistence Studied Throughout Bacterial Growth Phases

Maffei, Enea; Fino, Cinzia; Harms, Alexander

doi:10.1007/978-1-0716-1621-5_2

Cited by 6 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are stably dormant without loss of cell viability and are non-dividing because we do not observe significant killing even under prolonged treatment with lethal concentrations of β-lactam drugs that poison bacterial cell wall biosynthesis, eliminating any intermittently growing cell (Fig. 2b) 35,58 . This is different from other methodologies sometimes used in the field.…”

Section: Discussionmentioning

confidence: 89%

“…1 and Extended Data Fig. 1) 35 , we hypothesized that the bacterial core signalling orchestrating their dormant physiology might be responsible for both phenomena. In many Gram-negatives, the stringent response second messenger (p)ppGpp and stress response sigma factor RpoS together tune down cellular processes in stationary phase which is thought to cause antibiotic tolerance 9,50-52 .…”

Section: Resultsmentioning

confidence: 99%

“…We therefore adapted our previously developed bacteriophage isolation setup 35 to broadly screen for new phages that could directly replicate on dormant hosts by using deep-dormant cultures of E. coli or P. aeruginosa as bait (Fig. 2a).…”

Section: Resultsmentioning

confidence: 99%

“…However, we failed to observe an ability of phages T7 and UT1 to replicate on stationary phase cells that had been reported previously 31,32 . It seems likely to us that this difference is due to differences in the “stationary phase” physiology of the bacteria that have been investigated because the cells in our assay setup might be particularly dormant as evidenced, e.g., by their strong antibiotic tolerance 35 . Notably, phage T7 has previously been reported to be highly proficient at infecting highly starved and stressed (albeit growing) cells 61 , making it plausible that this phage may be able to replicate on non-growing cells at a less dormant stage of stationary phase.…”

Section: Discussionmentioning

confidence: 99%

“…LB agar plates were prepared by supplementing LB medium with agar at 1.5% w/v before autoclaving. M9Glc was prepared as described previously 35 . The M9Rich culture medium was conceived as a variant of regular M9Glc medium supplemented with 10% v/v LB medium (prepared without NaCl) to promote the growth of diverse strains 35 .…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Phage Paride hijacks bacterial stress responses to kill dormant, antibiotic-tolerant cells

Maffei

Burkolter

Heyer

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Bacteriophages are fierce viral predators with no regard for pathogenicity or antibiotic resistance of their bacterial hosts. Despite early recognition of their therapeutic potential and the current escalation of bacterial multidrug resistance, phages have so far failed to become a regular treatment option in clinical practice. One reason is the occasional discrepancy between poor performance of selected phages in vivo despite high potency in vitro. Similar resilience of supposedly drug-sensitive bacterial infections to antibiotic treatment has been linked to persistence of dormant cells inside patients. Given the abundance of non-growing bacteria also in the environment, we wondered whether some phages can infect and kill these antibiotic-tolerant cells. As shown previously, most phages failed to replicate on dormant hosts and instead entered a state of hibernation or pseudolysogeny. However, we isolated a new Pseudomonas aeruginosa phage named Paride with the exciting ability to directly kill dormant, antibiotic-tolerant hosts by lytic replication, causing sterilization of deep-dormant cultures in synergy with the β-lactam meropenem. Intriguingly, efficient replication of Paride on dormant hosts depends on the same bacterial stress responses that also drive antibiotic tolerance. We therefore suggest that Paride hijacks weak spots in the dormant physiology of antibiotic-tolerant bacteria that could be exploited as Achilles′ heels for the development of new treatments targeting resilient bacterial infections.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Phage Paride hijacks bacterial stress responses to kill dormant, antibiotic-tolerant cells

Maffei

Burkolter

Heyer

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Bacterial proton motive force as an unprecedented target to control antimicrobial resistance

Yang

Tong

Shi

et al. 2023

Medicinal Research Reviews

View full text Add to dashboard Cite

Novel antibacterial therapies are urgently required to tackle the increasing number of multidrug‐resistant pathogens. Identification of new antimicrobial targets is critical to avoid possible cross‐resistance issues. Bacterial proton motive force (PMF), an energetic pathway located on the bacterial membrane, crucially regulates various biological possesses such as adenosine triphosphate synthesis, active transport of molecules, and rotation of bacterial flagella. Nevertheless, the potential of bacterial PMF as an antibacterial target remains largely unexplored. The PMF generally comprises electric potential (ΔΨ) and transmembrane proton gradient (ΔpH). In this review, we present an overview of bacterial PMF, including its functions and characterizations, highlighting the representative antimicrobial agents that specifically target either ΔΨ or ΔpH. At the same time, we also discuss the adjuvant potential of bacterial PMF‐targeting compounds. Lastly, we highlight the value of PMF disruptors in preventing the transmission of antibiotic resistance genes. These findings suggest that bacterial PMF represents an unprecedented target, providing a comprehensive approach to controlling antimicrobial resistance.

show abstract

Relative fitness of wild-type and phage-resistant pyomelanogenic P. aeruginosa and effects of combinatorial therapy on resistant formation

Mary,

Kalangadan,

Prakash

et al. 2024

Heliyon

View full text Add to dashboard Cite

Antibiotic Tolerance and Persistence Studied Throughout Bacterial Growth Phases

Cited by 6 publications

References 28 publications

Phage Paride hijacks bacterial stress responses to kill dormant, antibiotic-tolerant cells

Phage Paride hijacks bacterial stress responses to kill dormant, antibiotic-tolerant cells

Bacterial proton motive force as an unprecedented target to control antimicrobial resistance

Relative fitness of wild-type and phage-resistant pyomelanogenic P. aeruginosa and effects of combinatorial therapy on resistant formation

Contact Info

Product

Resources

About