Abstract
Disruption of gene HI0894 or HI0895 in Haemophilus influenzae Rd, homologs of Escherichia coli acrAB multidrug efflux genes, caused hypersusceptibility to erythromycin, rifampin, novobiocin, and dyes such as ethidium bromide and crystal violet and increased accumulation of radioactive erythromycin, showing that these genes are expressed and contribute to the baseline level resistance of this organism through active drug efflux. The gene disruption did not produce detectable changes in susceptibility to several other antibiotics, possibly because rapid influx of small antibiotic molecules through the large H. influenzae porin channels counterbalances their efflux.
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- Benz R., Janko K., Boos W., Läuger P. Formation of large, ion-permeable membrane channels by the matrix protein (porin) of Escherichia coli. Biochim Biophys Acta. 1978 Aug 17;511(3):305–319. doi: 10.1016/0005-2736(78)90269-9. [DOI] [PubMed] [Google Scholar]
- Clairoux N., Picard M., Brochu A., Rousseau N., Gourde P., Beauchamp D., Parr T. R., Jr, Bergeron M. G., Malouin F. Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada. Antimicrob Agents Chemother. 1992 Jul;36(7):1504–1513. doi: 10.1128/aac.36.7.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coulton J. W., Mason P., Dorrance D. The permeability barrier of Haemophilus influenzae type b against beta-lactam antibiotics. J Antimicrob Chemother. 1983 Nov;12(5):435–449. doi: 10.1093/jac/12.5.435. [DOI] [PubMed] [Google Scholar]
- Elhai J., Wolk C. P. A versatile class of positive-selection vectors based on the nonviability of palindrome-containing plasmids that allows cloning into long polylinkers. Gene. 1988 Aug 15;68(1):119–138. doi: 10.1016/0378-1119(88)90605-1. [DOI] [PubMed] [Google Scholar]
- Fleischmann R. D., Adams M. D., White O., Clayton R. A., Kirkness E. F., Kerlavage A. R., Bult C. J., Tomb J. F., Dougherty B. A., Merrick J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496–512. doi: 10.1126/science.7542800. [DOI] [PubMed] [Google Scholar]
- Hagman K. E., Pan W., Spratt B. G., Balthazar J. T., Judd R. C., Shafer W. M. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system. Microbiology. 1995 Mar;141(Pt 3):611–622. doi: 10.1099/13500872-141-3-611. [DOI] [PubMed] [Google Scholar]
- Herriott R. M., Meyer E. M., Vogt M. Defined nongrowth media for stage II development of competence in Haemophilus influenzae. J Bacteriol. 1970 Feb;101(2):517–524. doi: 10.1128/jb.101.2.517-524.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Köhler T., Michéa-Hamzehpour M., Henze U., Gotoh N., Curty L. K., Pechère J. C. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol. 1997 Jan;23(2):345–354. doi: 10.1046/j.1365-2958.1997.2281594.x. [DOI] [PubMed] [Google Scholar]
- Levy S. B. Active efflux mechanisms for antimicrobial resistance. Antimicrob Agents Chemother. 1992 Apr;36(4):695–703. doi: 10.1128/aac.36.4.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis K. Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem Sci. 1994 Mar;19(3):119–123. doi: 10.1016/0968-0004(94)90204-6. [DOI] [PubMed] [Google Scholar]
- Li X. Z., Livermore D. M., Nikaido H. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. Antimicrob Agents Chemother. 1994 Aug;38(8):1732–1741. doi: 10.1128/aac.38.8.1732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li X. Z., Nikaido H., Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948–1953. doi: 10.1128/aac.39.9.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lomovskaya O., Lewis K. Emr, an Escherichia coli locus for multidrug resistance. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8938–8942. doi: 10.1073/pnas.89.19.8938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ma D., Cook D. N., Alberti M., Pon N. G., Nikaido H., Hearst J. E. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol. 1995 Apr;16(1):45–55. doi: 10.1111/j.1365-2958.1995.tb02390.x. [DOI] [PubMed] [Google Scholar]
- Ma D., Cook D. N., Hearst J. E., Nikaido H. Efflux pumps and drug resistance in gram-negative bacteria. Trends Microbiol. 1994 Dec;2(12):489–493. doi: 10.1016/0966-842x(94)90654-8. [DOI] [PubMed] [Google Scholar]
- Nakae T. Identification of the outer membrane protein of E. coli that produces transmembrane channels in reconstituted vesicle membranes. Biochem Biophys Res Commun. 1976 Aug 9;71(3):877–884. doi: 10.1016/0006-291x(76)90913-x. [DOI] [PubMed] [Google Scholar]
- Nikaido H. Multidrug efflux pumps of gram-negative bacteria. J Bacteriol. 1996 Oct;178(20):5853–5859. doi: 10.1128/jb.178.20.5853-5859.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikaido H. Porins and specific channels of bacterial outer membranes. Mol Microbiol. 1992 Feb;6(4):435–442. doi: 10.1111/j.1365-2958.1992.tb01487.x. [DOI] [PubMed] [Google Scholar]
- Okusu H., Ma D., Nikaido H. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol. 1996 Jan;178(1):306–308. doi: 10.1128/jb.178.1.306-308.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saier M. H., Jr, Tam R., Reizer A., Reizer J. Two novel families of bacterial membrane proteins concerned with nodulation, cell division and transport. Mol Microbiol. 1994 Mar;11(5):841–847. doi: 10.1111/j.1365-2958.1994.tb00362.x. [DOI] [PubMed] [Google Scholar]
- Stuy J. H. Plasmid transfer in Haemophilus influenzae. J Bacteriol. 1979 Aug;139(2):520–529. doi: 10.1128/jb.139.2.520-529.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sánchez L., Puig M., Fusté C., Lorén J. G., Viñas M. Outer membrane permeability of non-typable Haemophilus influenzae. J Antimicrob Chemother. 1996 Feb;37(2):341–344. doi: 10.1093/jac/37.2.341. [DOI] [PubMed] [Google Scholar]
- Vachon V., Laprade R., Coulton J. W. Properties of the porin of Haemophilus influenzae type b in planar lipid bilayer membranes. Biochim Biophys Acta. 1986 Sep 25;861(1):74–82. doi: 10.1016/0005-2736(86)90373-1. [DOI] [PubMed] [Google Scholar]
- Vachon V., Lyew D. J., Coulton J. W. Transmembrane permeability channels across the outer membrane of Haemophilus influenzae type b. J Bacteriol. 1985 Jun;162(3):918–924. doi: 10.1128/jb.162.3.918-924.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young J. D., Blake M., Mauro A., Cohn Z. A. Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3831–3835. doi: 10.1073/pnas.80.12.3831. [DOI] [PMC free article] [PubMed] [Google Scholar]