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Thought on “Isolation and Phenotypic Characterization of Virulent Bacteriophages Against Multidrug-Resistant Escherichia Coli and Its Phage-Resistant Variant from Sewage Sources” [Letter]
Authors Mardiana M , Safari D, Sarassari R
Received 9 April 2024
Accepted for publication 25 April 2024
Published 2 May 2024 Volume 2024:17 Pages 1729—1730
DOI https://doi.org/10.2147/IDR.S472390
Checked for plagiarism Yes
Editor who approved publication: Professor Suresh Antony
Meity Mardiana, Dodi Safari, Rosantia Sarassari
Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, West Java, Indonesia
Correspondence: Meity Mardiana, Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, West Java, Indonesia, Email [email protected]
View the original paper by Mr Fikadu and colleagues
Dear editor
We have read the article written by Fikadu et al, in which they isolated and phenotypically characterized phages that infect multidrug-resistant (MDR) Escherichia coli.1 The emergence of MDR-E. coli has garnered significant attention in several countries, necessitating alternative therapies to address this issue.2,3 One such approach is the utilization of phage therapy. However, as highlighted by the authors in their article, the emergence of phage-resistant variants presents a new challenge, thus underscoring the perceived necessity of employing phage cocktails as a therapy strategy. This article provides a good initial step toward conducting further studies related to the utilization of phage cocktails for the treatment of bacterial infections. However, upon a more thorough review of this article, several suggestions for improving future studies are provided.
This study did not clearly disclose the method used to identify MDR in E. coli. The employment of minimum inhibitory concentration (MIC) method is favored as it is deemed more effective, as it can also identify the lowest concentration of antibiotics required to kill the pathogen. Moreover, the negative control used in this study should be consistent with the suspension in which the phage was suspended. The negative control should also have been loaded on the same plate in Figure 4 for a better comparison. Since the study focuses on phenotypic characterization, it would be beneficial for the authors to include electron microscopy (EM) data of the phages to determine if there are any morphological differences among the three phages. This could serve as a basis for understanding the antagonistic effect of the phage cocktail on phage-resistant variants, as discussed in the previous study, which indicated that antagonistic interactions are influenced by several factors, including phage types.4 Phenotypic analysis can also be conducted on phage-resistant strains to observe whether there are any phenotypic changes in the colonies formed on agar plates compared to the wild-type. For example, the mucoid shiny appearance, attributed to the overproduction of exopolysaccharide (EPS), acts as a physical barrier against phage infection, while edgy morphotype indicates increased expression of curli fimbriae and cellulose matrix components.5 This is a crucial step towards understanding phage resistance mechanisms for future research endeavors. Phage cocktail therapy is considered a promising approach to improving and overcoming the occurrences of phage-resistant variants. However, this recent study reveals that this may not always work, as evidenced by the antagonistic effects of the phage cocktail on the phage-resistant variants. It would also be more convincing to conduct sequential exposure during infection rather than combining all three phages simultaneously from the initial infection for comparison. In addition, it is important to note that the absence of plaque formation does not necessarily indicate resistance to the phage. Therefore, the authors could conduct an experiment involving the examination of the lysis curve of each host when challenged either with single or phage cocktails within the specified timeframe while also considering the multiplicity of infection (MOI) applied. This would allow us to understand how the phage–bacterium ratio influences the dynamics of bacterial lysis and develops more effective treatment strategies against bacterial infections.
Disclosure
The authors report no conflicts of interest in this communication.
References
1. Fikadu A, Amankwah S, Alemu B, et al. Isolation and phenotypic characterization of virulent bacteriophages against multidrug-resistant Escherichia coli and its phage-resistant variant from sewage sources. Infect Drug Resist. 2024;17:293–303. doi:10.2147/IDR.S441085
2. Ibrahim DR, Dodd CER, Stekel DJ, et al. Multidrug-resistant ESBL-producing E. coli in clinical samples from the UK. Antibiotics. 2023;12(1):169. doi:10.3390/antibiotics12010169
3. Patil S, Chen H, Chen Y, et al. Trends in antibiotic resistance patterns and burden of Escherichia coli infections in young children: a retrospective cross-sectional study in Shenzhen, China from 2014-2018. Infect Drug Resist. 2023;16:5501–5510. doi:10.2147/IDR.S425728
4. Niu YD, Liu H, Du H, et al. Efficacy of individual bacteriophages does not predict efficacy of bacteriophage cocktails for control of Escherichia coli O157. Front Microbiol. 2021;12:616712. doi:10.3389/fmicb.2021.616712
5. Mi Y, He Y, Mi J, et al. Genetic and phenotypic analysis of phage-resistant mutant fitness triggered by phage-host interactions. Int J Mol Sci. 2023;24(21):15594. doi:10.3390/ijms242115594
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