Skip to main content

Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca



Silybin and curcumin have potential antimicrobial effects. This study aimed to evaluate the synergistic antimicrobial effects of silybin and curcumin on virulence and carbapenemase genes expression among multidrug-resistant (MDR) Klebsiella oxytoca.


A total of 70 MDR K. oxytoca (carrying blaIMP and blaOXA-48-like genes) were included. The antibiotic susceptibility and biofilm production of isolates were determined. The silybin and curcumin at concentrations 10–500 mg/mL alone and in combination were exposed to bacterial isolates in Mueller Hinton broth medium for 24 h. The expression of blaIMP, blaOXA-48-like, mrkA, pilQ, matB and fimA genes was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR).

The mean minimum inhibitory concentration (MIC) of curcumin and silybin were 250 mg/mL and 500 mg/mL, respectively. The anti-virulent effect of 100 mg/mL of silybin and curcumin was shown by significant reduction in the expression of fimA (2.1-fold, P < 0.0001) and mrkA (2.1 fold, P < 0.0001) genes. Moreover, these compounds significantly decreased the expression of blaIMP1 (3.2-fold, P < 0.0001) gene. Notably, there was no significant effect on pilQ, matB and blaOXA-48-like genes. The results showed that silybin and curcumin can be candidate as natural way for control the MDR virulent strains of K. oxytoca.


Multidrug-resistant (MDR) Enterobacteriaceae members are causative agents of fatal nosocomial infections which have narrow or none therapeutic choices [1,2,3]. The evolution of carbapenemase-producing (CP) strains has limited last-line treatment resorts. These strains may develop the resistance through various mechanisms such as production of carbapenemase enzymes [2, 3]. Some of these enzymes include imipenemases (IMPs), OXA-type beta-lactamase, and New Delhi metallo-β-lactamase 1 (NDM-1) [4].

MDR Klebsiella oxytoca with resistance to carbapenems has been reported from various areas which encode carbapenemase genes [5, 6]. K. oxytoca strains are mostly opportunistic pathogens among immunocompromised patients [7]. Biofilm formation is another strategy of K. oxytoca for cell attachment and colonization. In K. oxytoca, fimA, mrkA, pilQ and matB play substantial role in bacterial attachment and colonization [3, 8]. FimA, MrkA and MatB are the major protein subunits of type 1 (fimBEAICDFGH operon), type 3 (mrkABCDF operon) and Mat fimbriae, respectively which recognized in uropathogenic Escherichia coli and can mediate adhesion and biofilm formation [9,10,11]. PilQ is one of the structural subunits of type IV pili (T4P) that is involved in several processes such as motility, biofilm formation, and DNA uptake [12].

One strategy to combat the infections caused by the virulent and drug-resistant bacteria is control of expression of thier genes. Hence, seeking to alternative approaches such as herbal medicine compounds contribute to efficient eradication of infections. Silybin is a multiple applicable herbal medicine compound and has antimicrobial properties [13]. Furthermore, curcumin is another herbal compound with vast properties [14,15,16]. The antimicrobial effects of curcumin have been determined previously [15, 16]. Also, combination anticancer therapies using curcumin-silybin has been demonstrated before [17].

Until today, there has not been any previous study regarding effect of curcumin and silybin on the virulence and carbapenemase genes expression. This study aimed to assess the effects of silybin and curcumin on virulence and carbapenemase genes expression among MDR K. oxytoca.

Main text

Materials and methods


This study was approved by the University of Mosul, Mosul, Iraq according to the Declaration of Helsinki. No human and animal data or sample were included in this study.

Clinical isolates

The flow chart of the employed procedures in the present study is shown in Additional file 1: Fig. S1 [18] to the readers at one glance. Herein, 70 MDR K. oxytoca isolates that collected from stool samples during 2012–2019 were included. The isolation and identification of K. oxytoca were performed using standard bacteriology tests including MacConkey agar (Merck, Germany), triple sugar iron agar, methyl red/Voges-Proskauer, and citrate and urea utilization as mentioned in Table 1 [19]. The antibiotic susceptibility pattern was determined using Kirby-Bauer method according to the Clinical and Laboratory Standards Institute (CLSI) 2017 [20]. The antibiotic discs included cefepime (30 μg), cefotaxime (30 μg), ceftazidime (30 μg), ciprofloxacin (5 μg), tetracycline (30 μg), amikacin (30 μg), piperacillin-tazobactam (100/10 μg), gentamicin (10 μg), imipenem (10 μg), meropenem (10 μg), and trimethoprim-sulfamethoxazole (1.25/23.75 μg) (Bioanalyse, Ankara, Turkey). Escherichia coli ATCC® 25922TM was used as quality control strain. Isolates that were resistant against three antibiotics in different classes were considered MDR [21]. All isolates carried the blaIMP, blaOXA-48-like, mrkA, pilQ, matB and fimA genes.

Table 1 Biochemical test results for Klebsiella oxytoca isolates

Curcumin and silybin antibacterial effects

Curcumin and silybin compounds were purchased from Sigma Aldrich, USA. Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione) is a yellow–orange lipophilic compound that dissolves in acetone, dimethylsulfoxide, and ethanol but is insoluble in water, acidic, and neutral solutions. This compound is an integral component of turmeric (Curcuma longa) (up to ~ 5%) [22]. This aromatic ginger family (Zingiberaceae) plant is native to southwestern and southern Asia [22]. It consists of two aromatic rings symmetrically substituted in ortho position with methoxy and phenolic OH groups. These 2 rings are joined to a seven-membered hydrocarbon chain with an enone portion and 1,3-diketone group [22]. For thousands of years, milk thistle (Silybum marianum) has been used as an herbal remedy for treating a variety of diseases [23]. Among the major components of S. marianum fruit extract (silymarin) is a flavanolignan called silybin, which is the most active principal constituent [23]. Molecular formula of silybin is C25H22O10 and its molecular weight is 482.441. It is also called silybine, flavobin, and silymarin I. In general, it is a highly functionalized small molecule with alternate carbo- and hetero-cycles [23]. There are two main units in the silybin structure: the first unit is based on a flavononol group in flavonoids, called taxifolin, and the second is conyferil alcohol, a phenyllpropanoid unit. An oxeran ring joins the two units together to form one structure [23]. Various concentrations (10–500 mg/mL) of both compounds were prepared and their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined according to previously described method [24]. The Mueller Hinton broth (MHB) medium (Merk, Germany) was employed. A bacterial suspension equal to 0.5 MacFarland turbidity was prepared and added to each dilution and incubated at 37 °C for 24 h. The MIC of a concentration was defined following observation of no growth and the MBC was defined for each dilution without growth of 100 µL of suspension onto the MHA medium [24]. Escherichia coli ATCC® 25922™ was used as quality control strain.

Biofilm formation

The biofilm formation was conducted using microtiter plate assay. A bacterial suspension was cultured into each well of 96-well plate containing trypticase soy broth (TSB) medium (Merck, Germany) and incubated for 24 h. The plates were washed and dried. The well attachments were fixed using methanol. The crystal violet was added and left for 15 min and washed again. Using ethanol, the bacterial attachments were made soluble and the opacity was measured using ELISA reader at OD490. The biofilm formation was defined compared to the control wells. There were four categories of isolates: non-biofilm producers (ODT < ODc), weak-biofilm producers (ODc < ODT < 2 × ODc), moderate-biofilm producers (2×ODc < ODT < 4 × ODc), and strong-biofilm producers (4 × ODc < ODT) [25].

RNA extraction and real-time polymerase chain reaction

The total RNA (Qiagen GmbH, Hilden, Germany) was extracted from 1 × 106 cells suspension of isolates and cDNA (Takara, Japan) was synthesized according to the manufacturers’ instructions. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed using specific primers represented in Table 2 and using CFX96 Touch Real-Time PCR Detection System (Bio-Rad, USA). The gyrA gene was considered as the reference of expression analysis (Table 2) [26]. The K. oxytoca ATCC® 43165™ was used as control strain.

Table 2 The sequence of primers used in this study

Statistical analysis

Chi Square and analysis of variance (ANOVA) tests were used with 95% confidence intervals to analyze the data using Statistical Package for the Social Sciences (SPSS) version 22.0 (IBM Corporation, Armonk, NY, USA). A P-value less than 0.05 was considered significant [8].


Antibiotic resistance

As shown in Table 3 and Additional file 2: Fig. S2, all isolates were resistant to ceftazidime, cefotaxime, imipenem, tetracycline and trimethoprim-sulfamethoxazole and considered MDR. Moreover, 98.6%, 90.0%, 90.0%, 81.4%, 80.0% and 80.0% of them were resistant to meropenem, piperacillin-tazobactam, amikacin, ciprofloxacin, cefepime, and gentamicin, respectively. The highest rate of susceptibility was to cefepime (20.0%).

Table 3 Antibiotic susceptibility of Klebsiella oxytoca isolates

Biofilm formation

Among 70 MDR K. oxytoca from stool samples, none of them produced strong-level biofilms and all were in moderate level (Additional file 3: Fig. S3).

Antibacterial effects

The mean MIC90 and MBC90 of curcumin were 250 mg/mL and > 250 mg/mL, respectively. Meanwhile, those of silybin included 500 mg/mL and > 500 mg/mL, respectively. All concentrations of both plants had antibacterial effects against MDR K. oxytoca isolates.

Gene expression

The calculation of expression levels was performed according to the 2−ΔΔCT. We observed that 100 mg/mL of curcumin and silybin could singly decrease the expression of fimA and mrkA genes, respectively (data not shown). None of other genes were significantly affected. The anti-virulent effect of 100 mg/mL of silybin and curcumin in combination was shown by decrease in the expression of fimA (2.1-fold, P < 0.0001) and mrkA (2.1 fold, P < 0.0001) genes (Additional file 4: Fig. S4). Moreover, these compounds decreased the expression of blaIMP1 (3.2-fold, P < 0.0001) gene. Notably, there was no significant effect on expression of pilQ, matB and blaOXA-48-like genes (Additional file 4: Fig. S4).


In this study, 70 MDR K. oxytoca isolates collected from stool samples during 2012–2019 were included. All isolates were resistant to ampicillin, ceftazidime, trimethoprim-sulfamethoxazole, imipenem and tetracycline. All isolates carried the blaIMP, blaOXA-48-like, mrkA, pilQ, matB and fimA genes. We observed that all of them were moderate biofilm producers possibly mediated by adhesins including mrkA, pilQ, matB and fimA genes. In line with the current study, Ghasemian et al. [5] from Iran reported high rate of adhesins among MDR and non-MDR K. oxytoca isolates during 2016–2017.

There is scarcity in data regarding effects of curcumin and silybin against expression of virulence and antibiotic resistance genes among K. oxytoca. Moreover, antimicrobial and anti-biofilm effects of curcumin and silymarin has been exhibited previously [15, 16, 27]. In this study, the mean MIC90 and MBC90 of curcumin were 250 mg/mL and > 250 mg/mL, respectively. Meanwhile, those of silybin were 500 mg/mL and > 500 mg/mL, respectively. In previous study by Adamczak et al. [15], Acinetobacter lwoffii (250 µg/mL), Streptococcus pyogenes (31.25 µg/mL), Pseudomonas aeruginosa and Enterococcus faecalis (62.5 g/mL), and methicillin-sensitive Staphylococcus aureus (250 µg/mL) were found to be susceptible to curcumin. In another study by Evren et al. [27], MIC and MBC values were between 60 and > 241 μg/mL and greater than 241 μg/mL, respectively. The inhibition of bacteria may be due to this fact that compounds derived from S. marianum and C. longa are known to exert profound antibacterial effects, mostly by inhibiting RNA and protein production, quorum sensing (QS) system, and targeting the cellular components [28, 29].

In this study, 100 mg/mL of curcumin and silybin could singly decrease the expression of fimA and mrkA genes, respectively. None of other genes were significantly affected. The anti-virulent effect of 100 mg/mL of silybin and curcumin in combination was shown by 2.1 fold reduction (P < 0.0001) in the expression of fimA and mrkA genes of MDR K. oxytoca compared to control strain. Moreover, these compounds reduced the expression of blaIMP1 gene. Notably, there was no significant effect on pilQ, matB and blaOXA-48-like genes. In an experiment by Eslami et al. [28], silymarin had no effect on blaIMP and blaOXA-48 expression in MDR E. coli; however, curcumin down-expressed blaIMP. In a previous study by Shariati et al. [30], synthesized nano-curcumins exhibited significant (P < 0.001) downregulation of the transcription of some virulence genes in PAO1 (16-fold) and MDR (13-fold) strains of P. aeruginosa, respectively. Another study by Kumbar et al. [31], showed that curcumin diminished the virulence of Porphyromonas gingivalis by reducing the expression of virulence factors genes. Also, Shen et al. [32], showed that silibinin, a flavonoid that is isolated from S. marianum, reduced the virulence of Streptococcus suis serotype 2. The decrease in the expression of virulence genes may be related to the effect of the tested compounds on QS genes, which play an important role in regulating other bacterial factors such as pathogenicity, biofilm production, and secretion systems [33]. In conclusion, this study showed the synergistic effects of curcumin and silybin against some of virulence factors and carbapenemase genes in MDR K. oxytoca. The results of this study provided a suitable platform for further investigations, especially in vivo experiments to verify these promising effects.


Major limitations of this study included lack of in vivo experiment, low number of samples and no investigation of curcumin and silybin effects on virulence gene expression of other nosocomial pathogens.

Availability of data and materials

The data of the current study are available from the corresponding author on reasonable request.





Minimum bactericidal concentration




Minimum inhibitory concentration


Mueller Hinton broth


  1. Yazdansetad S, Alkhudhairy MK, Najafpour R, Farajtabrizi E, Al-Mosawi RM, Saki M, et al. Preliminary survey of extended-spectrum β-lactamases (ESBLs) in nosocomial uropathogen Klebsiella pneumoniae in north-central Iran. Heliyon. 2019;5: e02349.

    Article  Google Scholar 

  2. Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections caused by carbapenem-resistant Enterobacteriaceae: an update on therapeutic options. Front Microbiol. 2019;10:80.

    Article  Google Scholar 

  3. Abbas AF, Al-Saadi AG, Alkhudhairy MK. Biofilm formation and virulence determinants of Klebsiella oxytoca clinical isolates from patients with colorectal cancer. J Gastrointest Cancer. 2020;51:855–60.

    Article  CAS  Google Scholar 

  4. Behzadi P, García-Perdomo HA, Karpiński TM, Issakhanian L. Metallo-ß-lactamases: a review. Mol Biol Rep. 2020;47:6281–94.

    Article  CAS  Google Scholar 

  5. Ghasemian A, Mobarez AM, Peerayeh SN, Abadi ATB, Khodaparast S, Nojoomi F. Report of plasmid-mediated colistin resistance in Klebsiella oxytoca from Iran. Rev Med Microbiol. 2018;29:59–63.

    Article  Google Scholar 

  6. Tsilipounidaki K, Athanasakopoulou Z, Müller E, Burgold-Voigt S, Florou Z, Braun SD, et al. Plethora of resistance genes in carbapenem-resistant gram-negative bacteria in Greece: no end to a continuous genetic evolution. Microorganisms. 2022;10:159.

    Article  CAS  Google Scholar 

  7. Gómez M, Valverde A, Del Campo R, Rodríguez JM, Maldonado-Barragán A. Phenotypic and molecular characterization of commensal, community-acquired and nosocomial Klebsiella spp. Microorganisms. 2021;9:2344.

    Article  Google Scholar 

  8. Alkhudhairy MK, Alshadeedi SM, Mahmood SS, Al-Bustan SA, Ghasemian A. Comparison of adhesin genes expression among Klebsiella oxytoca ESBL-non-producers in planktonic and biofilm mode of growth, and imipenem sublethal exposure. Microb Pathog. 2019;134: 103558.

    Article  CAS  Google Scholar 

  9. Behzadi P. Classical chaperone-usher (CU) adhesive fimbriome: uropathogenic Escherichia coli (UPEC) and urinary tract infections (UTIs). Folia Microbiol. 2020;65:45–65.

    Article  CAS  Google Scholar 

  10. Khonsari MS, Behzadi P, Foroohi F. The prevalence of type 3 fimbriae in Uropathogenic Escherichia coli isolated from clinical urine samples. Meta Gene. 2021;28: 100881.

    Article  CAS  Google Scholar 

  11. Lehti TA, Bauchart P, Heikkinen J, Hacker J, Korhonen TK, Dobrindt U, et al. Mat fimbriae promote biofilm formation by meningitis-associated Escherichia coli. Microbiology. 2010;156:2408–17.

    Article  CAS  Google Scholar 

  12. Ligthart K, Belzer C, De Vos WM, Tytgat HL. Bridging bacteria and the gut: functional aspects of type IV pili. Trends Microbiol. 2020;28:340–8.

    Article  CAS  Google Scholar 

  13. Bessam F, Mehdadi Z. Evaluation of the antibacterial and antifongigal activity of different extract of Flavonoïques Silybum marianum L. Adv Environ Biol. 2014;8:1–9.

    Google Scholar 

  14. Rahaman M, Rakib A, Mitra S, Tareq AM, Emran TB, Shahid-Ud-daula AF, et al. The genus curcuma and inflammation: overview of the pharmacological perspectives. Plants. 2021;10:63.

    Article  CAS  Google Scholar 

  15. Adamczak A, Ożarowski M, Karpiński TM. Curcumin, a natural antimicrobial agent with strain-specific activity. Pharmaceuticals (Basel). 2020;13:153.

    Article  CAS  Google Scholar 

  16. Krausz AE, Adler BL, Cabral V, Navati M, Doerner J, Charafeddine RA, et al. Curcumin encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine. 2015;11:195–206.

    Article  CAS  Google Scholar 

  17. Kong WY, Ngai SC, Goh BH, Lee LH, Htar TT, Chuah LH. Is curcumin the answer to future chemotherapy cocktail? Molecules. 2021;26:4329.

    Article  CAS  Google Scholar 

  18. Behzadi P, Gajdács M. Writing a strong scientific paper in medicine and the biomedical sciences: a checklist and recommendations for early career researchers. Biol Futur. 2021;72:395–407.

    Article  Google Scholar 

  19. Collee JG, Miles RS, Watt B. Tests for the Identification of Bacteria. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and MaCcartney Practical Microbiology. 4th ed. Livingstone: Churchill; 1996. p. 131–49.

    Google Scholar 

  20. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. 27th ed. CLSI supplement M100.Wayne, PA. 2017.

  21. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81.

    Article  CAS  Google Scholar 

  22. Urošević M, Nikolić L, Gajić I, Nikolić V, Dinić A, Miljković V. Curcumin: biological activities and modern pharmaceutical forms. Antibiotics (Basel). 2022;11:135.

    Article  Google Scholar 

  23. Bijak M. Silybin a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)—chemistry, bioavailability, and metabolism. Molecules. 2017;22:1942.

    Article  Google Scholar 

  24. Saki M, Seyed-Mohammadi S, Montazeri EA, Siahpoosh A, Moosavian M, Latifi SM. In vitro antibacterial properties of Cinnamomum zeylanicum essential oil against clinical extensively drug-resistant bacteria. Eur J Integr Med. 2020;37: 101146.

    Article  Google Scholar 

  25. Kamali E, Jamali A, Izanloo A, Ardebili A. In vitro activities of cellulase and ceftazidime, alone and in combination against Pseudomonas aeruginosa biofilms. BMC Microbiol. 2021;21:347.

    Article  CAS  Google Scholar 

  26. Khalil OA, Enbaawy MI, Taher Salah HM, Ragab E. In vitro investigation of the antibacterial effect of silver nanoparticles on ESBL-producing E. coli and Klebsiella spp. isolated from Pet animals. World Vet J. 2020;10:514–24.

    Article  Google Scholar 

  27. Evren E, Yurtcu E. In vitro effects on biofilm viability and antibacterial and antiadherent activities of silymarin. Folia Microbiol. 2015;60:351–6.

    Article  CAS  Google Scholar 

  28. Eslami M, Ghasemian A, Najafiolya Z, Mirforughi SA, Nojoomi F. Silymarin and curcumin effects on virulence and carbapenemase genes among multidrug-resistant Escherichia coli clinical isolates. Rev Med Microbiol. 2018;29:177–81.

    Article  Google Scholar 

  29. Zheng D, Huang C, Huang H, Zhao Y, Khan MR, Zhao H, et al. Antibacterial mechanism of curcumin: a review. Chem Biodivers. 2020;17: e2000171.

    Article  CAS  Google Scholar 

  30. Shariati A, Asadian E, Fallah F, Azimi T, Hashemi A, Yasbolaghi Sharahi J, et al. Evaluation of nano-curcumin effects on expression levels of virulence genes and biofilm production of multidrug-resistant Pseudomonas aeruginosa isolated from burn wound infection in Tehran. Iran Infect Drug Resist. 2019;12:2223–35.

    Article  CAS  Google Scholar 

  31. Kumbar VM, Peram MR, Kugaji MS, Shah T, Patil SP, Muddapur UM, et al. Effect of curcumin on growth, biofilm formation and virulence factor gene expression of Porphyromonas gingivalis. Odontology. 2021;109:18–28.

    Article  CAS  Google Scholar 

  32. Shen X, Liu H, Li G, Deng X, Wang J. Silibinin attenuates Streptococcus suis serotype 2 virulence by targeting suilysin. J App Microbiol. 2019;126:435–42.

    Article  CAS  Google Scholar 

  33. Tanhay Mangoudehi H, Zamani H, Shahangian SS, Mirzanejad L. Effect of curcumin on the expression of ahyI/R quorum sensing genes and some associated phenotypes in pathogenic Aeromonas hydrophila fish isolates. World J Microbiol Biotechnol. 2020;36:70.

    Article  CAS  Google Scholar 

Download references





Author information

Authors and Affiliations



FHO and NSKA: conceptualisation, data curation, formal analysis, investigation, methodology, project administration, writing—original draft preparation, writing—review and editing. FTA: data curation, formal analysis, writing-original draft preparation, writing—review and editing. HOMA: investigation, methodology, writing—review and editing. MM: investigation, methodology, writing—review and editing. MS: investigation, writing-original draft preparation, writing—review and editing. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hussein O. M. Al-Dahmoshi or Morteza Saki.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the University of Mosul, Mosul, Iraq according to the Declaration of Helsinki. No human and animal data or sample were included in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1

: Figure S1. Flow chart of the employed procedures in the present study.

Additional file 2

: Figure S2. Antibiotic resistance patterns of Klebsiella oxytoca isolates.

Additional file 3

: Figure S3. Microtiter plate assay showing moderate level of biofilm formation in different Klebsiella oxytoca isolates.

Additional file 4

: Figure S4. The expression of virulence and antibiotic resistance genes in exposure to 100 mg/mL of combined silybin and curcumin; "c" stands for control group without exposure neither to curcumin nor the silybin, "t" stand for treatment and "df" stand for decrease in fold value.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Omer, F.H., Al-Khafaji, N.S.K., Al-Alaq, F.T. et al. Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca. BMC Res Notes 15, 330 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Silybin
  • Curcumin
  • Antimicrobial effects
  • Virulence genes
  • Klebsiella oxytoca