COLLATERAL SENSITIVITY PROFILING OF ANTIBIOTICS IN DRUG-RESISTANT ESCHERICHIA COLI: A COMPARATIVE PHARMACOLOGICAL ANALYSIS
DOI:
https://doi.org/10.65327/bp.v12i3.2543Keywords:
Escherichia coli, collateral sensitivity, cross-resistance, minimum inhibitory concentration, antimicrobial resistanceAbstract
Antimicrobial resistance in Escherichia coli continues to limit the effectiveness of commonly used antibiotics and has increased interest in collateral sensitivity as a potential strategy for exploiting resistance-associated trade-offs. Comparative minimum inhibitory concentration (MIC) profiling can help distinguish collateral sensitivity from cross-resistance patterns. To compare MIC-based antibiotic susceptibility between susceptible and drug-resistant E. coli and identify fold-change patterns consistent with cross-resistance or potential collateral sensitivity. A secondary comparative pharmacological analysis was performed using publicly available phenotypic antimicrobial susceptibility data. E. coli ATCC 25922 served as the susceptible reference strain and E. coli LSI-770 as the resistant comparator. MIC values, susceptibility classifications, MIC fold changes, log₂ fold changes, and agreement between BLAST-derived and reference broth microdilution measurements were evaluated. The reference strain remained susceptible to all 11 evaluated antibiotics. Direct comparison was available for doxycycline, levofloxacin, and cefazolin. The resistant strain showed marked MIC elevation for all three agents. Levofloxacin demonstrated the greatest MIC increase, followed by doxycycline, while cefazolin showed off-scale resistance. No negative MIC fold change was observed, indicating cross-resistance rather than detectable collateral sensitivity. BLAST measurements showed generally strong agreement with reference broth microdilution. The resistant E. coli strain exhibited broad reduced susceptibility across matched antibiotics, supporting a cross-resistance profile. Larger strain panels and broader antibiotic matrices are needed to identify reproducible collateral-sensitivity relationships.
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Almutairy, B. (2024). Extensively and multidrug-resistant bacterial strains: case studies of antibiotics resistance. Frontiers in Microbiology, 15, 1381511.
Askari, P., Namaei, M. H., Ghazvini, K., & Hosseini, M. (2021). In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria. BMC Pharmacology and Toxicology, 22(1), 42.
Card, K. J., Crozier, D., Durmaz, A., Gray, J., Creary, J., Stocks, A., ... & Scott, J. G. (2025). Evolution under vancomycin selection drives divergent collateral sensitivity patterns in Staphylococcus aureus. Proceedings of the National Academy of Sciences, 122(39), e2507962122.
Carolus, H., Sofras, D., Boccarella, G., Jacobs, S., Biriukov, V., Goossens, L., ... & Van Dijck, P. (2024). Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris. Nature microbiology, 9(11), 2954-2969.
Chaudhary, S., Ali, Z., Tehseen, M., Haney, E. F., Pantoja-Angles, A., Alshehri, S., ... & Mahfouz, M. (2023). Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens. Nature Communications, 14(1), 1464.
Cristina, H., Jerónimo, R. B., León-Sampedro, R., Jana, P., Rafael, C., & Álvaro, S. M. (2021). Collateral sensitivity associated with antibiotic resistance plasmids. eLife, 10.
Fodor, A., Abate, B. A., Deák, P., Fodor, L., Gyenge, E., Klein, M. G., ... & Makrai, L. (2020). Multidrug resistance (MDR) and collateral sensitivity in bacteria, with special attention to genetic and evolutionary aspects and to the perspectives of antimicrobial peptides—a review. Pathogens, 9(7), 522.
Gu, Y., Wang, S., Huang, L., Sa, W., Li, J., Huang, J., ... & Cheng, G. (2020). Development of resistance in Escherichia coli ATCC25922 under exposure of sub-inhibitory concentration of olaquindox. Antibiotics, 9(11), 791.
Herencias, C., Rodríguez-Beltrán, J., Leon-Sampedro, R., Alonso-del Valle, A., Palkovičová, J., Canton, R., & San Millan, A. (2021). Collateral sensitivity associated with antibiotic resistance plasmids. Elife, 10, e65130.
Kittle, J., Jr., & Lwande, J. (2025). A rapid bacterial labeling method for phenotypic antimicrobial susceptibility testing [Data set]. Mendeley Data. DOI:10.17632/22bcmpzrh5.1
Kroemer, N., Amann, L. F., Farooq, A., Pfaffendorf, C., Martens, M., Decousser, J. W., ... & Wicha, S. G. (2024). Pharmacokinetic/pharmacodynamic analysis of ceftazidime/avibactam and fosfomycin combinations in an in vitro hollow fiber infection model against multidrug-resistant Escherichia coli. Microbiology Spectrum, 12(1), e03318-23.
Liu, D. Y., Phillips, L., Wilson, D. M., Fulton, K. M., Twine, S. M., Wong, A., & Linington, R. G. (2023). Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance. Nature Communications, 14(1), 1976.
Mahmud, H. A., & Wakeman, C. A. (2024). Navigating collateral sensitivity: insights into the mechanisms and applications of antibiotic resistance trade-offs. Frontiers in Microbiology, 15, 1478789.
Maltas, J., Huynh, A., & Wood, K. B. (2021). Dynamic collateral sensitivity profiles highlight challenges and opportunities for optimizing antibiotic sequences. bioRxiv, 2021-12.
Maltas, J., Huynh, A., & Wood, K. B. (2025). Dynamic collateral sensitivity profiles highlight opportunities and challenges for optimizing antibiotic treatments. PLoS Biology, 23(1), e3002970.
Marzouk, E., & Almuzaini, A. M. (2025). Phenotype-First Diagnostic Framework for Tracking Fluoroquinolone Resistance in Escherichia coli. Diagnostics, 15(22), 2831.
Morales-Durán, N., León-Buitimea, A., & Morones-Ramírez, J. R. (2024). Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions. Heliyon, 10(6).
Paranos, P., Vourli, S., Pournaras, S., & Meletiadis, J. (2022). Assessing clinical potential of old antibiotics against severe infections by multi-drug-resistant gram-negative bacteria using in silico modelling. Pharmaceuticals, 15(12), 1501.
Sancak, B., Kırbaş, E., Ari, O., & Durmaz, R. (2026). Genomic characterization of colistin heteroresistance in Acinetobacter baumannii: Evidence for lpxD deletion and collateral sensitivity. Journal of Antimicrobial Chemotherapy, 81(4), dkag076.
Singh, S., Adhikari, S., Varshney, N., Rani, C., Kumar, A., Kumar, R., & Jha, H. C. (2025). Overcoming antimicrobial resistance in Helicobacter pylori: the roles of collateral sensitivity and biofilm dynamics. Journal of Antimicrobial Chemotherapy, 80(9), 2433-2441.
Starr, C. G., Ghimire, J., Guha, S., Hoffmann, J. P., Wang, Y., Sun, L., ... & Wimley, W. C. (2020). Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria. Proceedings of the National Academy of Sciences, 117(15), 8437-8448.
Yang, K., Rasouly, A., & Nudler, E. (2025). Collateral sensitivity and genetic vulnerability of antibiotic resistance. Trends in Microbiology.
Yekani, M., Azargun, R., Sharifi, S., Nabizadeh, E., Nahand, J. S., Ansari, N. K., ... & Soki, J. (2023). Collateral sensitivity: An evolutionary trade‐off between antibiotic resistance mechanisms, attractive for dealing with drug‐resistance crisis. Health Science Reports, 6(7), e1418.
Yousha, N. A., Badhan, S. I., Dina, S. D., & Ahsan, M. D. (2023). In vitro collateral sensitivity: a potential approach against multiple antibiotic resistant bacteria (Doctoral dissertation, Brac University).
Zhang, Y., Tao, M., Wang, R., Shi, Z., Li, P., Tang, S., ... & Zhou, Y. (2024). Collateral sensitivity to gamithromycin in ciprofloxacin-resistant Streptococcus suis is driven by increasing intracellular antibiotic accumulation. Journal of Integrative Agriculture.
Zhao, X. L., Chen, Z. G., Yang, T. C., Jiang, M., Wang, J., Cheng, Z. X., ... & Peng, X. X. (2021). Glutamine promotes antibiotic uptake to kill multidrug-resistant uropathogenic bacteria. Science Translational Medicine, 13(625), eabj0716.
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