Amino Acid Substitution in the Major Multidrug Efflux Transporter Protein AcrB Contributes to Low Susceptibility to Azithromycin in Haemophilus influenzae | Antimicrobial Agents and Chemotherapy

DOI: 10.1128/AAC.01337-17

Article Figures & Data

Tables

Additional Files

TABLE 1

Characteristics and MICs of bacterial strains used in this study

Strain	Serotype	ST	Deletion site in acrR	MIC (μg/ml)^a
				CLR	CLR + CCCP		AZM	AZM + CCCP		EB
				CLR	0.75 μg/ml CCCP	1.5 μg/ml CCCP	AZM	0.75 μg/ml CCCP	1.5 μg/ml CCCP	EB
2012-42	NT^b	156	Nucleotide 141^c	32	16	4	8	4	1	≥16
2011-70	NT	156	Nucleotide 141^c	32	16	1	4	1	0.25	8
Rd	NT	47	None^c	8	4	0.25	1	0.5	≤0.06	1
Rd_42acr	NT	47	Nucleotide 141^c	32	16	2	8	4	0.5	8
Rd_70acr	NT	47	Nucleotide 141	32	16	1	4	2	0.13	4

↵a CLR, clarithromycin; AZM, azithromycin; EB, ethidium bromide; CCCP, carbonyl cyanide m-chlorophenylhydrazone.
↵b NT, nontypeable.
↵c Results of a previous study by Seyama et al. (5).

TABLE 2
Detailed MICs of H. influenzae strain Rd and strains with acr mutations
Strain Relative acrB mRNA level^a MIC (μg/ml) Ratio^b
CLR AZM CLR AZM
Rd 0.82 ± 0.24 8 1 1 1
Rd_42acr 1.86 ± 0.35^c 30 8 3.8 8
Rd_70acr 1.45 ± 0.09^c 26 3.5 3.3 3.5
↵a The transcription levels were calculated in comparison with the gyrB transcription level. The measurements of acrB transcription levels were performed at least three times on independent occasions.
↵b Ratio of each MIC to that of H. influenzae Rd.
↵c P < 0.05, Rd versus Rd_42acr and Rd versus Rd_70acr.

Additional Files

Tables

Supplemental material

Supplemental file 1 -
Supplemental Figures S1 and S2

PDF, 150K

Print

KEYWORDS

Bacterial Proteins

Drug Resistance, Bacterial

Haemophilus influenzae

azithromycin low susceptibility

Related Articles

Cited By...