Systemic antibiotics combined with SRP offer additional clinical improvements compared to SRP alone. Although there were no statistically significant differences, there was a trend that for initially moderate and deep pockets, metronidazole or metronidazole combined with amoxicillin, resulted in clinical improvements that were more pronounced over doxycycline or azithromycin. Additionally, there was a trend that the magnitude of the clinical benefit became smaller over time (1 year).

For the treatment of patients with aggressive periodontitis, systemic antibiotics combined with non-surgical periodontal therapy resulted in a significant additional effect compared to non-surgical therapy alone. There is a visible trend that showed metronidazole + amoxicillin is the most potent antibiotic combination.

Abstract:The ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotidebinding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C motif/ABC signature present in all ABC nucleotidebinding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an α-helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2 sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationmitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation. These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux. Running title: Linker region of human ABCG2Keywords: ABC transporter, breast cancer resistance protein/ABCG2, ATP hydrolysis, C motif/ABC signature, drug efflux coupling, specific sequence. Abbreviations: ABC, ATP-binding cassette; MDR, multidrug resistanceRevised Manuscript Click here to download Manuscript CMLS_C2_R1.docx 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Click here to view linked References AbstractThe ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotidebinding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted.Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains. Predictions of disorder and of secondary structures indicated that this C2-sequence was highly mobile and located between an -helix and a loop similarly to the C-motif. Point mutations of the two first residues of the C2-sequence fully abolished the transport-coupled ATPase activity, and led to the complete loss of cell resistance to mitoxantrone. The interaction with potent, selective and non-competitive, ABCG2 inhibitors was also significantly altered upon mutation.These results suggest an important mechanistic role for the C2-sequence of the ABCG2 linker region in ATP binding and/or hydrolysis coupled to drug efflux.

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