Gram-negative bacilli from the Enterobacteriaceae family. β-Lactamases with extended substrate spectrum (ESBL) – characteristics, selected molecular aspects of antibiotic resistance, diagnostics – short literature review
DOI:
https://doi.org/10.24917/25438832.9.Keywords:
mechanisms of resistance, mutations, gram-negative bacteriaAbstract
The Enterobacteriaceae family includes various types of Gram-negative bacteria. Microorganisms treated with antibiotics modify “resistance mechanisms”. An example is selected bacteria from the Enterobacteriaceae family, strains of which can produce extended-spectrum β-lactamases (ESBLs). β-lactamases are enzymes that can hydrolyse penicillins, cephalosporins (including third- and fourth-generation, C3G and C4G) and aztreonam, resulting in the development of infection, and fewer therapeutic options. Diagnosis is impeded by the presence of different phenotypes of ESBL resistance to β-lactamases. It leads to detailed substrate preferences of specific ESBL types, designated inhibitor sensitivity, and degree of enzymatic activity and expression, providing the basis for several identification steps. A single mutation in the active site of the enzyme led to the formation of known ESBLs (TEM-1, TEM-2 and SHV-1). Newer enzymes (CTX-M) are derived from cephalosporinases produced by certain plant bacterial strains (e.g. Kluyvera ascorbata), which are then inserted into mobile genetic elements. To date, more than 350 different ESBL enzymes have been identified.
Downloads
Metrics
References
Achouak, W., Heulin, T., Pagès, J-M. (2001). Multiple facets of bacterial porins. FEMS Microbiology Letters, 199(1), 1–7. https://pubmed.ncbi.nlm.nih.gov/11356559/
Amyes, S.G.B., Gemmell C.G. (1992). Antibiotic resistance in bacteria. Medical Microbiology, 36, 4–29. https://doi.org/10.1099/00222615-36-1-4
Babini, G.S., Livermore D.M. (2000). Antimicrobial resistance amongst Klebsiella spp. collected from intensive care units in Southern and Western Europe in 1997–1998, Journal of Antimicrobial Chemotherapy, 45, 183–189. https://doi.org/10.1093/jac/45.2.183
Baraniak, A., Fiett, J., Mrówka, A., Walory, J., Hrynkiewicz, W., Gniadkowski, M. (2005). Evolution of TEM- Type Extended-Spectrum β-Lactamases in Clinical Enterobacteriaceae Strains in Poland. Antimicrobial Agents and Chemotherapy, 49(5), 1872–1880. https://doi.org/10.1128/AAC.49.5.1872-1880.2005
Berbers, B., Vanneste, K., Roosens, N.H.C.J., Marchal, K., Ceyssens, P.-J., De Keersmaecker, S.C.J. (2023). Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinical Shigella and Salmonella isolates in Belgium. Microbial Genomics, 9(1), mgen000925. https://doi.org/10.1099/mgen.0.000925
Bonnet, R. (2004). Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrobial Agents Chemotherapy, 48(1), 1–14. https://doi.org/10.1128/AAC.48.1.1-14.2004
Breurec, S., Guessennd, N., Timinouni, M., Le, T.T.H., Cao, V., Ngandjio, A., Randrianirina, F., Thiberge, J.M., Kinana, A., Dufougeray, A., Perrier-Gros-Claude, J.D., Boisier, P., Garin, B., Brisse, S. (2013). Klebsiella pneumoniae resistant to third- generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258. Clinical Microbiology Infection, 19, 349–355. https://doi.org/10.1111/j.1469-0691.2012.03805.x
Buchanan, S.K (1999). β-Barrel proteins from bacterial outer membranes: structure, function and refolding. Current Opinion Structural Biology, 9, 455–461. https://doi.org/10.1016/S0959-440X(99)80064-5
Bush, K., Bradford, P.A. (2016). β-Lactams and β-lactamase inhibitors: an overview. Cold Spring Harbor Perspectives Medicine, 6(8), a 025347. https://doi.org/10.1101/cshperspect.a025247
Bush, K., Jacoby, G.A. (2010). Updated functional classification of beta-lactamases. Antimicrobial Agents Chemotherapy, 54, 969–976. https://doi.org/10.1128/AAC.01009-09
Bush, K., Jacoby, G.A., Medeiros, A.A. (1995). A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrobial Agents Chemotherapy, 39, 1211–1233. https://doi.org/10.1128/AAC.39.6.1211
Cagnacci, S., Gualco, L., Roveta, S., Mannelli, S., Borgianni, L., Docquier, J.D. (2008). Bloodstream infections caused by multidrug-resistant Klebsiella pneumonia producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian outbreak. Journal Antimicrobial Chemotherapy, 61(2), 296–300. https://doi.org/10.1093/jac/dkm471
Carvalho, A.C., Barbosa, A.V., Arais, L.R., Ribeiro, P.F., Carneiro, V.C., Cerqueira, A.M.F. (2016). Resistance Patterns, ESBL Genes, and Genetic Relatedness of Escherichia Coli from Dogs and Owners. Brazilian Journal of Microbiology, 47(1), 150–158. https://doi.org/10.1016/j.bjm.2015.11.005
Castanheira, M., Simner, P.J., Bradford, P.A. (2021). Extended-spectrum β-lactamases: An update on their characteristics, epidemiology and detection. JAC-Antimicrobal Resistance, 3, dlab092. https://doi.org/10.1093/jacamr/dlab092
CBMAR: Comprehensive Beta-lactamase Molecular Annotation Resource. β-lactamases. http://proteininformatics.org/mkumar/lactamasedb/lactamase.html (Access: 30 May 2024).
Cepas, V., López, Y., Muñoz, E., Rolo, D., Ardanuy, C., Martí, S., Xercavins, M., Horcajada, J.P., Bosch, J., Soto, S.M. (2019). Relationship between biofilm formation and antimicrobial resistance in gram-negative bacteria. Microbial Drug Resistance, 25, 72–79. https://doi.org/10.1089/mdr.2018.0027
Chung, P.Y. (2016). The emerging problems of Klebsiella pneumoniae infections: carbapenem resistance and biofilm formation. FEMS Microbiology Letters, 363(20), fnw219. http://doi.org/10.1093/FEMSLE/FNW219
Coque, T.M., Novais, A., Carattoli, A., Poirel, L., Pitout, J., Peixe, L., Baquero, F., Canton, R., Nordmann, P. (2008). Dissemination of clonally related Escherichia coli strains expressing extended-spectrum β-lactamase CTX-M-15. Emerging Infectious Diseases, 14, 195–200. https://doi.org/10.3201/eid1402.070350
Desai, S., Sanghrajka, K., Gajjar, D. (2019). High adhesion and increased cell death contribute to strong biofilm formation in Klebsiella pneumoniae. Pathogens, 8(4), 277. https://doi.org/10.3390/pathogens8040277
Doménech-Sánchez, A., Martínez- Martínez, L., Hernández- Allés, S., del Carmen Conejo, M., Pascual, A, Tomás, J.M, Benedí, V.J. (2003). Rolle of Klebsiella pneumoniae OmpK35 Porin in antimicrobial resistance. Antimicrobial Agents Chemotherapy, 47(10), 3332–3335. https://doi.org/10.1128/AAC.47.10.3332-3335.2003
Dzierżanowska, D. (2018). Mechanizmy bakteryjnej oporności na antybiotyki i chemioterapeutyki. W: Antybiotykoterapia praktyczna. Wydawca: Alfa Medica Press. [In Polish]
Florensa, A., Kaas, R., Clausen, P., Aytan-Aktug, D., Aarestrup, F. (2022). ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes. Microbial Genomics, 8(1), 000748. https://doi.org/10.1099/mgen.0.000748
Founou, R., Founou, L., Allam, M., Ismail, A., Essack, S. (2019). Whole genome sequencing of extended spectrum β-Lactamase (ESBL)-producing Klebsiella pneumoniae isolated from hospitalized patients in KwaZulu-Natal, South Africa. Scientific Reports, 9(1), 6266. https://doi.org/10.1038/s41598-019-42672-2
Gniadkowski, M. (2001). Evolution and epidemiology of extended spectrum β-lactamases (ESBLS) and producing microorganisms. Clinical Microbiology and Infection, 7(11), 597–608. https://doi.org/10.1046/j.1198-743x.2001.00330.x
Hasman, H., Mevius, D., Veldman, K., Olesen, I., Aarestrup, F.M. (2005). β-Lactamases among extended-spectrum β-lactamase (ESBL)-resistant Salmonella from poultry, poultry products and human patients in the Netherlands. Journal of Antimicrobial Chemotherapy, 56(1), 115–121. https://doi.org/10.1093/jac/dki190
Hopkins, K.L., Liebana, E., Villa, L., Batchelor, M., Threlfall, E.J., Carattoli, A. (2006). Replicon typing of plasmids carrying CTX-M or CMY β-lactamases circulating among Salmonella and Escherichia coli isolates. Antimicrobial Agents Chemotherapy, 50, 3203–3206. https://doi.org/10.1128/AAC.00149-06
Hryniewicz, W., Kuch, A., Wanke-Rytt, M., Żukowska, A. (red.) (2022). Pałeczki Enterobacterales wytwarzające karbapenemazy (CPE). Epidemiologia, diagnostyka, leczenie i profilaktyka zakażeń. Wyd. Narodowy Instytut Leków, Warszawa. [In Polish].
Humeniuk, C., Arlet, G., Gautier V., Grimont, P., Labia, Roger., Philippon A. (2002). β-lactamases of Kluyvera ascorbata, probable progenitors of some plasmid- encoded CTX-M types. Antimicrobial Agents and Chemotherapy – ASM Journals, 46(9), 3045–3049. http://doi.org/10.1128/aac.46.9.3045-3049.2002
Huy, T.X.N. (2024). Overcoming Klebsiella pneumoniae antibiotic resistance: new insights into mechanisms and drug discovery. Beni-Suef University Journal of Basic and Applied Sciences, 13(13). https://doi.org/10.1186/s43088-024-00470-4
Jabłoński, A., Zębek, S., Mokrzycka, A. (2010). Selected resistance mechanisms of bacteria to chemotherapeutics. Medycyna Weterynaryjna, 66(7), 449–452. [In Polish]
Kliebe, C., Nies, B.A., Meyer, J.F., Tolxdorff-Neutzling, R.M., Wiedemann, B. (1985). Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrobial Agents Chemotherapy, 28, 302–307. https://doi.org/10.1128/aac.28.2.302
Knothe, H., Shah, P., Krcmery, V., Antal, M., Mitsuhashi S. (1983). Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection, 11, 315–317. https://doi.org/10.1007/BF01641355
Kurittu, P., Khakipoor, B., Jalava, J., Karhukorpi, J., Heikinheimo, A. (2022). Whole-genome sequencing of extended-spectrum Beta-Lactamase-producing Escherichia coli from human infections in Finland revealed isolates belonging to internationally successful ST131-C1-M27 subclade but distinct from non-human sources. Frontiers in Microbiology, 4(12), 789280. https://doi.org/10.3389/fmicb.2021.789280.
Liakopoulos, A., Mevius, D., Ceccarelli, D. (2016). A review of SHV extended-spectrum β-Lactamases: neglected yet ubiquitous. Frontiers in Microbiology, 7, 1374. https://doi.org/10.3389/fmicb.2016.01374
Liu, P., Li, P., Jiang, X. Bi. D., Xie, Y., Tai, C., Deng, Z., Rajakumar, K., Ou, H.Y. (2012). Complete genome sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a multidrug-resistant strain isolated from human sputum. Journal of Bacteriology, 194(7), 1841–1842. https://doi.org/10.1128/JB.00043-12
Livermore, D.M. (1995). Beta-Lactamases in laboratory and clinical resistance. Clinical Microbiology Reviews, 8, 557–584. https://doi.org/10.1128/CMR.8.4.557
Mammeri, H., Van De Loo, M., Poirel, L., Martinez-Martinez, L., Nordmann, P. (2005). Emergence of plasmid-mediated quinolone resistance in Escherichia coli in Europe. Antimicrobial Agents Chemotherapy, 49, 71–76. https://doi.org/10.1128/AAC.49.1.71-76.2005
Marcade, G., Deschamps, C., Boyd, A., Gautier, V., Picard, B., Branger, C., Denamur, E., Arlet, G. (2009). Replicon typing of plasmids in Escherichia coli producing extended-spectrum β-lactamases. Journal of Antimicrobial Chemotherapy, 63(1), 67–71. https://doi.org/10.1093/jac/dkn428
Miró., E., Navarro, F., Mirelis, B., Sabaté, M., Rivera, A., Coll, P., Prats, G. (2002). Prevalence of clinical isolates of Escherichia coli producing inhibitor-resistant β-Lactamases at a University Hospital in Barcelona, Spain, over a 3-year period. Antimicrobial Agents and Chemotherapy, 46(12), 3991–3994. https://doi.org/10.1128/AAC.46.12.3991-3994.2002
Mulani, M.S., Kamble, E.E., Kumkar, S.N. Tawre, M.S., Pardesi, K.R. (2019). Emerging strategies to combat ESKAPE pathogens in the era of antimicrobial resistance: a review. Frontiers in Microbiology, 10, 539. https://doi.org/10.3389/fmicb.2019.00539
Mulvey, M., Soule, G., Boyd, D., Demczuk, W., Ahmed, R. (2003). Characterization of the first extended-spectrum Beta-Lactamase-producing Salmonella isolate identified in Canada. Journal of Clinical Microbiology, 41(1), 460–462. https://doi.org/10.1128/JCM.41.1.460-462.2003
Novais, A., Canton, R., Moreira, R., Peixe, L., Baquero, F., Coque, T.M.(2007). Emergence and dissemination of Enterobacteriaceae isolates producing CTX-M-1- like enzymes in Spain are associated with IncFII (CTX-M-15) and broadhostrange (CTX-M-1, -3, and -32) plasmids. Antimicrobial Agents and Chemotherapy, 51, 796–799. https://doi.org/10.1128/AAC.01070-06
Nowakowska, M., Rogala-Zawada, D., Wiechuła, B. (2004). Czynniki etiologiczne zakażeń układu moczowego u dzieci i ich wrażliwość na antybiotyki. Wiadomości Lekarskie, 57, 438–443. [In Polish]
Ong, C.-L.Y., Ulett, G.C., Mabbett, A.N., Beatson, S.A., Webb, R.I., Monaghan, W., Nimmo, G.R., Looke, D.F., Mcewan, A.G., Schembri, M.A. (2008). Identyfication of Type 3 fimbriae in uropathogenic Escherichia coli reveals a role in biofilm formation. Journal of Bacteriology, 190(3), 1054–1063. https://doi.org/10.1128/JB.01523-07
Pagani, L., Dell’Amico, E., Migliavacca, R., D’Andrea, M.M., Giacobone, E., Amicosante, G., Romero, E., Rossolini, G.M. (2003). Multiple CTX-M-type extended-spectrum β-lactamases in nosomical isolates of Enterobacteriaceae from a hospital in Nor- thern Italy. Journal of Clinical Microbiology, 41(9), 4264–4269. https://doi.org/10.1128/JCM.41.9.4264-4269.2003
Paterson, D.L., Bonomo, R.A. (2005). Extended-spectrum β-lactamases: a clinical update. Clinical Microbiology, 18, 657–686. https://doi.org/10.1128/CMR.18.4.657-686.2005
Paterson, D.L., Ko, W.C., Von, Gottberg, A., Casellas, J.M., Mulazimoglu, L., Klugman, K.P., Bonomo, R.A., Rice, L.B., McCormack, J.G., Yu, V.L. (2001). Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum β-lactamases: implications for the clinical microbiology laboratory. Journal of Clinical Microbiology, 39, 2206–2212. https://doi.org/10.1128/JCM.39.6.2206-2212.2001
Pfaller, M.A, Jones, R.N, Doern, G.V. (1998). Bacterial Pathogens Isolated from Patients with Bloodstream Infection: Frequencies of Occurrence and Antimicrobial Susceptibility Patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). Antimicrobial Agents and Chemotherapy, 42, 1762–1770. https://doi.org/10.1128/AAC.42.7.1762
Pilonieta, M.C., Erickson, K.D., Ernst, R.K., Detweiler, C.S. (2009). A protein important for antimicrobial peptide resistance, YdeI/OmdA, is in the periplasm and interacts with OmpD/NmpC. Journal of Bacteriology, 191, 7243–7252. https://doi.org/10.1128/JB.00688-09
Pulzova, L., Navratilova, L., Comor, L. (2017). Alterations in outer membrane permeability favor drug- resistant phenotype of Klebsiella pneumoniae. Microbial Drug Resistance, 23(4), 413–420. https://doi.org/10.1089/mdr.2016.0017
Quentin, C., Arpin, C., Dubois, V., André, C., Lagrange, I., Fischer, I., Brochet, J.P., Grobost, F., Jullin, J., Dutilh, B., Larribet, G., Noury, P. (2004). Antibiotic resistance rates and phenotypes among isolates of Enterobacteriaceae in French extra-hospital practice. European Journal of Clinical Microbiology Infectious Diseases, 23, 185–193. https://doi.org/10.1007/s10096-003-1081-5
Radosz-Komoniewska, H., Gniadkowski, M., Rogala-Zawada, D., Nowakowska, M., Rudy, M., Wiechuła, B., Martirosian, G. (2004). Incidence of extender spectrum β-lactamases in clinical isolates of the family Enterobacteriaceae in pediatric hospital. Polish Journal of Microbiology, 53(1), 27–34.
Rudnicka, J., Wróblewska, M., Marchel, H. (2005). Częstość występowania i lekooporność pałeczek z rodziny Enterobacteriaceae izolowanych od pacjentów hospitalizowanych na oddziałach intensywnej terapii. Medycyna Doświadczalna i Mikrobiologia, 57, 185–191. [In Polish]
Sacha, P., Jakoniuk, P., Wieczorek, P. (2007). Mechanizmy oporności na antybiotyki β-laktamowe izolatów Escherichia coli, Klebsiella pneumoniae, Proteus mirabilit i Enterobacter cloacae opornych na cefotaksym. Wiadomości Lekarskie, 76, 314–321. [In Polish]
Sękowska, A., Wróblewska, J., Gospodarek., E. (2008). ESBL-dodatnie i ESBL-ujemne szczepy Klebsiella pneumoniae i Klebsiella oxytoca – występowanie w materiale klinicznym i wrażliwość na wybrane antybiotyki. Medycyna Doświadczalna i Mikrobiologia, 60, 39–44 [In Polish]
Wang, S., Wang, S., Tang, Y., Peng, G., Hao, T., Wu, X., Wei, J., Qiu, X., Zhou, D., Zhu, S. (2023). Detection of Klebsiella pneumonia DNA and ESBL positive strains by PCR-based CRISPR-LbCas12a system. Frontiers in Microbiology, 14, 1128261. https://doi.org/10.3389/fmicb.2023.1128261
Wolinowska, R., Masny, A., Płucienniczak, A. (2002). Integrony. Kosmos, 3, 353–364. [In Polish]
Zboromyrska, Y., Rico, V., Pitart, C., Fernández-Pittol, M.J., Soriano, Á., Bosch, J. (2022). Implementation of a New Protocol for Direct Identification from Urine in the Routine Microbiological Diagnosis. Antibiotics (Basel), 11(5), 582. https://doi.org/10.3390/antibiotics11050582
Zientara, M., Rudy, M., Samulska, E. (2008). Ocena wyników posiewów krwi dzieci leczonych w Górnośląskim Centrum Zdrowia Dziecka i Matki. Medycyna Doświadczalna i Mikrobiologia, 60, 65–69. [In Polish]
