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Molecular Characterization and In Silico Functional Insights into Carbapenem Resistance in Clinical Klebsiella pneumoniae Isolates from Al-Diwaniyah, Iraq.

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Τίτλος: Molecular Characterization and In Silico Functional Insights into Carbapenem Resistance in Clinical Klebsiella pneumoniae Isolates from Al-Diwaniyah, Iraq.
Συγγραφείς: Fairooz NA; Diwaniyah Technical Institute, AL-Furat AL-Awsat Technical University, Najaf 54003, Iraq., Ben Hassena A; Laboratory of Electrochemistry and Environment, National School of Engineers of Sfax, University of Sfax, BP 1173, Sfax 3038, Tunisia., Al Khalidi BA; College of Nursing, University of Al-Qadisiyah, Al-Diwaniyah 58001, Iraq., Aytar EC; Department of Horticulture, Faculty of Agriculture, Usak University, Uşak 64200, Türkiye., Aifa MS; Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, Sfax 3018, Tunisia., Hmani M; Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Sfax 3000, Tunisia.
Πηγή: Pathogens (Basel, Switzerland) [Pathogens] 2026 Aug 03; Vol. 15 (8). Date of Electronic Publication: 2026 Aug 03.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101596317 Publication Model: Electronic Cited Medium: Internet ISSN: 2076-0817 (Electronic) Linking ISSN: 20760817 NLM ISO Abbreviation: Pathogens Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI AG, 2012-
Ιατρικοί όροι (MeSH): Klebsiella pneumoniae*/drug effects , Klebsiella pneumoniae*/genetics , Klebsiella pneumoniae*/isolation & purification , Klebsiella Infections*/microbiology , Klebsiella Infections*/epidemiology , Anti-Bacterial Agents*/pharmacology , Carbapenems*/pharmacology, Iraq/epidemiology ; beta-Lactamases/genetics ; beta-Lactamases/chemistry ; beta-Lactamases/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Humans ; Microbial Sensitivity Tests ; Cross-Sectional Studies ; Mutation ; Molecular Docking Simulation ; Drug Resistance, Multiple, Bacterial ; Computer Simulation
Περίληψη: Background: The spread of extended-spectrum β-lactamase-producing Klebsiella is an emerging public health concern presenting severe clinical impacts. This problem is particularly severe in developing countries where irrational use of antibiotics makes the treatment of such infections more challenging. Methods: In this cross-sectional study, we investigated antibiotic resistance among clinical Klebsiella pneumoniae isolates from 256 patient specimens from Al-Diwaniyah hospitals, using standard microbiological methods followed by PCR. Antimicrobial susceptibility testing identified resistance rates and proportions of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Carbapenemase genes were detected by multiplex PCR and sequencing. Mutations were characterized, and their functional significance was predicted using in silico prediction tools. Results: Fifty Klebsiella pneumoniae isolates were recovered, exhibiting high resistance rates (42-100%) to penicillins, cephalosporins, fluoroquinolones and carbapenems, with 62% classified as MDR and 38% as XDR. Carbapenemase genes were highly prevalent (blaOXA-48 56%, blaIMP 44%, blaVIM 30%, blaKPC 28%, blaNDM 26%), with 60% of isolates co-harbouring ≥ two genes. Most mutations were predicted to be structurally tolerated, while active-site-proximal substitutions (H120L in NDM-52 and V120L in OXA-48) were predicted to affect enzyme activity. However, docking analysis suggested no significant alteration in carbapenem binding affinity. Conclusions: Our results highlight a very high prevalence of MDR/XDR Klebsiella pneumoniae, associated with diverse carbapenemase genes and resistance-related polymorphisms that may indicate potential functional impacts. To the best of our knowledge, this is the first study in Iraq to combine carbapenemase gene mutation analysis with structural modelling and molecular docking. This study emphasizes the urgent need for effective antimicrobial resistance surveillance in Iraq.
References: Osong Public Health Res Perspect. 2022 Dec;13(6):407-423. (PMID: 36617547)
J Antimicrob Chemother. 2013 Mar;68(3):487-9. (PMID: 23104494)
J Antimicrob Chemother. 2022 Aug 25;77(9):2429-2436. (PMID: 35815680)
Exp Ther Med. 2020 Apr;19(4):2449-2456. (PMID: 32256721)
Lancet Microbe. 2024 Aug;5(8):100854. (PMID: 38582098)
Virulence. 2017 May 19;8(4):460-469. (PMID: 27593176)
mSphere. 2019 Mar 27;4(2):. (PMID: 30918055)
Jundishapur J Microbiol. 2016 Mar 05;9(9):e19552. (PMID: 27942366)
PLoS One. 2015 Apr 20;10(4):e0123219. (PMID: 25893665)
Ann Clin Microbiol Antimicrob. 2021 Feb 15;20(1):13. (PMID: 33588850)
J Mol Biol. 2019 Mar 15;431(6):1172-1185. (PMID: 30769117)
Front Microbiol. 2023 Aug 28;14:1253160. (PMID: 37700870)
Antimicrob Agents Chemother. 2021 Mar 18;65(4):. (PMID: 33468463)
J Biol Chem. 2018 Aug 10;293(32):12606-12618. (PMID: 29909397)
Jundishapur J Microbiol. 2016 Mar 12;9(3):e31179. (PMID: 27226874)
Sci Rep. 2024 Jul 15;14(1):16333. (PMID: 39009596)
Infect Control Hosp Epidemiol. 2014 Apr;35(4):426-9. (PMID: 24602950)
Antibiotics (Basel). 2014 Jul 1;3(3):285-316. (PMID: 25364574)
Afr Health Sci. 2021 Jun;21(2):489-496. (PMID: 34795700)
Am J Clin Pathol. 1966 Apr;45(4):493-6. (PMID: 5325707)
Front Microbiol. 2016 Jun 13;7:895. (PMID: 27379038)
J Clin Microbiol. 2014 Dec;52(12):4377-80. (PMID: 25275000)
GMS Hyg Infect Control. 2014 Mar 07;9(1):Doc07. (PMID: 24653971)
Antimicrob Resist Infect Control. 2021 Mar 18;10(1):57. (PMID: 33736698)
Microorganisms. 2024 Dec 11;12(12):. (PMID: 39770751)
Antimicrob Agents Chemother. 2000 Nov;44(11):3003-7. (PMID: 11036013)
Front Cell Infect Microbiol. 2017 Nov 21;7:483. (PMID: 29209595)
J Antimicrob Chemother. 2012 Jul;67(7):1597-606. (PMID: 22499996)
Nucleic Acids Res. 2003 Jul 1;31(13):3784-8. (PMID: 12824418)
Front Cell Infect Microbiol. 2021 Sep 01;11:738223. (PMID: 34540722)
Antimicrob Agents Chemother. 2017 Dec 21;62(1):. (PMID: 29038264)
Nat Catal. 2024;7(5):499-509. (PMID: 38828429)
J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576)
Infect Drug Resist. 2025 Mar 25;18:1611-1628. (PMID: 40162036)
Microorganisms. 2022 Jan 24;10(2):. (PMID: 35208713)
Antimicrob Agents Chemother. 2004 Jan;48(1):15-22. (PMID: 14693513)
Indian J Med Microbiol. 2024 Nov-Dec;52:100736. (PMID: 39357832)
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20605-10. (PMID: 19098096)
Eur J Clin Microbiol Infect Dis. 2020 Jul;39(7):1287-1294. (PMID: 32124106)
Infect Drug Resist. 2023 Apr 13;16:2191-2201. (PMID: 37077254)
J Zhejiang Univ Sci B. 2013 Sep;14(9):837-43. (PMID: 24009204)
Infect Dis Ther. 2021 Mar;10(1):75-92. (PMID: 33492641)
Am J Med. 2006 Jun;119(6 Suppl 1):S3-10; discussion S62-70. (PMID: 16735149)
Emerg Infect Dis. 2018 Feb;24(2):221-229. (PMID: 29350134)
Infect Drug Resist. 2024 Mar 19;17:1107-1119. (PMID: 38525477)
J Antimicrob Chemother. 2015 Feb;70(2):463-9. (PMID: 25324420)
Gut Microbes. 2020 Sep 2;11(5):1287-1299. (PMID: 32404021)
Pathogens. 2022 May 05;11(5):. (PMID: 35631066)
Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0029725. (PMID: 40488615)
Elife. 2020 Jun 08;9:. (PMID: 32510322)
Front Microbiol. 2019 Jan 22;9:3198. (PMID: 30723463)
Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0044722. (PMID: 35980232)
Biomol Biomed. 2024 Sep 06;24(5):1178-1185. (PMID: 38696542)
ACS Infect Dis. 2020 May 8;6(5):1032-1043. (PMID: 32156115)
J Mol Biol. 1990 Oct 5;215(3):403-10. (PMID: 2231712)
Future Sci OA. 2020 Jan 27;6(3):FSO438. (PMID: 32140243)
Heliyon. 2025 Jan 31;11(3):e42419. (PMID: 39981361)
J Med Microbiol. 2018 Jul;67(7):957-964. (PMID: 29873627)
Contributed Indexing: Keywords: Al-Diwaniyah; Iraq; Klebsiella pneumoniae; MDR; XDR; antimicrobial resistance; carbapenem-resistant; carbapenemase genes; genetic diversity; mutation analysis
Substance Nomenclature: EC 3.5.2.6 (beta-Lactamases)
0 (Bacterial Proteins)
0 (Anti-Bacterial Agents)
0 (Carbapenems)
EC 3.5.2.6 (carbapenemase)
Entry Date(s): Date Created: 20260827 Date Completed: 20260827 Latest Revision: 20260829
Update Code: 20260829
PubMed Central ID: PMC13516738
DOI: 10.3390/pathogens15080819
PMID: 42654756
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2076-0817
DOI:10.3390/pathogens15080819