The Eagle Effect and Antibiotic-Induced Persistence: Two Sides of the Same Coin?

Prasetyoputri, Anggia; Jarrad, Angie M.; Cooper, Matthew A.; Blaskovich, Mark A. T.

doi:10.1016/j.tim.2018.10.007

Cited by 53 publications

(55 citation statements)

References 131 publications

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“…Unexpected growth can also be observed at antibiotic concentrations above their inhibitory concentrations—MIC—in what has been known as paradoxical growth or the Eagle effect [ 125 , 154 ] and seen here in three of the four antibiotics most used in time–kill experiments ( Figure 9 ). The exposure to the two fluoroquinolones ciprofloxacin and ofloxacin, and the aminoglycoside gentamicin produce an increasing number of persisters above 0.15, 0.5, and 0.75 µg/mL, respectively.…”

Section: Discussionmentioning

confidence: 77%

“…In the light of these findings, it is logical to include as a prerequisite the optimal concentration of antibiotic for a persister assay so the survivors are not an overestimation and ultimately not an unprincipled reflection of persistence. This is particularly so since the relation between persistence to antibiotics and the Eagle effect is unknown, although there have been attempts to draw similarities [ 154 ].…”

Section: Discussionmentioning

confidence: 99%

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A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

Salcedo-Sora

Kell

2020

Antibiotics

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Background: Bacterial persistence to antibiotics relates to the phenotypic ability to survive lethal concentrations of otherwise bactericidal antibiotics. The quantitative nature of the time–kill assay, which is the sector’s standard for the study of antibiotic bacterial persistence, is an invaluable asset for global, unbiased, and cross-species analyses. Methods: We compiled the results of antibiotic persistence from antibiotic-sensitive bacteria during planktonic growth. The data were extracted from a sample of 187 publications over the last 50 years. The antibiotics used in this compilation were also compared in terms of structural similarity to fluorescent molecules known to accumulate in Escherichia coli. Results: We reviewed in detail data from 54 antibiotics and 36 bacterial species. Persistence varies widely as a function of the type of antibiotic (membrane-active antibiotics admit the fewest), the nature of the growth phase and medium (persistence is less common in exponential phase and rich media), and the Gram staining of the target organism (persistence is more common in Gram positives). Some antibiotics bear strong structural similarity to fluorophores known to be taken up by E. coli, potentially allowing competitive assays. Some antibiotics also, paradoxically, seem to allow more persisters at higher antibiotic concentrations. Conclusions: We consolidated an actionable knowledge base to support a rational development of antipersister antimicrobials. Persistence is seen as a step on the pathway to antimicrobial resistance, and we found no organisms that failed to exhibit it. Novel antibiotics need to have antipersister activity. Discovery strategies should include persister-specific approaches that could find antibiotics that preferably target the membrane structure and permeability of slow-growing cells.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

Salcedo-Sora

Kell

2020

Antibiotics

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“…The mechanism behind this seemingly-paradoxical growth is various and poorly understood. 19 Currently, we can conclude that AM homogenate has a bacteriostatic effect on UPEC and S. aureus strains and a bactericidal effect on both strains when the homogenate is diluted enough, possibly by acting on the dividing cells. Higher antimicrobial activity of the diluted AM homogenate is also favorable in the prospect of decreasing any possible side effects of the homogenate when used in medicine as treatment, as less homogenate would be applied.…”

Section: Discussionmentioning

confidence: 89%

Different Effects Of Amniotic Membrane Homogenate On The Growth Of Uropathogenic Escherichia coli, Staphylococcus aureus And Serratia marcescens

Sket

Ramuta

Erjavec

2019

IDR

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Due to the emergence and spread of bacterial strains resistant to antibiotics, the development of new antimicrobials is imperative. The antimicrobial effect of the amniotic membrane (AM) has been explored to a limited extent so far. Materials and methods: We collected 12 biological samples of AM homogenates and tested their antimicrobial effect on 4 pathogens, including the clinical strain of uropathogenic Escherichia coli (UPEC), the wild-type strain of Staphylococcus aureus, and the wild-type strain and a clinical strain of Serratia marcescens. To quantify the antibacterial effect of AM, we monitored the effect of AM homogenate on bacterial growth using plate count method and agar diffusion method. Additionally, minimal inhibitory concentrations (MICs) for AM homogenate dilutions were determined and S. marcescens growth in AM homogenate alone was evaluated. Results: Our results demonstrated that AM homogenate had a bacteriostatic effect on studied UPEC and S. aureus. Interestingly, when used in lower concentrations, the AM homogenate had a bactericidal effect on both strains. In contrast, S. marcescens was completely resistant to the growth-inhibitory substances of AM homogenate. Its growth was slightly accelerated in liquid culture medium in the presence of AM homogenate and the strain was able to grow in undiluted, 2-fold and 4-fold diluted AM homogenate. Conclusion: Obtained results illustrated that AM homogenate could be a candidate for treatments and prevention of UPEC and S. aureus infections, but not that of S. marcescens, whose growth is enhanced by AM homogenate. Moreover, the established liquid culture medium assay can be used as a time-and cost-effective method for a personalized evaluation of drug effect on the growth of chosen bacterial strains with parallel testing of resistance or susceptibility to multiple drugs. The susceptibility of bacteria to AM homogenate in solid and liquid culture media is encouraging for its use in biomedical applications.

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“…Since genome sequencing of the rebounded Wolbachia showed there were no gene changes that could account for the persistence, we postulate that the clusters are privileged sites in which Wolbachia persist in a low or inactive metabolic state, similar to what occurs with intracellular Toxoplasma gondii bradyzoites [56,57] and pathogenic intracellular bacteria including Mycobacterium tuberculosis, Treponema pallidum, Chlamydia spp. and Salmonella enterica which can cause persistent and latent infections [58][59][60][61][62][63][64][65][66]. Interestingly, bacterial toxin-antitoxin (TA) genes of the RelEB family thought to cause persister cell formation in insect-associated Wolbachia, were absent in Wolbachia from filarial nematodes, suggesting that TAs may not be involved in persister formation of Wolbachia within the clusters and that other mechanisms are likely at play [67][68][69][70].…”

Section: Plos Pathogensmentioning

confidence: 99%

The endosymbiont Wolbachia rebounds following antibiotic treatment

et al. 2020

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Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi jird model of infection. Initially, rifampicin treatment depleted Wolbachia in adult worms and simultaneously impaired female worm fecundity. However, during an 8month washout period, Wolbachia titers rebounded and embryogenesis returned to normal. Genome sequence analyses of Wolbachia revealed that despite the population bottleneck and recovery, no genetic changes occurred that could account for the rebound. Clusters of densely packed Wolbachia within the worm's ovarian tissues were observed by confocal microscopy and remained in worms treated with rifampicin, suggesting that they may serve as privileged sites that allow Wolbachia to persist in worms while treated with antibiotic. To our knowledge, these clusters have not been previously described and may be the source of the Wolbachia rebound.

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The Eagle Effect and Antibiotic-Induced Persistence: Two Sides of the Same Coin?

Cited by 53 publications

References 131 publications

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

<p>Different Effects Of Amniotic Membrane Homogenate On The Growth Of Uropathogenic <em>Escherichia coli</em>, <em>Staphylococcus aureus</em> And <em>Serratia marcescens</em></p>

The endosymbiont Wolbachia rebounds following antibiotic treatment

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