Investigation of the Effect of Antibiotic Resistance Developed in Klebsiella pneumoniae With Sub-Minimum Inhibitory Concentration and Cross-Antibiotic Resistance on Biofilm Formation
Antibiotic resistance is increasingly recognized as a critical global health challenge, rendering once-treatable infections more difficult to manage. This research explores how exposure to sub-minimum inhibitory concentrations (Sub-MIC) of antibiotics influences resistance development, cross-resistance, and biofilm formation in Klebsiella pneumoniae. Although K. pneumoniae is a Gram-negative, encapsulated, and non-motile bacterium that naturally inhabits the human gut, it can potentially cause severe infections under certain conditions.
The primary objective of this study is to examine how sub-MIC levels of antibiotics contribute to resistance development in K. pneumoniae, assess the emergence of cross-resistance patterns, and determine how these changes impact the ability of bacteria to form biofilms. Furthermore, the research evaluates how specific environmental factors, such as temperature (37°C and 45°C), varying glucose concentrations (ranging from 0% to 2.5%), and different resistance profiles, affect the biofilm-forming capacity of the bacteria.
The findings revealed that biofilm production was more pronounced at 37°C than 45°C, indicating that lower temperatures favour biofilm formation in K. pneumoniae. Additionally, an increase in glucose concentration correlated with reduced biofilm development. However, no clear association was identified between antibiotic resistance and biofilm formation.
Altuner EM, Akata I, Canlı K (2012) In vitro antimicrobial activity screening of Bovista nigrescens Pers. Kastamonu University Journal of Forestry Faculty 12(1):90-96.
Canli, K., Bozyel, M. E., & Altuner, E. M. (2017). In vitro antimicrobial activity screening of Maclura pomifera fruits against wide range of microorganisms. International Journal of Pharmaceutical Science Invention, 6(8), 19-22.
Canli K, Yetgin A, Akata I, Altuner EM (2016a) In vitro antimicrobial activity of Angelica sylvestris roots. International Journal of Biological Sciences 1(1):1-7.
Canli K, Yetgin A, Akata I, Altuner EM (2016b) In vitro antimicrobial activity screening of Rheum rhabarbarum roots. International Journal of Pharmaceutical Science Invention 5(2):01-04.
Calderon-Gonzalez R, Lee A, Lopez-Campos G, Hancock SJ, Sa-Pessoa J, Dumigan A, Bengoechea JA (2023) Modelling the gastrointestinal carriage of Klebsiella pneumoniae infections. Mbio 14(1):e03121-22. https://doi.org/10.1128/mbio.03121-22
Carabarin-Lima A, León-Izurieta L, Rocha-Gracia RDC, Castañeda-Lucio M, Torres C, Gutiérrez-Cazarez Z, Lozano-Zarain P (2016) First evidence of polar flagella in Klebsiella pneumoniae isolated from a patient with neonatal sepsis. Journal of medical microbiology 65(8):729-737. https://doi.org/10.1099/jmm.0.000291
Centers for Disease Control and Prevention research group (2019) Healthcare Facilities: Information about CRE. Centers for Disease Control and Prevention-Healthcare-Associated Infections (HAIs). https://www.cdc.gov/hai/organisms/klebsiella/klebsiella.html
dos Santos Goncalves M, Delattre C, Balestrino D, Charbonnel N, Elboutachfaiti R, Wadouachi A, Forestier C (2014) Anti-biofilm activity: a function of Klebsiella pneumoniae capsular polysaccharide. PLoS One 9(6):e99995. https://doi.org/10.1371/journal.pone.0099995
Esener AA, Roels JA, Kossen NWF (1983) The influence of temperature on the energetics of Klebsiella pneumoniae. Biotechnology and Bioengineering 25(8):2093-2098. https://doi.org/10.1002/bit.260250821
European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2018) Breakpoint tables for interpretation of MICs and zone diameters (Version 8.1). http://www.eucast.org
Guerra MES, Destro G, Vieira B, Lima AS, Ferraz LFC, Hakansson AP, Converso TR (2022) Klebsiella pneumoniae biofilms and their role in disease pathogenesis. Frontiers in cellular and infection microbiology 12:877995. https://doi.org/10.3389/fcimb.2022.877995
Li L, Gao X, Li M, Liu Y, Ma J, Wang X, Wang Z (2024) Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies. Frontiers in Cellular and Infection Microbiology 14:1324895. https://doi.org/10.3389/fcimb.2024.1324895
Li Y, Kumar S, Zhang L (2024) Mechanisms of antibiotic resistance and developments in therapeutic strategies to combat Klebsiella pneumoniae infection. Infection and Drug Resistance 17:1107-1119. https://doi.org/10.2147/IDR.S448623
Li Y, Kumar S, Zhang L, Wu H, Wu H (2023) Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae. Open Medicine 18(1):20230672. https://doi.org/10.1515/med-2023-0672
Li Y, Ni M (2023) Regulation of biofilm formation in Klebsiella pneumoniae. Frontiers in microbiology 14:1238482. https://doi.org/10.3389/fmicb.2023.1238482
Liu C, Wu Y, Zhang Y, Yan Z, Gu D, Zhou H, Zhang R (2025) Effectiveness of antimicrobial agent combinations against carbapenem-producing Klebsiella pneumoniae with KPC variants in China. Frontiers in Microbiology 15:1519319.
Paczosa MK, Mecsas J (2016) Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiol Mol Biol Rev 80(3):629-661. https://doi.org/10.1128/MMBR.00078-15
Qi L, Li H, Zhang C, Liang B, Li J, Wang L, Song H (2016) Relationship between antibiotic resistance, biofilm formation, and biofilm-specific resistance in Acinetobacter baumannii. Frontiers in microbiology 7:483. https://doi.org/10.3389/fmicb.2016.00483
Vuotto C, Longo F, Balice MP, Donelli G, Varaldo PE (2014) Antibiotic resistance related to biofilm formation in Klebsiella pneumoniae. Pathogens 3(3):743-758. https://doi.org/10.3390/pathogens3030743
Vuotto C, Longo F, Pascolini C, Donelli G, Balice MP, Libori MF, Varaldo PE (2017) Biofilm formation and antibiotic resistance in Klebsiella pneumoniae urinary strains. Journal of applied microbiology 123(4):1003-1018. https://doi.org/10.1111/jam.13533
Zhang F, Cheng W (2022) The mechanism of bacterial resistance and potential bacteriostatic strategies. Antibiotics 11(9):1215. https://doi.org/10.3390/antibiotics11091215
Zhang LY, Tian B, Huang YH, Gu B, Ju P, Luo Y, Wang L (2023) Classification and prediction of Klebsiella pneumoniae strains with different MLST allelic profiles via SERS spectral analysis. PeerJ 11:e16161. https://doi.org/10.7717/peerj.16161
Zurnaci M, Senturan M, Sener N, Gur M, Altinoz E, Sener I, Altuner EM (2021) Studies on antimicrobial, antibiofilm, efflux pump inhibiting, and ADMET properties of newly synthesised 1,3,4‐thiadiazole derivatives. ChemistrySelect 6(45):12571-12581. https://doi.org/10.1002/slct.202103573
):90-96.
Bozyel, M. E., Canli, K., Benek, A., Yetgin, A., & Altuner, E. M. (2021). Biochemical composition and in vitro antimicrobial activity of endemic Helichrysum arenarium ssp. aucheri ethanol extract. Fresenius Environmental Bulletin, 30(02), 869-875.
Canli, K., Bozyel, M. E., Turu, D., Benek, A., Simsek, O., & Altuner, E. M. (2023). Biochemical, Antioxidant Properties and Antimicrobial Activity of Steno-Endemic Origanum onites. Microorganisms, 11(8), 1987.
Canli, K., Yetgin, A., & Altuner, E. M. (2017). Antimicrobial activity screening of Allium tuncelianum. European Journal of Biomedical and Pharmaceutical Sciences, 4(4), 33-36.