CRISPR-Cas system in multi drugs resistant Klebsiella pneumoniae from different clinical samples and its correlation with antibiotic-resistant genes in Mosul city / Iraq
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Abstract
Clustered, regularly interspaced short palindromic repeats (CRISPRs) and their related genes (Cas) are prevalent in the genomes of several bacteria and serve as a defense mechanism against external attackers, such as plasmids and viruses. This study aimed to examine the frequency of the CRISPR/Cas system in naturally occurring strains of Klebsiella pneumoniae sub spp pneumoniae confirmed by Vitek 2 biochemical test, in the hospital setting and determine its correlation with antibiotic resistance both phenotypically and genetically (antibiotic-resistant genes, namely blaTEM and AcrA efflux pump gene). The research was conducted at Medical College/ Mosul University 23 multi-drug resistant K. pneumoniae sub spp. pneumoniae that were obtained from 230 clinical samples from infected patients with different types of infections attending Al-Salam and Al-Jumhoree Teaching hospitals. PCR was used to detect blaTEM, AcrA genes, and CRISPR/Cas system genes (CAS1A and CAS1B) among the clinical isolates. The correlation between the CRISPR/Cas system and antibiotic-resistance was determined. All the isolates were multiple drug-resistant strains, and the blaTEM gene was detected in all clinical isolates, whereas AcrA gene was detected in 94% of the isolates. The frequency of CAS1A and CAS1B was 21.73% and 86.95% respectively. There was an inverse correlation between the CAS1A gene and phenotypic antibiotic resistance Disc diffusion test results, so isolates carrying CAS1A gene were less resistant to different antibiotics studied in this research. In contrast, there was no significant correlation between CRISPR / Cas genes, blaTEM, and AcrA genes at the genetic level.
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Keywords
blaTEM gene, CRISPR / Cas genes, Klebsiella pneumoniae sub spp. pneumoniae
References
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Alkompoz, A.K., Hamed, S.M., Zaid, A.S.A., Almangour, T.A., Al-Agamy, M.H. & Aboshanab, K.M. (2023). Correlation of CRISPR/Cas and Antimicrobial Resistance in Klebsiella pneumoniae Clinical Isolates Recovered from Patients in Egypt Compared to Global Strains. Microorganisms, 11(8), 1948. https://doi.org/10.3390/microorganisms11081948
Al-Saady, O. M. F. (2023). The effect of Ag- nanoparticles on Klebsiella pneumoniae biofilm formation and virulence genes. Ph. D. Thesis Biology / Microbiology.
Basgall, E.M., Goetting, S.C. & Goeckel, M.E. (2018). Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae. Microbiology. 164(4), 464–474. doi: 10.1099/mic.0.000635
Brooker, R.J. (2018). Genetics analysis and principle. 6th edition. University of Minnesota. New York NY : McGraw-Hill Education.
Carvalho I., Carvalho J.A. & Martínez-Álvarez S. (2021). Characterization of ESBL- Producing Escherichia coli and Klebsiella pneumoniae isolated from clinical samples in a Northern Portuguese Hospital: Predominance of CTX-M-15 and high genetic diversity. Microorganisms, 9(9), 1914. doi:10.3390/microorganisms9091914
CLSI (2022 ). Performance standards for antimicrobial susceptibility testing. 32th ed. CLSI supplement. M100. https://clsi.org/media/wi0pmpke/m100ed32_sample.pdf
Dirar, M.H., Bilal, N.E., Ibrahim, M.E. & Hamid, M.E. (2020). Prevalence of extended- spectrum β-lactamase (ESBL) and molecular detection of blaTEM, blaSHV and blaCTX-M genotypes among Enterobacteriaceae isolates from patients in Khartoum, Sudan. Pan Afr Med J, 37, 213. Published 2020 Nov 3. doi:10.11604 /pamj. 2020 .37.213 .24988
Efah, C.Y., Sun, T., Liu, S. & Wu, Y. (2020). Klebsiella pneumoniae: an increasing threat to public health. Annals of Clinical Microbiology and Antimicrobial, 30, 112-113. https://doi.org/10.1186/s12941-019-0343-8
Farhadi, M., Ahanjan, M. & Goli, H.R. (2021). High frequency of multidrug-resistant (MDR) Klebsiella pneumoniae harboring several β-lactamase and integron genes collected from several hospitals in the north of Iran. Ann Clin Microbiol Antimicrob, 20,70. https://doi.org/10.1186/s12941-021-00476-1
Farrag, H.A., Abdallah, N., Shehata, M.M.K. & Awad, E.M. (2019). Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria. J Biomed. Sci., 26(1), 69. doi:10.1186/s12929-019-0561-6
Guo, T.W., Bartesaghi, A. & Yang, H. (2017). Cryo-EM structures reveal mechanism and inhibition of DNA targeting by a CRISPR-Cas surveillance complex. Cell. 171(2), 414–426.e12. doi: 10.1016/j.cell.2017.09.006
Hille, F., Richter, H., Wong, S.P., Bratovič, M., Ressel, S. & Charpentier, E. (2018). The Biology of CRISPR-Cas: Backward and forward. Cell. 172, 6, 1239-1259, ISSN 0092-8674.https://doi.org/10.1016/j.cell.2017.11.032.
Ishino, Y., Krupovic, M. & Forterre, P. (2018). History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology. J Bacteriol. 200(7), e00580-17. Published 2018 Mar 12. doi:10.1128/JB.00580-17
Jwair, N.A., Al-Ouqaili, M.T.S. & Al-Marzooq, F. (2023). Inverse Association between the Existence of CRISPR/Cas Systems with Antibiotic Resistance, Extended Spectrum β-Lactamase and Carbapenemase Production in multidrug, extensive drug and pandrug-resistant Klebsiella pneumoniae. Antibiotics (Basel). 29, 12(6), 980. doi: 10.3390/antibiotics12060980. PMID: 37370299; PM
Karimi ,K., Zarei, O., Sedighi, P., Taheri, M., Doosti-Irani, A. & Shokoohizadeh, L. (2021). Investigation of Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Klebsiella pneumoniae. Int J Microbiol, 14, 2021, 5573388. doi: 10.1155/2021/5573388. PMID: 34221021; PMCID: PMC8219462.
Kashefieh, M., Hosainzadegan, H., Baghbanijavid, S. & Ghotaslou, R. (2021). The Molecular Epidemiology of Resistance to Antibiotics among Klebsiella pneumoniae Isolates in Azerbaijan. Iran. J Trop Med. 2021, 9195184. doi:10.1155/2021/9195184CID: PMC10295211.
Kamruzzaman, M. & Iredell, J.R. (2020). CRISPR-Cas system in antibiotic resistance plasmids in Klebsiella pneumoniae. Front. Microbiol., 10, 2934. https://doi.org/10.3389/fmicb.2019.02934
Khalid, T. M., & Ghaima, K. K. (2022). Molecular Detection of acrAB and oqxAB Genes in Klebsiella pneumoniae and evaluation of the Effect of Berberine on their Gene Expression. Iraqi Journal of Biotechnology, 21(2), 124–135.
Li, H.Y., Kao, C.Y, Lin, W.H., Zheng, P.X., Yan, J.J., Wang, M.C., Teng, C.H., Tseng, C.C. & Wu, J.J. (2018). Characterization of CRISPR-Cas Systems in Clinical Klebsiella pneumoniae isolates uncovers its potential association with antibiotic susceptibility. Front. Microbiol., 9, 1595.https://doi.org/10.3389/fmicb.2018.01595.
Liao, W., Liu, Y., Chen, C., Li, J., Du, F., Long, D. & Zhang, W. (2020). Distribution of CRISPR-Cas Systems in Clinical Carbapenem-Resistant Klebsiella pneumoniae Strains in a Chinese Tertiary Hospital and Its Potential Relationship with Virulence. Microb. Drug Resist. 26, 630–636. doi:10.1089/mdr.2019.0276
Makarova, K.S. & Koonin, E. V. (2015). Annotation and Classification of CRISPR- Cas Systems. Methods Mol Biol. 1311, 47–75. doi:10.1007/978-1-4939-2687-9
Makarova, K.S, Zhang, F.& Koonin, E.V. (2017). Snap Shot: class 2 CRISPR-Cas systems. Cell. 168(1), 328–8. doi: 10.1016/j.cell.2016.12.038
Makarova, K.S., Wolf, Y. I. & Koonin, E.V. (2018). Classification and Nomenclature of CRISPR-Cas Systems: Where from here? CRISPR J. 1(5), 325-336. doi: 10.1089/crispr.2018.0033. PMID: 31021272; PMCID: PMC6636873.
Medina-Aparicio, L., Davila, S., Rebollar-Flores, J.E., Calva, E. & Hernandez-Lucas, I. (2018). The CRISPR-Cas system in Enterobacteriaceae. Pathog. Dis., 76. doi: 10.1093/femspd/fty002.
Moghadas, A.J., Kalantari, F., Sarfi, M., Shahhoseini, S. & Mirkalantari, S. (2018). Evaluation of virulence factors and antibiotic resistance patterns in clinical urine isolates of Klebsiella pneumoniae in Semnan, Iran. Jundishapur. J Microbiol, 11(7), 1–6. https://doi.org/10.5812/jjm.63637.
Naqid, I. A., Hussein, N. R., Balatay, A. A., Saeed, K. A. & Ahmed, H. A. (2020). The Antimicrobial resistance pattern of Klebsiella pneumonia Isolated from the Clinical Specimens in Duhok City in Kurdistan Region of Iraq. Journal of Kermanshah University of Medical Sciences, 24(2). https://doi.org/10.5812/jkums.106135.
Nawaz S., Riaz, S. & Hasnain, S. (2009). Screening methicillin resistant Staphylococcus aureus (MRSA) bacteriocin producing bacteria. African Journal of Biotechnology, 8, 365–8. http://www.academicjournals.org/AJB ISSN 1684–5315 © 2009 Academic Journals
Newsom, S., Parameshwaran, H.P., Martin L. & Rajan, R.(2020). The CRISPR-Cas Mechanism for adaptive immunity and alternate Bacterial Functions Fuels Diverse Biotechnologies. Front. Cell. Infect. Microbiol., Sec. Molecular Bacterial Pathogenesis, 10 . https://doi.org/10.3389/fcimb.2020.619763.
Odari, R. & Dwadi, P. (2022). Prevalence of multidrug-resistant Klebsiella pneumoniae clinical isolates in Nepal. J. Trop Med., 12. https://doi.org/10.1155/2022/5309350
Pishtiwan, A.H. & Khadija, K.M. (2019) Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia patients in Erbil, Iraq. Mediterr J Hematol Infect Dis. 11(1):e2019041. Published 2019 Jul 1. doi:10.4084/MJHID.2019.041
Ragupathi, N.K.D. (2020). The Influence of biofilms on carbapenem susceptibility and patient outcome in device Associated Klebsiella pneumoniae infections: Insights Into phenotype vs genome-wide analysis and correlation. Front Microbiol. 11, 591679. https://doi.org/10.3389/fmicb.2020.591679
Raouf, F. E. A., Benyagoub, E., Alkhudhairy, M. K., Akrami, S. & Saki, M. (2022). Extended-spectrum beta-lactamases among Klebsiella pneumoniae from Iraqi patients with community-acquired pneumonia. Revista Da Associacao Medica Brasileira, 68(6), 833–837. https://doi.org/10.1590/1806-9282.20220222
Sewunet, T., Asrat, D. & Woldeamanuel, Y. (2021). High prevalence of blaCTX-M and nosocomial transmission of hypervirulent epidemic clones of Klebsiella pneumoniae at a tertiary hospital in Ethiopia. JAC Antimicrob Resist., 3(1), dlab001. Published 2021 Feb 3. doi:10.1093/jacamr/dlab001
Shabbir, M.A., Wu, Q., Shabbir, M.Z., Sajid, A., Ahmed, S., Sattar, A., Tang, Y., Li, J., Maan, M.K. & Hao, H. (2018). The CRISPR-cas system promotes antimicrobial resistance in Campylobacter jejuni. Future Microbiol, 13, 1757–1774. doi: 10.2217/fmb-2018-0234. Epub 2018 Dec 11.
Szabo, O., Kocsis, B., Szabo, N., Kristof, K. & Szabo, D. (2018). Contribution of OqxABEfflux Pump in selection of fluoroquinolone-resistant Klebsiella pneumoniae. Canadian Journal Infectious Diseases Medical Microbiology, 23, 4271638. doi:10.1155/2018/4271638.
Tao, S., Chen, H., Li, N., Wang, T. & Liang, W. (2022). The Spread of Antibiotic Resistance Genes In Vivo Model. Can J Infect Dis Med Microbiol. 18, 2022, 3348695. doi: 10.1155/2022/3348695.
Touchon, M., Charpentier, S., Pognard, D., Picard, B., Arlet, G., Rocha, E.P., Denamur, E. & Branger, C. (2012). Antibiotic resistance plasmids spread among natural isolates of Escherichia coli in spite of CRISPR elements. Microbiology , 158, 2997–3004. doi:10.1099/mic.0.06 0814-0
Vaez, H., Sahebkar, A. & Khademi, F. (2019). Carbapenem-Resistant Klebsiella pneumoniae in Iran: a systematic review and meta-analysis. J Chemother.,31(1), 1–8. doi: 10.1080/1120009X.2018.1533266.
Wang, C., Yuan, Z., Huang, W., Yan, L., Tang, J. & Liu, C. (2019). Epidemiologic analysis and control strategy of Klebsiella pneumoniae infection in intensive care units in a teaching hospital of People’s Republic of China. Infect Drug Resist, 12, 391–398, Feb. 2019. doi: 10.2147/IDR.S189154.
Wang, G., Song, G. & Xu, Y. (2020). Association of CRISPR/Cas System with the Drug Resistance in Klebsiella pneumoniae. Infect. Drug Resist.,13,1929–1935. doi:10.2147/IDR.S253380.
Wasfi, R., Elkhatib, W.F. & Ashour, H.M. (2016). Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep., 22, 6, 38929. doi: 10.1038/srep38929.
Zhu, W., Tian, Y., Xiang, L., Cao, L.. & He, L. (2023). A case of multidrug-Resistant Klebsiella pneumoniae treated with carrimycin. Infect Drug Resist., 16, 2365-2369. doi:10.2147/IDR.S407076.
Al-Garni, S. M., Ghonaim, M. M., Ahmed, M. M. M., Al-Ghamdi, A. S. & Ganai, F. A. (2018). Risk factors and molecular features of extended-spectrum beta-lactamase producing bacteria at southwest of Saudi Arabia. Saudi Medical Journal. 39(12),1186–1194. https://doi.org/10.15537/smj.2018.12.23273
Alkompoz, A.K., Hamed, S.M., Zaid, A.S.A., Almangour, T.A., Al-Agamy, M.H. & Aboshanab, K.M. (2023). Correlation of CRISPR/Cas and Antimicrobial Resistance in Klebsiella pneumoniae Clinical Isolates Recovered from Patients in Egypt Compared to Global Strains. Microorganisms, 11(8), 1948. https://doi.org/10.3390/microorganisms11081948
Al-Saady, O. M. F. (2023). The effect of Ag- nanoparticles on Klebsiella pneumoniae biofilm formation and virulence genes. Ph. D. Thesis Biology / Microbiology.
Basgall, E.M., Goetting, S.C. & Goeckel, M.E. (2018). Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae. Microbiology. 164(4), 464–474. doi: 10.1099/mic.0.000635
Brooker, R.J. (2018). Genetics analysis and principle. 6th edition. University of Minnesota. New York NY : McGraw-Hill Education.
Carvalho I., Carvalho J.A. & Martínez-Álvarez S. (2021). Characterization of ESBL- Producing Escherichia coli and Klebsiella pneumoniae isolated from clinical samples in a Northern Portuguese Hospital: Predominance of CTX-M-15 and high genetic diversity. Microorganisms, 9(9), 1914. doi:10.3390/microorganisms9091914
CLSI (2022 ). Performance standards for antimicrobial susceptibility testing. 32th ed. CLSI supplement. M100. https://clsi.org/media/wi0pmpke/m100ed32_sample.pdf
Dirar, M.H., Bilal, N.E., Ibrahim, M.E. & Hamid, M.E. (2020). Prevalence of extended- spectrum β-lactamase (ESBL) and molecular detection of blaTEM, blaSHV and blaCTX-M genotypes among Enterobacteriaceae isolates from patients in Khartoum, Sudan. Pan Afr Med J, 37, 213. Published 2020 Nov 3. doi:10.11604 /pamj. 2020 .37.213 .24988
Efah, C.Y., Sun, T., Liu, S. & Wu, Y. (2020). Klebsiella pneumoniae: an increasing threat to public health. Annals of Clinical Microbiology and Antimicrobial, 30, 112-113. https://doi.org/10.1186/s12941-019-0343-8
Farhadi, M., Ahanjan, M. & Goli, H.R. (2021). High frequency of multidrug-resistant (MDR) Klebsiella pneumoniae harboring several β-lactamase and integron genes collected from several hospitals in the north of Iran. Ann Clin Microbiol Antimicrob, 20,70. https://doi.org/10.1186/s12941-021-00476-1
Farrag, H.A., Abdallah, N., Shehata, M.M.K. & Awad, E.M. (2019). Natural outer membrane permeabilizers boost antibiotic action against irradiated resistant bacteria. J Biomed. Sci., 26(1), 69. doi:10.1186/s12929-019-0561-6
Guo, T.W., Bartesaghi, A. & Yang, H. (2017). Cryo-EM structures reveal mechanism and inhibition of DNA targeting by a CRISPR-Cas surveillance complex. Cell. 171(2), 414–426.e12. doi: 10.1016/j.cell.2017.09.006
Hille, F., Richter, H., Wong, S.P., Bratovič, M., Ressel, S. & Charpentier, E. (2018). The Biology of CRISPR-Cas: Backward and forward. Cell. 172, 6, 1239-1259, ISSN 0092-8674.https://doi.org/10.1016/j.cell.2017.11.032.
Ishino, Y., Krupovic, M. & Forterre, P. (2018). History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology. J Bacteriol. 200(7), e00580-17. Published 2018 Mar 12. doi:10.1128/JB.00580-17
Jwair, N.A., Al-Ouqaili, M.T.S. & Al-Marzooq, F. (2023). Inverse Association between the Existence of CRISPR/Cas Systems with Antibiotic Resistance, Extended Spectrum β-Lactamase and Carbapenemase Production in multidrug, extensive drug and pandrug-resistant Klebsiella pneumoniae. Antibiotics (Basel). 29, 12(6), 980. doi: 10.3390/antibiotics12060980. PMID: 37370299; PM
Karimi ,K., Zarei, O., Sedighi, P., Taheri, M., Doosti-Irani, A. & Shokoohizadeh, L. (2021). Investigation of Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Klebsiella pneumoniae. Int J Microbiol, 14, 2021, 5573388. doi: 10.1155/2021/5573388. PMID: 34221021; PMCID: PMC8219462.
Kashefieh, M., Hosainzadegan, H., Baghbanijavid, S. & Ghotaslou, R. (2021). The Molecular Epidemiology of Resistance to Antibiotics among Klebsiella pneumoniae Isolates in Azerbaijan. Iran. J Trop Med. 2021, 9195184. doi:10.1155/2021/9195184CID: PMC10295211.
Kamruzzaman, M. & Iredell, J.R. (2020). CRISPR-Cas system in antibiotic resistance plasmids in Klebsiella pneumoniae. Front. Microbiol., 10, 2934. https://doi.org/10.3389/fmicb.2019.02934
Khalid, T. M., & Ghaima, K. K. (2022). Molecular Detection of acrAB and oqxAB Genes in Klebsiella pneumoniae and evaluation of the Effect of Berberine on their Gene Expression. Iraqi Journal of Biotechnology, 21(2), 124–135.
Li, H.Y., Kao, C.Y, Lin, W.H., Zheng, P.X., Yan, J.J., Wang, M.C., Teng, C.H., Tseng, C.C. & Wu, J.J. (2018). Characterization of CRISPR-Cas Systems in Clinical Klebsiella pneumoniae isolates uncovers its potential association with antibiotic susceptibility. Front. Microbiol., 9, 1595.https://doi.org/10.3389/fmicb.2018.01595.
Liao, W., Liu, Y., Chen, C., Li, J., Du, F., Long, D. & Zhang, W. (2020). Distribution of CRISPR-Cas Systems in Clinical Carbapenem-Resistant Klebsiella pneumoniae Strains in a Chinese Tertiary Hospital and Its Potential Relationship with Virulence. Microb. Drug Resist. 26, 630–636. doi:10.1089/mdr.2019.0276
Makarova, K.S. & Koonin, E. V. (2015). Annotation and Classification of CRISPR- Cas Systems. Methods Mol Biol. 1311, 47–75. doi:10.1007/978-1-4939-2687-9
Makarova, K.S, Zhang, F.& Koonin, E.V. (2017). Snap Shot: class 2 CRISPR-Cas systems. Cell. 168(1), 328–8. doi: 10.1016/j.cell.2016.12.038
Makarova, K.S., Wolf, Y. I. & Koonin, E.V. (2018). Classification and Nomenclature of CRISPR-Cas Systems: Where from here? CRISPR J. 1(5), 325-336. doi: 10.1089/crispr.2018.0033. PMID: 31021272; PMCID: PMC6636873.
Medina-Aparicio, L., Davila, S., Rebollar-Flores, J.E., Calva, E. & Hernandez-Lucas, I. (2018). The CRISPR-Cas system in Enterobacteriaceae. Pathog. Dis., 76. doi: 10.1093/femspd/fty002.
Moghadas, A.J., Kalantari, F., Sarfi, M., Shahhoseini, S. & Mirkalantari, S. (2018). Evaluation of virulence factors and antibiotic resistance patterns in clinical urine isolates of Klebsiella pneumoniae in Semnan, Iran. Jundishapur. J Microbiol, 11(7), 1–6. https://doi.org/10.5812/jjm.63637.
Naqid, I. A., Hussein, N. R., Balatay, A. A., Saeed, K. A. & Ahmed, H. A. (2020). The Antimicrobial resistance pattern of Klebsiella pneumonia Isolated from the Clinical Specimens in Duhok City in Kurdistan Region of Iraq. Journal of Kermanshah University of Medical Sciences, 24(2). https://doi.org/10.5812/jkums.106135.
Nawaz S., Riaz, S. & Hasnain, S. (2009). Screening methicillin resistant Staphylococcus aureus (MRSA) bacteriocin producing bacteria. African Journal of Biotechnology, 8, 365–8. http://www.academicjournals.org/AJB ISSN 1684–5315 © 2009 Academic Journals
Newsom, S., Parameshwaran, H.P., Martin L. & Rajan, R.(2020). The CRISPR-Cas Mechanism for adaptive immunity and alternate Bacterial Functions Fuels Diverse Biotechnologies. Front. Cell. Infect. Microbiol., Sec. Molecular Bacterial Pathogenesis, 10 . https://doi.org/10.3389/fcimb.2020.619763.
Odari, R. & Dwadi, P. (2022). Prevalence of multidrug-resistant Klebsiella pneumoniae clinical isolates in Nepal. J. Trop Med., 12. https://doi.org/10.1155/2022/5309350
Pishtiwan, A.H. & Khadija, K.M. (2019) Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia patients in Erbil, Iraq. Mediterr J Hematol Infect Dis. 11(1):e2019041. Published 2019 Jul 1. doi:10.4084/MJHID.2019.041
Ragupathi, N.K.D. (2020). The Influence of biofilms on carbapenem susceptibility and patient outcome in device Associated Klebsiella pneumoniae infections: Insights Into phenotype vs genome-wide analysis and correlation. Front Microbiol. 11, 591679. https://doi.org/10.3389/fmicb.2020.591679
Raouf, F. E. A., Benyagoub, E., Alkhudhairy, M. K., Akrami, S. & Saki, M. (2022). Extended-spectrum beta-lactamases among Klebsiella pneumoniae from Iraqi patients with community-acquired pneumonia. Revista Da Associacao Medica Brasileira, 68(6), 833–837. https://doi.org/10.1590/1806-9282.20220222
Sewunet, T., Asrat, D. & Woldeamanuel, Y. (2021). High prevalence of blaCTX-M and nosocomial transmission of hypervirulent epidemic clones of Klebsiella pneumoniae at a tertiary hospital in Ethiopia. JAC Antimicrob Resist., 3(1), dlab001. Published 2021 Feb 3. doi:10.1093/jacamr/dlab001
Shabbir, M.A., Wu, Q., Shabbir, M.Z., Sajid, A., Ahmed, S., Sattar, A., Tang, Y., Li, J., Maan, M.K. & Hao, H. (2018). The CRISPR-cas system promotes antimicrobial resistance in Campylobacter jejuni. Future Microbiol, 13, 1757–1774. doi: 10.2217/fmb-2018-0234. Epub 2018 Dec 11.
Szabo, O., Kocsis, B., Szabo, N., Kristof, K. & Szabo, D. (2018). Contribution of OqxABEfflux Pump in selection of fluoroquinolone-resistant Klebsiella pneumoniae. Canadian Journal Infectious Diseases Medical Microbiology, 23, 4271638. doi:10.1155/2018/4271638.
Tao, S., Chen, H., Li, N., Wang, T. & Liang, W. (2022). The Spread of Antibiotic Resistance Genes In Vivo Model. Can J Infect Dis Med Microbiol. 18, 2022, 3348695. doi: 10.1155/2022/3348695.
Touchon, M., Charpentier, S., Pognard, D., Picard, B., Arlet, G., Rocha, E.P., Denamur, E. & Branger, C. (2012). Antibiotic resistance plasmids spread among natural isolates of Escherichia coli in spite of CRISPR elements. Microbiology , 158, 2997–3004. doi:10.1099/mic.0.06 0814-0
Vaez, H., Sahebkar, A. & Khademi, F. (2019). Carbapenem-Resistant Klebsiella pneumoniae in Iran: a systematic review and meta-analysis. J Chemother.,31(1), 1–8. doi: 10.1080/1120009X.2018.1533266.
Wang, C., Yuan, Z., Huang, W., Yan, L., Tang, J. & Liu, C. (2019). Epidemiologic analysis and control strategy of Klebsiella pneumoniae infection in intensive care units in a teaching hospital of People’s Republic of China. Infect Drug Resist, 12, 391–398, Feb. 2019. doi: 10.2147/IDR.S189154.
Wang, G., Song, G. & Xu, Y. (2020). Association of CRISPR/Cas System with the Drug Resistance in Klebsiella pneumoniae. Infect. Drug Resist.,13,1929–1935. doi:10.2147/IDR.S253380.
Wasfi, R., Elkhatib, W.F. & Ashour, H.M. (2016). Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals. Sci Rep., 22, 6, 38929. doi: 10.1038/srep38929.
Zhu, W., Tian, Y., Xiang, L., Cao, L.. & He, L. (2023). A case of multidrug-Resistant Klebsiella pneumoniae treated with carrimycin. Infect Drug Resist., 16, 2365-2369. doi:10.2147/IDR.S407076.
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How to Cite
CRISPR-Cas system in multi drugs resistant Klebsiella pneumoniae from different clinical samples and its correlation with antibiotic-resistant genes in Mosul city / Iraq. (2024). Journal of Applied and Natural Science, 16(2), 820-829. https://doi.org/10.31018/jans.v16i2.5529
