Journal: bioRxiv

Article Title: Identification, Characterization and Mode of Action of Corynaridin, a Novel Linaridin from Corynebacterium lactis

doi: 10.1101/2022.05.11.491181

Figure Lengend Snippet: RPC fraction was used undiluted and in a dilution series against (a) C. glutamicum ATCC 13032, (b) C. striatum DSM 20668 and (c) C. amycolatum DSM 6922. For each spot, 10 μL sample were used. A nisin standard (250 μg/mL) and HPLC-grade H 2 O (control) were used as positive and negative controls, respectively.

Article Snippet: Notably, besides non-pathogenic, environmental and commensal bacteria including C. glutamicum ATCC 13032 , also emerging multi-resistant pathogens like C. striatum DSM 20668 ( ) and C. amycolatum DSM 6922 ( ) were inhibited by RPC-purified corynaridin.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Genotypes and phenotypes of P. acnes NAI003 r mutants

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques: Mutagenesis

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Synthetic route to NAI003. DPPA, diphenyl phosphorazidate.

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: MICs of GE2270A, compound 2, and NAI003 against selected Gram-positive bacteria

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: MICs of GE2270A, compound 2, and NAI003 against P. acnes

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Killing kinetics of P. acnes. Effect of NAI003 (closed symbols, solid lines) and clindamycin (empty symbols, dashed lines) on the viability of P. acnes, using the clindamycin-sensitive ND062711 (A) and clindamycin-resistant ND06311 (B) isolates. Compounds were added at 1× MIC (triangles), 10× MIC (circles), or 100× MIC (squares). In panel B, clindamycin was used at only 1× (open triangles) and 4× (open diamonds) the MIC. Growth controls are shown for both panels by a thick dashed line.

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Effects of GE2270A and NAI003 on the electrophoretic mobility of EF-Tu and on in vitro translation. (A) Migration on native polyacrylamide gel of E. coli EF-Tu (preincubated with GTP) in the presence of increasing concentrations (from left to right, 0.1, 0.5, 1, 5, 10, 50, and 100 μM) of GE2270A (lanes 2 to 8) or NAI003 (lanes 9 to 15). (B) Electrophoretic mobility difference between EF-Tu–GTP alone (lane 1) and in the presence of 1 μM GE2270A (lane 2) or of 10 μM NAI003 (lane 3). The two arrows indicate the different migrations of EF-Tu in complex with GE2270A or with NAI003. (C) Inhibition by GE2270A (●) or NAI003 (■) in a protein synthesis system based on an E. coli extract programmed with 027-IF2Cp(A) mRNA.

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques: In Vitro, Migration, Inhibition

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Effect of GE2270A and NAI003 on the electrophoretic mobilities of different EF-Tus. Migration on native polyacrylamide gels of EF-Tu from E. coli (A), S. aureus (B), P. acnes (C), and S. pyogenes (D) in the presence of increasing concentrations (1, 4, 19, 50, and 100 μM, respectively) of GE2270A (lanes 2 to 6) or of NAI003 (lanes 7 to 11).

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques: Migration

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Effects of GE2270A and NAI003 on in vitro protein synthesis. (A) Poly(U)-dependent incorporation of [3H]Phe in a hot-trichloroacetic acid-insoluble product in the presence of increasing concentrations of different EF-Tus. The amounts of Phe incorporated with E. coli EF-Tu are indicated on the right ordinate, while those obtained with EF-Tu from P. acnes, S. aureus, E. faecalis, or S. pyogenes are indicated on the left ordinate. (B and C) Effects of GE2270A (B) and NAI003 (C) on in vitro translation with different EF-Tus. Symbols for EF-Tu are as follows: black circles, E. coli; red diamonds, P. acnes; purple squares, E. faecalis; green inverted triangles, S. aureus; turquoise triangles, S. pyogenes.

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques: In Vitro

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Genotypes and phenotypes of P. acnes NAI003 r mutants

Article Snippet: When transposed to the crystal structure of T. thermophilus EF-Tu, the other observed mutations ( ) map to domain I (H68Q and V81A) or II (M263T), although they do not appear to be directly involved in antibiotic binding. table ft1 table-wrap mode="anchored" t5 TABLE 4 caption a7 Strain tuf mutation a EF-Tu MIC (μg/ml) of antibiotic: Substitution b Domain c NAI003 GE2270A Compound 2 ATCC 6922 0.015 0.007 ≤0.06 L1015R13 C207A H68Q I 8 0.015 0.5 L1015R51 T245C V81A I 32 ≤0.06 1 L1015R6 G300T Q99H I 8 0.015 1 L1015R5 G300T Q99H I 2 0.007 0.5 L1015R7 G300T Q99H I 1 0.003 0.25 L1015R24 G781C G260R II >128 0.125 0.25 L1015R8 G781T G260C II 32 0.125 2 L1015R96 T791C M263T II 4 ≤0.06 4 L1015R73 A830G N276S II 1 0.007 0.125 L1015R72 A830G N276S II 2 0.007 0.25 L1015R21 C831G N276K II 1 0.03 0.25 L1015R86 None None 128 0.25 4 Open in a separate window a Nucleotide numbering is based on tuf sequence from P. acnes KPA171202 ( 15 ). b Amino acid numbering is based on EF-Tu sequence from P. acnes KPA171202 ( 15 ). c As defined by Parmeggiani et al. ( 11 ).

Techniques: Mutagenesis

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: MICs of GE2270A, compound 2, and NAI003 against P. acnes

Article Snippet: The occurrence of spontaneous resistant mutants of P. acnes ATCC 6922 was determined by plating 0.1 ml of a stationary-phase culture on WCA containing NAI003 or GE2270A at 1 or 10 μg/ml.

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes

doi: 10.1128/AAC.05155-14

Figure Lengend Snippet: Genotypes and phenotypes of P. acnes NAI003 r mutants

Article Snippet: The occurrence of spontaneous resistant mutants of P. acnes ATCC 6922 was determined by plating 0.1 ml of a stationary-phase culture on WCA containing NAI003 or GE2270A at 1 or 10 μg/ml.

Techniques: Mutagenesis