ArticleAntimicrobial agents and chemotherapy2005
Role of the AcrAB-TolC efflux pump in determining susceptibility of Haemophilus influenzae to the novel peptide deformylase inhibitor LBM415.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Identification of the lydiamycin biosynthetic gene cluster in a plant pathogen guides structural revision and identification of molecular target.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tolerance to Haemophilus influenzae infection in human epithelial cells: Insights from a primary cell-based model.PLoS pathogens · 2024Article
- Copper Efflux System Required in Murine Lung Infection by Haemophilus influenzae Composed of a Canonical ATPase Gene and Tandem Chaperone Gene Copies.Infection and immunity · 2023Article
- Imipenem heteroresistance but not tolerance inFrontiers in microbiology · 2023Article
- Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in β-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan.BMC research notes · 2018Article
- XCC2366, A Gene Encoding A Putative TetR Family Transcriptional Regulator, is Required for Acriflavin Resistance and Virulence of Xanthomonas campestris pv. campestris.Current microbiology · 2017Article
- Transcriptional Modulation of Penicillin-Binding Protein 1b, Outer Membrane Protein P2 and Efflux Pump (AcrAB-TolC) during Heat Stress Is Correlated to Enhanced Bactericidal Action of Imipenem on Non-typeableFrontiers in microbiology · 2017Article
- Frequency of Spontaneous Resistance to Peptide Deformylase Inhibitor GSK1322322 in Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2015Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
- Article
- Fmt bypass in Pseudomonas aeruginosa causes induction of MexXY efflux pump expression.Antimicrobial agents and chemotherapy · 2009Article
- Review
- Article
- Inhibition of chlamydial infection in the genital tract of female mice by topical application of a peptide deformylase inhibitor.Microbiological research · 2009Article
- Squalamine: an appropriate strategy against the emergence of multidrug resistant gram-negative bacteria?PloS one · 2008Article
- First characterization of heterogeneous resistance to imipenem in invasive nontypeable Haemophilus influenzae isolates.Antimicrobial agents and chemotherapy · 2007Article
- Drug forecast - the peptide deformylase inhibitors as antibacterial agents.Therapeutics and clinical risk management · 2007Article
- Reduced susceptibility of Haemophilus influenzae to the peptide deformylase inhibitor LBM415 can result from target protein overexpression due to amplified chromosomal def gene copy number.Antimicrobial agents and chemotherapy · 2007Article
- Peptide deformylase inhibitors as potent antimycobacterial agents.Antimicrobial agents and chemotherapy · 2006Article
- Activity of LBM415 compared to those of 11 other agents against Haemophilus species.Antimicrobial agents and chemotherapy · 2006Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Haemophilus influenzae isolates vary widely in their susceptibilities to the peptide deformylase inhibitor LBM415 (MIC range, 0.06 to 32 microg/ml); however, on average, they are less susceptible than gram-positive organisms, such as Staphylococcus aureus and Streptococcus pneumoniae. Insertional inactivation of the H. influenzae acrB or tolC gene in strain NB65044 (Rd strain KW20) increased susceptibility to LBM415, confirming a role for the AcrAB-TolC pump in determining resistance. Consistent with this, sequencing of a PCR fragment generated with primers flanking the acrRA region from an LBM415-hypersusceptible H. influenzae clinical isolate revealed a genetic deletion of acrA. Inactivation of acrB or tolC in several clinical isolates with atypically reduced susceptibility to LBM415 (MIC of 16 microg/ml or greater) significantly increased susceptibility, confirming that the pump is also a determinant of decreased susceptibility in these clinical isolates. Examination of acrR, encoding the putative repressor of pump gene expression, from several of these strains revealed mutations introducing frameshifts, stop codons, and amino acid changes relative to the published sequence, suggesting that loss of pump repression leads to decreased susceptibility. Supporting this, NB65044 acrR mutants selected by exposure to LBM415 at 8 microg/ml had susceptibilities to LBM415 and other pump substrates comparable to the least sensitive clinical isolates and showed increased expression of pump genes.
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