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. 2016 Nov 22;17(11):1947.
doi: 10.3390/ijms17111947.

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus

Muhammad Usman Amin  1   2 , Muhammad Khurram  3 , Taj Ali Khan  4 , Hani S Faidah  5 , Zia Ullah Shah  6 , Shafiq Ur Rahman  7 , Abdul Haseeb  8 , Muhammad Ilyas  9 , Naseem Ullah  10 , Sahibzada Muhammad Umar Khayam  11 , Marcello Iriti  12
Affiliations

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus

Muhammad Usman Amin et al. Int J Mol Sci. .

Abstract

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region.

Keywords: MRSA; antibiotic resistance; combination therapy; flavonoids; phytochemicals; synergism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Average zone of inhibition (mm ± standard deviation) of luteolin against MRSA (methicillin-resistant Staphylococcus aureus) ATCC 43300 strain and MRSA clinical isolates (n = 100).
Figure 2
Figure 2
Average zone of inhibition (mm ± standard deviation) of luteolin (L) in combination with antibiotics against * MRSA clinical isolates (n =100); † MRSA ATCC 43300 strain. AMO = amoxicillin; AMP = ampicillin; CEPH = cephradine; CET = ceftriaxone; IMP = imipenem; ME = methicillin; VAN = vancomycin; LEV = levolfloxacin; CIP = ciprofloxacin; ERY = erythromycin; S-T = sulfamethoxazole-trimethoprim; CEF = cefixime.
Figure 3
Figure 3
Average zone of inhibition (mm ± standard deviation) of luteolin + quercetin against MRSA (methicillin-resistant Staphylococcus aureus) ATCC 43300 strain and MRSA clinical isolates (n = 100).
Figure 4
Figure 4
Average zone of inhibition (mm ± standard deviation) of quercetin (Q) + luteolin (L) in combination with antibiotics against * MRSA (methicillin-resistant Staphylococcus aureus) clinical isolates (n = 100) and † MRSA ATCC 43300 strain. (p < 0.05 for IMP; p < 0.001 ME, CET, CEPH, AMP, AMO).
Figure 5
Figure 5
Exact minimum inhibitory concentrations (MIC, µg/mL) by incremental increase approach of luteolin in combination with antibiotics (µg/mL) against * MRSA clinical isolates (n = 100) and † MRSA ATCC 43300 strain; results are expressed as mean ± standard deviation. (p < 0.001).
Figure 6
Figure 6
Minimum inhibitory concentration (MIC, µg/mL) of antibiotics and combination between antibiotics and luteolin (L) or quercetin + luteolin (Q + L) against * MRSA clinical isolates (n = 100) and † MRSA ATCC 43300strain; results are expressed as mean ± standard deviation (p < 0.001). Results for Q alone have been previously reported [13].
Figure 7
Figure 7
Potassium (K+) loss (ppm) caused by Quercetin (Q), luteolin (L) and quercetin + luteolin (Q + L), against MRSA ATCC 43300 strain and MRSA clinical isolates; results are expressed as mean ± standard deviation (p < 0.001). Results for Q alone have been previously reported [13].
Figure 8
Figure 8
Potassium (K+) loss (ppm) caused by luteolin and luteolin + quercetin (L + Q) in combination with antibiotics against * MRSA (methicillin-resistant Staphylococcus aureus) clinical isolates (n = 100) and † MRSA ATCC 43300strain; results are expressed as mean ± standard deviation (p < 0.01 for all combinations apart from AMO).
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