Main Article Content

Abstract

Klebsiella  pneumoniae is the Enterobacteriaceae family can be found in the environment, humans and animals. These bacteria are common causes of hospital, community and healthcare associated infections. Third generation cephalosporin (3GC) is one of the broad spectrum cephalosporin antibiotic that is commonly used to treat this infection. Use of antibiotics without appropriate sensitivity guidance, natural antibiotic resistant bacteria and MGE mediated horizontal gene transfer have led to increased resistance in 3GC. Mobile genetic elements such as insertion sequences (IS), transposons, integrons and resistance plasmids facilitate horizontal gene transfer between bacteria. This element can move between chromosomes or plasmids, transferring genetic material to the recipient bacteria. Horizontal gene transfer can occur by conjugation, transformation, transduction and vesiduction. IS, transposons, integrons and resistance plasmids associated with 3GC resistance are discussed in this article. We analysed the role of these MGEs in 3GC resistance in K. pneumoniae using PRISMA methods from different academic sources. We found an association of MGE with ESBL and AmpC betalactamase gene. This element promotes the transfer of resistance genes to other bacteria. Understanding the MGEs that play a role in the spread of antibiotic resistance genes in K. pneumoniae is important to control the spread of the gene.

Keywords

3GC, K. pneumoniae, virulence factor, resistance, MGE

Article Details

How to Cite
1.
Enggel Y, Tjampakasari CR, Kiranasari A. Mobile Genetic Elements Associated with Third-Generation Cephalosporin Resistance in Klebsiella pneumoniae. EKSAKTA [Internet]. 2024May20 [cited 2024Jun.21];25(02):177-8. Available from: https://eksakta.ppj.unp.ac.id/index.php/eksakta/article/view/502

References

  1. Karami, P., Zarei, O., Kosari, F., Alikhani, M. Y., Zandkarimi, E., Zarandi, E. R., Taheri, M. (2020). Prevalence of common nosocomial infections and evaluation of antibiotic resistance patterns in patients with secondary infections in Hamadan, Iran. Infect Drug Resist, 3(2365).
  2. Denissen, J., Reyneke, B., Reyneke, M. S., Havenga, B., Barnard, T., Khan, S., Kan, W. (2022). Prevalence of ESKAPE pathogens in the environment: antibiotic resistance status, community-acquired infection and risk to human health. International Journal of Hygiene and Environmental Health, 244(114006).
  3. Mohd Asri, N. A., Ahmad, S., Mohamud, R., et al. (2021). Global prevalence of nosocomial multidrug-resistant Klebsiella pneumoniae: a systematic review and meta-analysis. Antibiotics (Basel), 10(12): 1508.
  4. Akram, F., Imtiaz, M., Ul Haq, I. (2023). Emergent crisis of antibiotic resistance: a silent pandemic threat to 21st Century. Microbial Pathogenesis, 174(105923).
  5. Arumugham, B. V., Gujarathi, R., Cascella, M. (2023). Third-generation cephalosporins. Treasure Island (FL). StatPearls Publishing.
  6. Mark, D. G., Hung, Y. Y, Salim, Z., Tarlton, N. J, Torres, E., Frazee, B. W. (2021). Third-generation cephalosporin resistance and associated discordant antibiotic treatment in emergency department febrile urinary tract infections. Annals of Emergency Medicine, 78(3), 357-369.
  7. Tekele, S. G., Teklu, D. S., Tullu, K. S., Birru, S. K., Legese, M. H. (2020). Extended-spectrum beta-lactamase and AmpC beta-lactamases producing gram negative bacilli isolated from clinical specimens at International Clinical Laboratories, Addis Ababa, Ethiopia. PLoS One, 15(11): e0241984.
  8. Rocha, J., Ferreira, C., Mil Homens, D., Busquets, A., Fialho, A. M., Henriques, I., Gomila, M., Manaia, C.M. (2022). Third generation cephalosporin-resistant Klebsiella pneumoniae thriving in patients and in wastewater: what do they have in common?. BMC Genomics, 23(72).
  9. Haudiquet, M., Buffet, A., Rendueles, O., Rocha, P. C. E. (2021). Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae. PLOS Biology, 19(7), e3001276.
  10. Wang, L., Zhu, M., Yan, C., Zhang, Y., He, X., Wu, L., et al. (2023). Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China. Front. Microbiol, 14(985102).
  11. Hawkey, J., Wyres, K. L., Judd, L. M., Harshegyi, T., Blakeway, L., Wick, R. R., et al. (2022). ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting. Genome Med, 14(97).
  12. Quan, J., Hu, H., Zhang, H. Meng, Y., Liao, W., Zhou, J., et al. (2023). Investigating possible interspecies communication of plasmids associated with transfer of third-generation cephalosporin, quinolone, and colistin resistance between simultaneously isolated Escherichia coli and Klebsiella pneumoniae. Microbiology Spectrum, 11(3), e03554-22.
  13. Rawy, D.K., El-Mokhtar, M.A., Hemida, S.K., Askora, A., Yousef, N. (2020). Isolation, characterization and identification of Klebsiella pneumoniae from Assiu University Hospital and sewage water in Assiut Governorate, Egypt. Assiut Univ. J. of Botany and Microbiology, 49(2), 60-76.
  14. Sydow, K., Eger, E., Schwabe, M., Heiden, S. E., Bohnert, J. A., Franzenburg, et al. (2022). Geno- and phenotypic characteristics of a Klebsiella pneumoniae ST20 isolate with unusual colony morphology. Microorganisms, 10(10), 2063.
  15. Dong, N., Yang, X., Chan, E. W. C., Zhang, R., Chen, S. (2022). Klebsiella Species: taxonomy, hypervirulence and multidrug resistance. EbioMedicine, 79(103998).
  16. Chen, J., Zhang, H., Liao, X. (2023). Hypervirulent Klebsiella pneumoniae. Infect Drug Resist, 16, 5243–5249.
  17. Ferrer, S. G., Peñaloza, H. F., Budnick, J. A., Bain, W. G., Nordstrom, H. R., Lee, J. S., Tyne, D. V. (2021). Finding order in the chaos: outstanding questions in Klebsiella pneumoniae. Pathogenesis. Infect Immun, 89(4): e00693-20.
  18. Deleo, F. R., Porter, A. R., Kobayashi, S. D., Freedman, B., Hao, M., Jiang, J., et al. (2023). Interaction of multidrug-resistant hypervirulent Klebsiella pneumoniae with components of human innate host defense. mBio, 14(5), e01949-23.
  19. Zhu, J., Wang, T., Chen, L., Du, H. (2021). Virulence factors in hypervirulent Klebsiella pneumoniae. Front. Microbiol, 12, 642484.
  20. Guerra, M. E. S., Destro, G., Vieira, B., Lima, A. S., Ferraz, L. F. C., Hakansson, A. P, et al. (2022). Klebsiella pneumoniae biofilms and their role in disease pathogenesis. Front Cell Infect Microbiol, 12(877995).
  21. Haudiquet, M., Buffet, A., Rendueles, O., Rocha, E. P. C. (2021). Interplay between the cell envelope and mobile genetic elements shapes gene flow in populations of the nosocomial pathogen Klebsiella pneumoniae. PLOS Biology, 19(7), e3001276.
  22. Arumugham, V.B., Gujarathi, R., Cascella, M. (2023). Third-generation cephalosporins. Treasure Island (FL). StatPearls Publishing.
  23. Gad, S. C. (2023). Cephalosporins. Reference Module in Biomedical Sciences.
  24. Lin, X., Kück, U. (2022). Cephalosporins as key lead generation beta-lactam antibiotics. Applied Microbiology and Biotechnology, 106, 8007–8020.
  25. Kato, T., Tanaka, I., Seyama, Y., Sekikawa, R., Suzuki, S., Nagasawa, M., Hino, S. The effectiveness of prescription support and treatment reporting system on the appropriate usage of oral third-generation cephalosporins. Journal of Infection and Chemotherapy, 27(3), 419-423.
  26. Asmarawati, T. P., Djojodimedjo, T., Andhika, D. P., Rusli, M., Qibtiyah, M., Mahdi, B. A., et al. (2023). The use of antibiotic prophylaxis in patients undergoing urologic procedures in an academic hospital Surabaya: A retrospective study. J Infect Dev Ctries, 17, 874–880.
  27. Fulgenzio, C., Massari, M., Traversa, G., Da Cas, R., Ferrante, G., Aschbacher, R., et al. (2021). Impact of prior antibiotic use in primary care on Escherichia coli resistance to third generation cephalosporins: a case-control study. Antibiotics, 10(4), 451.
  28. Denissen, J., Reyneke, B., Waso-Reyneke, W., Havenga, B., Barnard, T., Khan, S., Khan, W. (2022). Prevalence of ESKAPE pathogens in the environment: Antibiotic resistance status, community-acquired infection and risk to human health. International Journal of Hygiene and Environmental Health, 244(2022), 114006.
  29. Ngoi, S. T., Chong, C. W., Ponnampalavanar, S. S. L. S, Tang, S. N., Idris, N., Jabar, K. A., et al. (2021). Genetic mechanisms and correlated risk factors of antimicrobial-resistant ESKAPEE pathogens isolated in a tertiary hospital in Malaysia. Antimicrob Resist Infect Control, 10, 70.
  30. Renggli, L., Gasser, M., Plüss-Suard, C., et al. (2022). Temporal and structural patterns of extended-spectrum cephalosporin-resistant Klebsiella pneumoniae incidence in Swiss Hospitals. Journal of Hospital Infection, 120, 36-42.
  31. Sethuvel, D. P. M., Bakthavatchalam, Y. D., Karthik, M. et al. (2023). β-Lactam resistance in ESKAPE pathogens mediated through modifications in penicillin-binding proteins: An overview. Infect Dis Ther 12, 829–841.
  32. Li, Y., Kumar, S., Zhang, L., Wu, H., Wu, H. (2023). Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae. Open Med (Wars), 18(1), 20230707.
  33. De Oliveira, D. M. P, Forde, B. M., Kidd, T. I., Harris, P. N. A. (2020). Antimicrobial resistance in ESKAPE pathogens. Clin Microbiol Rev, 13(33), 3.
  34. Ejaz, H. (2022). Analysis of diverse β-lactamases presenting high-level resistance in association with OmpK35 and OmpK36 porins in ESBL-producing Klebsiella pneumoniae. Saudi Journal of Biological Sciences, 29(5), 3440-3447.
  35. Ashwath, P., Sannejal, A.D. (2022). The action of efflux pump genes in conferring drug resistance to Klebsiella species and their inhibition. Journal of Health and Allied Sciences NU, 12(1): 24-31.
  36. Guera, M., E., S., Destro, G., Vieira, B., Lima, A. S., Ferraz, L., F., C., Hakansson, A. P., et al. (2022). Klebsiella pneumoniae biofilms and their role in disease pathogenesis. Front. Cell. Infect. Microbiol., 12, 877995.
  37. Khedkar, S., Smyshlyaev, G., Letunic, I., Maistrenko, O., M., Coelho, L., P., et al. (2022) Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic Genomes. Nucleic Acids Res., 50(6), 3155–3168.
  38. Kim, D., W., Cha, J., C. (2021). Antibiotic resistome from the one-health perspective: understanding and controlling antimicrobial resistance transmission.. Experimental & Molecular Medicine, 53, 301–309.
  39. Decano, A. G., Pettigrew, K., Sabiiti, W., Sloan, D. J., Neema, S., Bazir, J., et al. (2021). Pan-resistome characterization of uropathogenic Escherichia coli and Klebsiella pneumoniae strains circulating in Uganda and Kenya, isolated from 2017–2018. Antibiotics, 10(12), 1547.
  40. Fredriksen, S., de Warle, S., Van Baarlen, P., Boekhorst, J., Wells, J. M. (2023). Resistome expansion in disease-associated human gut microbiomes. Microbiome 11, 166.
  41. Zhou, H., Beltran, J. P., Brito, I. L. (2021). Functions predict horizontal gene transfer and the emergence of antibiotic resistance. Science Advances, 7(43), eabj5056.
  42. Honceriu, I. (2022). Acquired antibiotic resistance. J Exp Molec Biol, 23(1), 54-65.
  43. Asghari, B., Goodarzi, R., Mohammadi, M., Nouri, F., Taheri, M. (2021). Detection of mobile genetic elements in multidrug-resistant Klebsiella pneumoniae isolated from different infection sites in Hamadan, west of Iran. BMC Res Notes, 14(1), 330.
  44. Dai, P., Hu, D. (2022). The making of hypervirulent Klebsiella pneumoniae. J Clin Lab Anal, 36, e24743.
  45. Consuegra, J., Gaffé, J., Lenski, R. E., Hindré, T., Barrick, J. E., Tenaillon, O., Schneider, D. (2021). Insertion-sequence-mediated mutations both promote and constrain evolvability during a long-term experiment with bacteria. Nature Communications, 12(980).
  46. Golubov, A. (2021) . Genome instability in bacteria: causes and consequences. From Virus to Human Application, 2(26), 73-90.
  47. Perdigão, J., Modesto, A., Pereira, A. L., Neto, O., Matos, V., Godinho, A., et al. (2020). Whole-genome sequencing resolves a polyclonal outbreak by extended-spectrum beta-lactam and carbapenem-resistant Klebsiella pneumoniae in a Portuguese tertiary-care hospital. Microbial Genomics, 7, 000349.
  48. Kieffer, N., Poirel, L., Mueller, L., Mancini, S., Nordmann, P. (2020). ISEcp1-Mediated transposition leads to fosfomycin and broad-spectrum cephalosporin resistance in Klebsiella pneumoniae. Antimicrobial Agents and Chemotherapy, 64(5).
  49. Awosile, B. B., Agbaje, M. (2021). Genetic environments of plasmid-mediated blaCTXM-15 beta-lactamase gene in Enterobacteriaceae from Africa. Microbiol. Res., 12(2), 383-394.
  50. Jiang, Y., Wang, Y., Hua, X., Qu, Y., Peleg, A. Y., Yu, Y. (2020). Pooled plasmid sequencing reveals the relationship between mobile menetic elements and entimicrobial resistance genes in clinically isolated Klebsiella pneumoniae. Genomics, Proteomics & Bioinformatics, 18(5), 539–548.
  51. Sundaresan, A. B., Vincent, K., Mohan, G. B., Ramakrishnan, J. (2022). Association of sequence types, antimicrobial resistance and virulence genes in Indian isolates of Klebsiella pneumoniae: a comparative genomics study. Journal of Global Antimicrobial Resistance, 30(2022), 431-441.
  52. Lipszyc, A., Szuplewska, M., Bartosik, D. (2022). How do transposable elements activate expression of transcriptionally silent antibiotic resistance genes?. Int. J. Mol. Sci., 23(15), 8063.
  53. Castanheira, M., Simner, P. J., Bradford, P. A. (2021). Extended-spectrum β-Lactamases: an update on their characteristics, epidemiology and detection. JAC-Antimicrobial Resistance, 3(3).
  54. Altayb, H. N., Elbadawi, H. S., Alzahrani, F. A., Baothman, O., Kazmi, I., Nadeem, M. S., Hosawi, S., Chaieb, K. (2022). Co-occurrence of β-lactam and aminoglycoside resistance determinants among clinical and environmental isolates of Klebsiella pneumoniae and Escherichia coli: A genomic approach. Pharmaceuticals, 15(8), 1011.
  55. Sabbagh, P., Rajabnia, M., Maali, A., Ferdosi-Shahandashti, E. (2021). Integron and its role in antimicrobial resistance: A literature review on some bacterial pathogens. Iran J Basic Med Sci, 24(2), 136–142.
  56. Delarampour, A., Ghalehnoo, R. Z., Khademi, F., Vaez, H. (2020). Antibiotic resistance patterns and prevalence of class I, II and III integrons among clinicaI isolates of Klebsiella pneumoniae. Le Infezioni in Medicina, 1, 64-69.
  57. Wang, L., Zhu, M., Yan, C., Zhang, Y., He, X., Wu, L., et al. (2023). Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China. Front. Microbiol, 14, 985102.
  58. Delarampour, A., Ghalehnoo, Z. R., Khademi, F., Vaez, H. (2020). Antibiotic resistance patterns and prevalence of class I, II and III integrons among clinical isolates of Klebsiella pneumoniae. Le infezioni in medicina, 28(1), 64-69.
  59. Rodriguez, C. T., Dawson, F., Cameron, J., Seah, C., Reid, M. (2022). Prevalence and distribution of AmpC beta-lactamase producing Escherichia coli and Klebsiella pneumoniae isolates obtained from urine samples at a tertiary care hospital in the Caribbean. Front. Cell. Infect. Microbiol, 12, 1015633.
  60. Hawkey, J., Wyres, K. L., Judd, L. M., Harshegyi, T., Blakeway, L., et al. (2022). ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting. Genome Medicine, 14(97).
  61. Pedersen, T., Tellevik, M. G., Kommedalc, Ø., Lindemann, P. C., Moyo, S. J. (2020). Horizontal plasmid transfer among Klebsiella pneumoniae isolates is the key factor for dissemination ofeExtended-spectrum β-lactamases among children in Tanzania. Clinical Science and Epidemiology, 5(4).
  62. Ramirez, M. S., Iriarte, A., Lamothe, R. R., Sherratt, D. J., Tolmasky, M. E. (2019). Small Klebsiella pneumoniae plasmids: neglected contributors to antibiotic resistance. Front. Microbiol, 20(10), 2182.