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Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on Streptococcus pyogenes.

Siriwong S, Thumanu K, Hengpratom T, Eumkeb G - Evid Based Complement Alternat Med (2015)

Bottom Line: A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count.These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells.So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacology, Institute of Science, Suranaree University of Technology, 111 University Avenue, Suranaree Subdistrict, Muang District, Nakhon Ratchasima 30000, Thailand.

ABSTRACT
Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL(-1), respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.

No MeSH data available.


Related in: MedlinePlus

Ultrathin sections of log phase S. pyogenes DMST 30653 grown in CAMHB-LHB containing (a) control (drug-free); (b) ceftazidime (0.25 μg mL−1); (c) luteolin (64 μg mL−1); (d) quercetin (64 μg mL−1); (e) ceftazidime (0.09 μg mL−1) plus luteolin (12 μg mL−1); (f) ceftazidime (0.09 μg mL−1) plus quercetin (3 μg mL−1). ((a) 195,000x, bar 500 nm; (b) 7,000x, bar 1 μm; (c) 9,900x, bar 500 nm; (d) 15,000x, bar 500 nm; (e) 7,000x, bar 1 μm; (f) 9,900x, bar 500 nm; inset: (a) 34,000x, bar 200 nm; (b) 17,000x, bar 500 nm; (c) 29,000x, bar 200 nm; (d) 15,000x, bar 500 nm; (e) 15,000x, bar 500 nm; (f) 29,000x, bar 200 nm).
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fig5: Ultrathin sections of log phase S. pyogenes DMST 30653 grown in CAMHB-LHB containing (a) control (drug-free); (b) ceftazidime (0.25 μg mL−1); (c) luteolin (64 μg mL−1); (d) quercetin (64 μg mL−1); (e) ceftazidime (0.09 μg mL−1) plus luteolin (12 μg mL−1); (f) ceftazidime (0.09 μg mL−1) plus quercetin (3 μg mL−1). ((a) 195,000x, bar 500 nm; (b) 7,000x, bar 1 μm; (c) 9,900x, bar 500 nm; (d) 15,000x, bar 500 nm; (e) 7,000x, bar 1 μm; (f) 9,900x, bar 500 nm; inset: (a) 34,000x, bar 200 nm; (b) 17,000x, bar 500 nm; (c) 29,000x, bar 200 nm; (d) 15,000x, bar 500 nm; (e) 15,000x, bar 500 nm; (f) 29,000x, bar 200 nm).

Mentions: Electron micrographs of log phase of S. pyogenes cells in the presence of luteolin, quercetin, and ceftazidime alone and ceftazidime plus luteolin or quercetin are presented in Figure 5. The peptidoglycan and cytoplasmic membrane can be distinguished from the control group. The morphology of the cells had normal appearance (Figure 5(a)). The S. pyogenes cells treated with ceftazidime alone are revealed in Figure 5(b). The cell division of a lot of these cells may be interrupted and delayed result in cell shape distortions. The average cross-sectional cell areas of these cells were larger than the control, but not significantly (P > 0.01) (Figure 6). The luteolin treated alone displayed a little repaired cytoplasmic membrane, and cell shape distortion or broken cells in a lot of these cells compared to the control (Figure 5(c)). The quercetin treated cells alone are presented in Figure 5(d). These treated cells revealed thinner or disappearing peptidoglycan, cytoplasmic membrane damage, cell shape distortion, and broken cells in many of these cells compared with controls. The average cell areas of these flavonoids treated alone were a bit larger than the control, despite not significantly different (P > 0.01). Furthermore, the micrograph of these cells after exposure to ceftazidime plus luteolin is shown in Figure 5(e). The result exhibited that the cell division of many of these cells may be interrupted leading to twisted and irregular cell shape. Some of these cells revealed peptidoglycan and cytoplasmic membrane damage. Obviously, the average cell areas of these cells were significantly larger than controls (P < 0.01) (Figure 6). Likewise, Figure 5(f) reveals the ceftazidime plus quercetin treated cells. The cell division process in most of these cells may also be interrupted resulting in deformed and eccentric cell shape. The peptidoglycan and the cytoplasmic membrane in most of these cells were damaged. These average cell areas were larger than the control, but not significantly (P > 0.01) (Figure 6).


Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on Streptococcus pyogenes.

Siriwong S, Thumanu K, Hengpratom T, Eumkeb G - Evid Based Complement Alternat Med (2015)

Ultrathin sections of log phase S. pyogenes DMST 30653 grown in CAMHB-LHB containing (a) control (drug-free); (b) ceftazidime (0.25 μg mL−1); (c) luteolin (64 μg mL−1); (d) quercetin (64 μg mL−1); (e) ceftazidime (0.09 μg mL−1) plus luteolin (12 μg mL−1); (f) ceftazidime (0.09 μg mL−1) plus quercetin (3 μg mL−1). ((a) 195,000x, bar 500 nm; (b) 7,000x, bar 1 μm; (c) 9,900x, bar 500 nm; (d) 15,000x, bar 500 nm; (e) 7,000x, bar 1 μm; (f) 9,900x, bar 500 nm; inset: (a) 34,000x, bar 200 nm; (b) 17,000x, bar 500 nm; (c) 29,000x, bar 200 nm; (d) 15,000x, bar 500 nm; (e) 15,000x, bar 500 nm; (f) 29,000x, bar 200 nm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Ultrathin sections of log phase S. pyogenes DMST 30653 grown in CAMHB-LHB containing (a) control (drug-free); (b) ceftazidime (0.25 μg mL−1); (c) luteolin (64 μg mL−1); (d) quercetin (64 μg mL−1); (e) ceftazidime (0.09 μg mL−1) plus luteolin (12 μg mL−1); (f) ceftazidime (0.09 μg mL−1) plus quercetin (3 μg mL−1). ((a) 195,000x, bar 500 nm; (b) 7,000x, bar 1 μm; (c) 9,900x, bar 500 nm; (d) 15,000x, bar 500 nm; (e) 7,000x, bar 1 μm; (f) 9,900x, bar 500 nm; inset: (a) 34,000x, bar 200 nm; (b) 17,000x, bar 500 nm; (c) 29,000x, bar 200 nm; (d) 15,000x, bar 500 nm; (e) 15,000x, bar 500 nm; (f) 29,000x, bar 200 nm).
Mentions: Electron micrographs of log phase of S. pyogenes cells in the presence of luteolin, quercetin, and ceftazidime alone and ceftazidime plus luteolin or quercetin are presented in Figure 5. The peptidoglycan and cytoplasmic membrane can be distinguished from the control group. The morphology of the cells had normal appearance (Figure 5(a)). The S. pyogenes cells treated with ceftazidime alone are revealed in Figure 5(b). The cell division of a lot of these cells may be interrupted and delayed result in cell shape distortions. The average cross-sectional cell areas of these cells were larger than the control, but not significantly (P > 0.01) (Figure 6). The luteolin treated alone displayed a little repaired cytoplasmic membrane, and cell shape distortion or broken cells in a lot of these cells compared to the control (Figure 5(c)). The quercetin treated cells alone are presented in Figure 5(d). These treated cells revealed thinner or disappearing peptidoglycan, cytoplasmic membrane damage, cell shape distortion, and broken cells in many of these cells compared with controls. The average cell areas of these flavonoids treated alone were a bit larger than the control, despite not significantly different (P > 0.01). Furthermore, the micrograph of these cells after exposure to ceftazidime plus luteolin is shown in Figure 5(e). The result exhibited that the cell division of many of these cells may be interrupted leading to twisted and irregular cell shape. Some of these cells revealed peptidoglycan and cytoplasmic membrane damage. Obviously, the average cell areas of these cells were significantly larger than controls (P < 0.01) (Figure 6). Likewise, Figure 5(f) reveals the ceftazidime plus quercetin treated cells. The cell division process in most of these cells may also be interrupted resulting in deformed and eccentric cell shape. The peptidoglycan and the cytoplasmic membrane in most of these cells were damaged. These average cell areas were larger than the control, but not significantly (P > 0.01) (Figure 6).

Bottom Line: A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count.These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells.So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacology, Institute of Science, Suranaree University of Technology, 111 University Avenue, Suranaree Subdistrict, Muang District, Nakhon Ratchasima 30000, Thailand.

ABSTRACT
Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL(-1), respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.

No MeSH data available.


Related in: MedlinePlus