# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 6186 | 0 | 1.0000 | A triclosan-ciprofloxacin cross-resistant mutant strain of Staphylococcus aureus displays an alteration in the expression of several cell membrane structural and functional genes. Triclosan is an antimicrobial agent found in many consumer products. Triclosan inhibits the bacterial fatty acid biosynthetic enzyme, enoyl-ACP reductase (FabI). Decreased susceptibility to triclosan correlates with ciprofloxacin resistance in several bacteria. In these bacteria, resistance to both drugs maps to genes encoding multi-drug efflux pumps. The focus of this study was to determine whether triclosan resistance contributes to ciprofloxacin resistance in Staphylococcus aureus. In S. aureus, triclosan resistance maps to a fabI homolog and ciprofloxacin resistance maps to genes encoding DNA gyrase, topoisomerase IV and to the multi-drug efflux pump, NorA. Using a norA overexpressing mutant, we demonstrated that upregulation of NorA does not lead to triclosan resistance. To further investigate triclosan/ciprofloxacin resistance in S. aureus, we isolated triclosan/ciprofloxacin-resistant mutants. The mutants were screened for mutations in the genes encoding the targets of triclosan and ciprofloxacin. One mutant, JJ5, was wild-type for all sequences analyzed. We next monitored the efflux of triclosan from JJ5 and determined that triclosan resistance in the mutant was not due to active efflux of the drug. Finally, gene expression profiling demonstrated that an alteration in cell membrane structural and functional gene expression is likely responsible for triclosan and ciprofloxacin resistance in JJ5. | 2007 | 17997080 |
| 6188 | 1 | 0.9998 | Quinolone mode of action. Physical studies have further defined interactions of quinolones with their principal target, DNA gyrase. The binding of quinolones to the DNA gyrase-DNA complex suggests 2 possible binding sites of differing affinities. Mutations in either the gyrase A gene (gyrA) or the gyrase B gene (gyrB) that affect quinolone susceptibility also affect drug binding, with resistance mutations causing decreased binding and hypersusceptibility mutations causing increased binding. Combinations of mutations in both GyrA and GyrB have further demonstrated the contribution of both subunits to the quinolone sensitivity of intact bacteria and purified DNA gyrase. A working model postulates initial binding of quinolones to proximate sites on GyrA and GyrB. This initial binding then produces conformational changes that expose additional binding sites, possibly involving DNA. Quinolones also inhibit the activities of Escherichia coli topoisomerase IV (encoded by the parC and parE genes), but at concentrations higher than those inhibiting DNA gyrase. The patterns of resistance mutations in gryA and parC suggest that topoisomerase IV may be a secondary drug target in E. coli and Neisseria gonorrhoeae. In contrast, in Staphylococcus aureus these patterns suggest that topoisomerase IV may be a primary target of quinolone action. Regulation of expression of membrane efflux transporters may contribute to quinolone susceptibility in both Gram-positive and Gram-negative bacteria. The substrate profile of the NorA efflux transporter of S. aureus correlates with the extent to which the activity of quinolone substrates is affected by overexpression of NorA. In addition, the Emr transporter of E. coli affects susceptibility to nalidixic acid, and the MexAB OprK transport system of Pseudomonas aeruginosa affects susceptibility to ciprofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS) | 1995 | 8549276 |
| 6187 | 2 | 0.9997 | Mechanisms of fluoroquinolone resistance: an update 1994-1998. Fluoroquinolone resistance is mediated by target changes (DNA gyrase and/or topoisomerase IV) and/or decreased intracellular accumulation. The genes (gyrA/gyrB/parC/parE) and proteins of DNA topoisomerase IV show great similarity, both at the nucleotide and amino acid sequence level to those of DNA gyrase. It has been shown that there are hotspots, called the quinolone resistance determining region (QRDR), for mutations within gyrA and parC. Based on the Escherichia coli co-ordinates, the hotspots most favoured for giving rise to decreased susceptibility and/or full resistance to quinolones are at serine 83 and aspartate 87 of gyrA, and at serine 79 and aspartate 83 for parC. Few mutations in gyrB or parE/grlB of any bacteria have been described. Efflux of fluoroquinolones is the major cause of decreased accumulation of these agents; for Staphylococcus aureus, the efflux pump involved in norfloxacin resistance is NorA, and for Streptococcus pneumoniae, PmrA. By analysis of minimum inhibitory concentration (MIC) data derived in the presence and absence of the efflux inhibitor reserpine, it has been shown that up to 50% of ciprofloxacin-resistant clinical isolates of S. pneumoniae may possess enhanced efflux. This suggests that efflux may be an important mechanism of clinical resistance in this species. In Pseudomonas aeruginosa, several efflux operons have been demonstrated genetically and biochemically. These operons are encoded by mex (Multiple EffluX) genes: mexAmexB-oprM, mexCD-OprJ system and mexEF-oprN system. The E. coli efflux pump is the acrAB-tolC system. Both the mar operon and the sox operon can give rise to multiple antibiotic resistance. It has been shown that mutations giving rise to increased expression of the transcriptional activators marA and soxS affect the expression of a variety of different genes, including ompF and acrAB. The net result is that expression of OmpF is reduced and much less drug is able to enter the cell; expression of acrAB is increased, enhancing efflux from the cell. | 1999 | 10553699 |
| 6323 | 3 | 0.9997 | Reduced Susceptibility to Antiseptics Is Conferred by Heterologous Housekeeping Genes. Antimicrobial resistance is common in the microbial inhabitants of the human oral cavity. Antimicrobials are commonly encountered by oral microbes as they are present in our diet, both naturally and anthropogenically, and also used in oral healthcare products and amalgam fillings. We aimed to determine the presence of genes in the oral microbiome conferring reduced susceptibility to common antimicrobials. From an Escherichia coli library, 12,277 clones were screened and ten clones with reduced susceptibility to triclosan were identified. The genes responsible for this phenotype were identified as fabI, originating from a variety of different bacteria. The gene fabI encodes an enoyl-acyl carrier protein reductase (ENR), which is essential for fatty acid synthesis in bacteria. Triclosan binds to ENR, preventing fatty acid synthesis. By introducing the inserts containing fabI, ENR is likely overexpressed in E. coli, reducing the inhibitory effect of triclosan. Another clone was found to have reduced susceptibility to cetyltrimethylammonium bromide and cetylpyridinium chloride. This phenotype was conferred by a UDP-glucose 4-epimerase gene, galE, homologous to one from Veillonella parvula. The product of galE is involved in lipopolysaccharide production. Analysis of the E. coli host cell surface showed that the charge was more positive in the presence of galE, which likely reduces the binding of these positively charged antiseptics to the bacteria. This is the first time galE has been shown to confer resistance against quaternary ammonium compounds and represents a novel, epimerase-based, global cell adaptation, which confers resistance to cationic antimicrobials. | 2018 | 28604259 |
| 643 | 4 | 0.9996 | Effect of overexpression of small non-coding DsrA RNA on multidrug efflux in Escherichia coli. OBJECTIVES: Several putative and proven drug efflux pumps are present in Escherichia coli. Because many such efflux pumps have overlapping substrate spectra, it is intriguing that bacteria, with their economically organized genomes, harbour such large sets of multidrug efflux genes. To understand how bacteria utilize these multiple efflux pumps, it is important to elucidate the process of pump expression regulation. The aim of this study was to determine a regulator of the multidrug efflux pump in this organism. METHODS: We screened a genomic library of E. coli for genes that decreased drug susceptibility in this organism. The library was developed from the chromosomal DNA of the MG1655 strain, and then the recombinant plasmids were transformed into an acrB-deleted strain. Transformants were screened for resistance to various antibiotics including oxacillin. RESULTS: We found that the multidrug susceptibilities of the acrB-deleted strain were decreased by the overexpression of small non-coding DsrA RNA as well as by the overexpression of known regulators of multidrug efflux pumps. Plasmids carrying the dsrA gene conferred resistance to oxacillin, cloxacillin, erythromycin, rhodamine 6G and novobiocin. DsrA decreased the accumulation of ethidium bromide in E. coli cells. Furthermore, expression of mdtE was significantly increased by dsrA overexpression, and the decreased multidrug susceptibilities modulated by DsrA were dependent on the MdtEF efflux pump. CONCLUSIONS: These results indicate that DsrA modulates multidrug efflux through activation of genes encoding the MdtEF pump in E. coli. | 2011 | 21088020 |
| 6300 | 5 | 0.9996 | Assessing the role of the RND efflux pump in metronidazole resistance of Helicobacter pylori by RT-PCR assay. INTRODUCTION: Metronidazole is a significant antibiotic used for eradication of Helicobacter pylori infections and it is of notice that metronidazole-resistant clinical isolates have been found in high rates worldwide. While the RND family of efflux pumps plays a central role in drug resistance among Gram-negative bacteria, this is questionable for H. pylori. METHODOLOGY: To understand whether TolC homologues of RND pumps contribute to metronidazole resistance in H. pylori isolates, expression of four TolC homologous genes of five resistant clinical isolates exposed to varying concentrations of metronidazole were evaluated by RT-PCR and transcriptional analysis. RESULTS: The results indicate that excess amounts of metronidazole are able to increase the expression level of these genes at the transcriptional stage. CONCLUSIONS: Therefore, it may be hypothesized that use of metronidazole in H. pyori infection can induce metronidazole resistance. Furthermore, the RND family of efflux pumps may contribute to metronidazole resistance in clinical isolates of H. pylori. | 2011 | 21389587 |
| 6295 | 6 | 0.9996 | Anaerobiosis and Mutations Can Reduce Susceptibility of Pseudomonas aeruginosa to Tobramycin Without Reducing the Cellular Concentration of the Antibiotic. Chronic infections of Pseudomonas aeruginosa are commonly treated with tobramycin. During infections, the bacteria can exist under conditions of oxygen deprivation that render them less susceptible to this antibiotic. The aims of this research were to investigate the genetic basis of tobramycin resistance under anaerobic conditions, and to investigate the effects of anaerobiosis and mutations on the cellular concentration of tobramycin. Ten mutants with lowered susceptibility to tobramycin than wild-type bacteria were evolved from a laboratory reference strain under anaerobic conditions. Mutations were identified by genome sequencing. Mutations had arisen most frequently in the fusA1 gene that encodes elongation factor EF-G1A and in genes involved in twitching motility. Cellular concentrations of tobramycin were then measured. Mutations in fusA1 or absence of the MexXY efflux pump that is associated with tobramycin resistance did not alter the cellular tobramycin concentration under either anaerobic or aerobic conditions. Anaerobic growth reduced the cellular concentration of tobramycin, relative to aerobically grown bacteria, in some but not all of five tested P. aeruginosa isolates. Overall, our findings indicate that anaerobiosis and mutations that reduce aminoglycoside effectiveness do not lower the cellular concentration of antibiotic but instead reduce susceptibility through other mechanisms. | 2025 | 40005562 |
| 6324 | 7 | 0.9996 | Genetic and biochemical basis of tetracycline resistance. Properties of several, well characterized, tetracycline resistance determinants were compared. The determinants in Tn1721 and Tn10 (both from Gram-negative bacteria) each contain two genes; one encodes a repressor that regulates both its own transcription and that of a membrane protein that confers resistance by promoting efflux of the drug. Determinants from Gram-positive bacteria also encode efflux proteins, but expression of resistance is probably regulated by translational attenuation. The likely tetracycline binding site (a common dipeptide) in each efflux protein was predicted. The presence of the common binding site is consistent with the ability of an efflux protein originating in Bacillus species to be expressed in Escherichia coli. | 1986 | 3542941 |
| 8942 | 8 | 0.9996 | Indole-Induced Activities of β-Lactamase and Efflux Pump Confer Ampicillin Resistance in Pseudomonas putida KT2440. Indole, which is widespread in microbial communities, has received attention because of its effects on bacterial physiology. Pseudomonas putida and Pseudomonas aeruginosa can acquire ampicillin (Amp) resistance during growth on indole-Amp agar. Transcriptome, mutant, and inhibitor studies have suggested that Amp resistance induced by indole can be attributed to increased gene expression of ttgAB encoding two genes of RND-type multidrug efflux operons and an ampC encoding β-lactamase. Expression, enzyme activities, and mutational analyses indicated that AmpC β-lactamase is important for acquiring Amp resistance of P. putida in the presence of indole. Here, we show, for the first time, that volatile indole increased Amp-resistant cells. Consistent with results of the volatile indole assay, a low concentration of indole in liquid culture promoted growth initially, but led to mutagenesis after indole was depleted, which could not be observed at high indole concentrations. Interestingly, ttgAB and ampC gene expression levels correlate with the concentration of indole, which might explain the low number of Amp-mutated cells in high indole concentrations. The expression levels of genes involved in mutagenesis, namely rpoS, recA, and mutS, were also modulated by indole. Our data indicates that indole reduces Amp-induced heterogeneity by promoting expression of TtgABC or MexAB-OprM efflux pumps and the indole-induced β-lactamase in P. putida and P. aeruginosa. | 2017 | 28352264 |
| 6327 | 9 | 0.9996 | The Response of Enterococcus faecalis V583 to Chloramphenicol Treatment. Many Enterococcus faecalis strains display tolerance or resistance to many antibiotics, but genes that contribute to the resistance cannot be specified. The multiresistant E. faecalis V583, for which the complete genome sequence is available, survives and grows in media containing relatively high levels of chloramphenicol. No specific genes coding for chloramphenicol resistance has been recognized in V583. We used microarrays to identify genes and mechanisms behind the tolerance to chloramphenicol in V583, by comparison of cells treated with subinhibitory concentrations of chloramphenicol and untreated V583 cells. During a time course experiment, more than 600 genes were significantly differentially transcribed. Since chloramphenicol affects protein synthesis in bacteria, many genes involved in protein synthesis, for example, genes for ribosomal proteins, were induced. Genes involved in amino acid biosynthesis, for example, genes for tRNA synthetases and energy metabolism were downregulated, mainly. Among the upregulated genes were EF1732 and EF1733, which code for potential chloramphenicol transporters. Efflux of drug out of the cells may be one mechanism used by V583 to overcome the effect of chloramphenicol. | 2010 | 20628561 |
| 6260 | 10 | 0.9996 | Mechanisms of resistance to fluoroquinolones: state-of-the-art 1992-1994. This paper gives an update on the mechanisms of bacterial resistance to fluoroquinolones. The laboratory techniques currently used to determine the mechanism(s) of resistance are outlined, including the use of restriction fragment length polymorphism and single-stranded conformational polymorphism analysis of mutations in gyrA. Alterations in gyrA have continued to be the most reported cause of resistance, with high level resistance due to 2 or more mutations in this gene. Recently, mutations in gyrA of Mycobacterium tuberculosis and Campylobacter jejuni have been described. Complementation studies with plasmid encoded cloned gyrB from Escherichia coli suggest that high fluoroquinolone resistance (minimum inhibitory concentration = 32 mg/L) in Salmonella typhimurium can be due to mutation in both gyrA and gyrB. Decreased fluoroquinolone accumulation into E. coli has been shown to be due to mutations in a number of genes at different loci. Current interest has focused upon the marRAB and soxRS loci, with mutations in genes of either loci giving rise to decreased susceptibility to several unrelated drugs, including fluoroquinolones, tetracycline, chloramphenicol and some beta-lactams, and decreased expression of OmpF. The genetic characterisation of fluoroquinolone efflux from Staphylococcus aureus has shown that efflux occurs in both fluoroquinolone-susceptible and -resistant bacteria. The most likely cause of resistance is overexpression of NorA, giving rise to increased efflux. Recently, 2 efflux systems in Pseudomonas aeruginosa have been proposed, MexA-MexB-OprK and MexC-MexD-OprM, conferring decreased susceptibility to fluoroquinolones, tetracycline, chloramphenicol and some beta-lactams.(ABSTRACT TRUNCATED AT 250 WORDS) | 1995 | 8549336 |
| 8218 | 11 | 0.9996 | Mechanism of plasmic-mediated resistance to cadmium in Staphylococcus aureus. The mechanism of plasmid-mediated resistance to cadmium in Staphylococcus aureus was investigated. Protein synthesis in cell-free extracts from resistant or susceptible bacteria was equally susceptible to inhibition by Cd(2+), but spheroplasts from resistant bacteria retained their resistance. Resistant bacteria did not have a decreased affinity for cations in general, nor was active metabolism required for exclusion of Cd(2+). The kinetics of Cd(2+) uptake into susceptible and resistant bacteria suggested that the conformation of membrane proteins in resistant bacteria may be important in the exclusion of Cd(2+). | 1975 | 1137361 |
| 6326 | 12 | 0.9996 | Identification of novel metronidazole-inducible genes in Mycobacterium smegmatis using a customized amplification library. The incidence of antibiotic resistance in pathogenic bacteria is rising. Bacterial resistance may be a natural defense of organisms, or it may result from spontaneous mutations or the acquisition of exogenous resistance genes. We grew spontaneous metronidazole-resistant Mycobacterium smegmatis mutants on solid medium cultures and employed differential expression using a customized amplification library to analyze the global gene profiles of metronidazole-resistant mutants under hypoxic conditions. In total, 66 genes involved in metronidazole resistance were identified and functionally characterized using the gene role category of M. smegmatis. Overall, genes associated with cell wall synthesis, such as methyltransferase and glycosyltransferase, and genes encoding drug transporters were highly expressed. The genes may be involved in the natural drug resistance of mycobacteria by increasing mycobacterial cell wall permeability and the efflux pumps of active drugs. In addition, the genes may play a role in dormancy. The genes identified in this study may lead to a better understanding of the mechanisms of metronidazole resistance during dormancy. | 2008 | 18373646 |
| 6253 | 13 | 0.9996 | The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin. The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M. abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria. | 2019 | 31540480 |
| 6294 | 14 | 0.9996 | Comparison of Gene Expression Profiles of Uropathogenic Escherichia Coli CFT073 after Prolonged Exposure to Subinhibitory Concentrations of Different Biocides. Biocides are chemical compounds widely used for sterilization and disinfection. The aim of this study was to examine whether exposure to subinhibitory biocide concentrations influenced transcriptional expression of genes that could improve a pathogen's drug resistance or fitness. We used DNA microarrays to investigate the transcriptome of the uropathogenic Escherichia coli strain CFT073 in response to prolonged exposure to subinhibitory concentrations of four biocides: benzalkonium chloride, chlorhexidine, hydrogen peroxide and triclosan. Transcription of a gene involved in polymyxin resistance, arnT, was increased after treatment with benzalkonium chloride. However, pretreatment of the bacteria with this biocide did not result in cross-resistance to polymyxin in vitro. Genes encoding products related to transport formed the functional group that was most affected by biocides, as 110 out of 884 genes in this category displayed altered transcription. Transcripts of genes involved in cysteine uptake, sulfate assimilation, dipeptide transport, as well as cryptic phage genes were also more abundant in response to several biocides. Additionally, we identified groups of genes with transcription changes unique to single biocides that might include potential targets for the biocides. The biocides did not increase the resistance potential of the pathogen to other antimicrobials. | 2019 | 31569631 |
| 8940 | 15 | 0.9996 | Construction of aminoglycoside-sensitive Burkholderia cenocepacia strains for use in studies of intracellular bacteria with the gentamicin protection assay. Burkholderia cenocepacia is a multidrug-resistant opportunistic pathogen that infects the airways of patients with cystic fibrosis (CF) and can survive intracellularly in macrophages and epithelial cells. The gentamicin protection assay, which relies on the poor ability of gentamicin or other aminoglycosides to permeate eukaryotic cell membranes, is traditionally employed to quantify intracellular bacteria. However, the high resistance of these bacteria to aminoglycosides hampers the use of the gentamicin protection assay to investigate intracellular infection by B. cenocepacia. Here, we report the construction of gentamicin-sensitive strains of B. cenocepacia carrying a deletion of the BCAL1674, BCAL1675, and BCAL1676 genes that form an operon encoding an AmrAB-OprA-like efflux pump. We show that bacteria carrying this deletion are hypersensitive to gentamicin and also delay phagolysosomal fusion upon infection of RAW 264.7 murine macrophages, as previously demonstrated for the parental strain. We also demonstrate for the first time that low concentrations of gentamicin can be used to effectively kill extracellular bacteria and reliably quantify the intracellular infection by B. cenocepacia, which can replicate in RAW 264.7 macrophages. | 2010 | 20348312 |
| 8943 | 16 | 0.9996 | Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses. BACKGROUND: Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E. coli, Salmonella does not produce indole because it does not harbor tnaA, which encodes the enzyme responsible for tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned medium and indole induce expression of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium for inter-species communication; however, the global effect of indole on genes in Salmonella remains unknown. RESULTS: To understand the complete picture of genes regulated by indole, we performed DNA microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC 14028s affected by indole. Predicted Salmonella phenotypes affected by indole based on the microarray data were also examined in this study. Indole induced expression of genes related to efflux-mediated multidrug resistance, including ramA and acrAB, and repressed those related to host cell invasion encoded in the Salmonella pathogenicity island 1, and flagella production. Reduction of invasive activity and motility of Salmonella by indole was also observed phenotypically. CONCLUSION: Our results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica. | 2012 | 22632036 |
| 6322 | 17 | 0.9995 | A soxRS-constitutive mutation contributing to antibiotic resistance in a clinical isolate of Salmonella enterica (Serovar typhimurium). The soxRS regulon is activated by redox-cycling drugs such as paraquat and by nitric oxide. The >15 genes of this system provide resistance to both oxidants and multiple antibiotics. An association between clinical quinolone resistance and elevated expression of the soxRS regulon has been observed in Escherichia coli, but this association has not been explored for other enteropathogenic bacteria. Here we describe a soxRS-constitutive mutation in a clinical strain of Salmonella enterica (serovar Typhimurium) that arose with the development of resistance to quinolones during treatment. The elevated quinolone resistance in this strain derived from a point mutation in the soxR gene and could be suppressed in trans by multicopy wild-type soxRS. Multiple-antibiotic resistance was also transferred to a laboratory strain of S. enterica by introducing the cloned mutant soxR gene from the clinical strain. The results show that constitutive expression of soxRS can contribute to antibiotic resistance in clinically relevant S. enterica. | 2001 | 11120941 |
| 9038 | 18 | 0.9995 | Molecular mechanisms of chlorhexidine tolerance in Burkholderia cenocepacia biofilms. The high tolerance of biofilm-grown Burkholderia cepacia complex bacteria against antimicrobial agents presents considerable problems for the treatment of infected cystic fibrosis patients and the implementation of infection control guidelines. In the present study, we analyzed the tolerance of planktonic and sessile Burkholderia cenocepacia J2315 cultures and examined the transcriptional response of sessile cells to treatment with chlorhexidine. At low (0.0005%) and high (0.05%) concentrations, chlorhexidine had a similar effect on both populations, but at intermediate concentrations (0.015%) the antimicrobial activity was more pronounced in planktonic cultures. The exposure of sessile cells to chlorhexidine resulted in an upregulation of the transcription of 469 (6.56%) and the downregulation of 257 (3.59%) protein-coding genes. A major group of upregulated genes in the treated biofilms encoded membrane-related and regulatory proteins. In addition, several genes coding for drug resistance determinants also were upregulated. The phenotypic analysis of RND (resistance-nodulation-division) efflux pump mutants suggests the presence of lifestyle-specific chlorhexidine tolerance mechanisms; efflux system RND-4 (BCAL2820-BCAL2822) was more responsible for chlorhexidine tolerance in planktonic cells, while other systems (RND-3 [BCAL1672-BCAL1676] and RND-9 [BCAM1945-BCAM1947]) were linked to resistance in sessile cells. After sessile cell exposure, multiple genes encoding chemotaxis and motility-related proteins were upregulated in concert with the downregulation of an adhesin-encoding gene (BCAM2143), suggesting that sessile cells tried to escape the biofilm. We also observed the differential expression of 19 genes carrying putative small RNA molecules, indicating a novel role for these regulatory elements in chlorhexidine tolerance. | 2011 | 21357299 |
| 6185 | 19 | 0.9995 | Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). The activity of tigecycline, 9-(t-butylglycylamido)-minocycline, against Escherichia coli KAM3 (acrB) strains harboring plasmids encoding various tetracycline-specific efflux transporter genes, tet(B), tet(C), and tet(K), and multidrug transporter genes, acrAB, acrEF, and bcr, was examined. Tigecycline showed potent activity against all three Tet-expressing, tetracycline-resistant strains, with the MICs for the strains being equal to that for the host strain. In the Tet(B)-containing vesicle study, tigecycline did not significantly inhibit tetracycline efflux-coupled proton translocation and at 10 microM did not cause proton translocation. This suggests that tigecycline is not recognized by the Tet efflux transporter at a low concentration; therefore, it exhibits significant antibacterial activity. These properties can explain its potent activity against bacteria with a Tet efflux resistance determinant. Tigecycline induced the Tet(B) protein approximately four times more efficiently than tetracycline, as determined by Western blotting, indicating that it is at least recognized by a TetR repressor. The MICs for multidrug efflux proteins AcrAB and AcrEF were increased fourfold. Tigecycline inhibited active ethidium bromide efflux from intact E. coli cells overproducing AcrAB. Therefore, tigecycline is a possible substrate of AcrAB and its close homolog, AcrEF, which are resistance-modulation-division-type multicomponent efflux transporters. | 2004 | 15155219 |