Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of
            <i>Staphylococcus aureus</i>

DeMarco, Carmen E.; Cushing, Laurel A.; Frempong-Manso, Emmanuel; Seo, Susan M.; Jaravaza, Tinevimbo A. A.; Kaatz, Glenn W.

doi:10.1128/aac.00430-07

Cited by 185 publications

(174 citation statements)

References 31 publications

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“…For example, 1-(1-napthhylmethyl)-piperazine potentiates the effect of tetracycline in A. baumannii, but it increases the resistance of this pathogen to the more clinically relevant antibiotic tigecycline (17). EPIs have contributed substantially to studies of the involvement of efflux pumps in the resistance of clinical isolates (50,125), by demonstrating their ability to reverse resistance. However, a recent study found that reserpine did not accurately predict the overexpression of efflux pumps in Staphylococcus (66).…”

Section: Negating Efflux Pump Activitymentioning

confidence: 99%

Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

2012

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SUMMARY The substantial use of antibiotics in the clinic, combined with a dearth of new antibiotic classes, has led to a gradual increase in the resistance of bacterial pathogens to these compounds. Among the various mechanisms by which bacteria endure the action of antibiotics, those affecting influx and efflux are of particular importance, as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. This review evaluates the impact of porins and efflux pumps on two major types of resistance, namely, mutational and adaptive types of resistance, both of which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms. In particular, we explain how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics. The identification of porins and pumps as major resistance markers has opened new possibilities for the development of novel therapeutic strategies directed specifically against these mechanisms.

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Section: Negating Efflux Pump Activitymentioning

confidence: 99%

Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

2012

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“…The role of an MDR efflux-related increase in 301 MIC and skin disinfection with CH is also discussed by DeMarco et al [33]. Efflux mechan-302 isms are also relevant for decreasing susceptibility, for example of Treponema denticola, to 303 hBD-3 [34], although current research findings suggest that MDR efflux pumps do not play 304 an important role in hBD-3-resistance [35].…”

mentioning

confidence: 50%

Skin bacteria after chlorhexidine exposure—is there a difference in response to human β-Defensin-3?

Reichel

Heisig

et al. 2010

Eur J Clin Microbiol Infect Dis

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Purpose:We investigated whether exposure to sub-lethal concentrations of chlorhexidine digluconate (CH) changed the response of 5 Staphylococcus spp. to human β-Defensin-3. Methods:The change in response for each strain was determined in-vitro with time-kill-experiments in suspension by comparing the mean log10-reduction caused by hBD-3 at 1.5 and 3 h in exposed and non-exposed bacteria. Identity of staphylococcal species was verified by DNA sequence homology in the gyrA genes in comparison with reference strains.Results: Baseline sub-lethal concentrations allowing visible bacterial growth were between 0.0625 and 0.25 μg/ml. Sub-lethal CH concentrations increased within 3 days in two isolates. For Staphylococcus capitis 19/2, CH-exposed cells were less susceptible to 0.5 μg/ml hBD-3 (log10-reduction 0.78 versus 2.06 at 1.5 h; p <0.001; t-test). For Staphylococcus aureus, however, CH-exposed cells were more susceptible to 1 μg/ml hBD-3. The observed changes between CH-exposed and non-exposed cells did not indicate a general trend in response to hBD-3. Conclusions:Overall, we found no consistent evidence that 3 days of exposure to CHG changed the response of 5 Staphylococcus spp. to hBD-3. The use of CHG for skin antisepsis is, based on our data, unlikely to change the natural defence activity of hBD-3.Response to Reviewers: REVIEWER #1:Major points:Reviewer comment: Human beta-defensin-3 is a very sticky peptide. To minimize losses, cationic antimicrobial peptides are usually dissolved in weakly acidic solvents. The authors used water, which could influence losses of the peptide and thus might influence its concentration in the remaining solution.Response: We were aware that some studies were published with hBD-3 using acetic acid for dissolving the peptide, but the manufacturer (RELIATech) confirmed that their hBD-3 should be reconstituted in water, that it can also be diluted in water and that the use of water will not change the activity of the peptide which was used for the test. That was the reason why we used water (pH-value between 6.5 and 6.8).Reviewer comment: Did the authors pool the beta-defensin-3? If yes, did they use the material at exactly identical conditions (e.g. storage at ambient temperature or in the refrigerator after thawing). If not, one would expect variable results.Response: Whenever necessary, we pooled aliquots of the diluted peptide after thawing. We did not pool different batches because we only used one batch of the peptide. Nevertheless, we used cooled metal blocks for the storage of the peptide after thawing to ensure that the con-ditions did not change between tests.The part in the Methods section of the manuscript was amended to clarify the questions of the reviewer.Reviewer comment: Could the authors reproduce in independent experiments (with another peptide sample) the results they found in the four cases where hBD-3 killed significantly fewer bacteria?Response: It is a very interesting question if the decrease of the sensitivity of the strain to hBD-3 could also be ...

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“…A number of methods have been used to identify the efflux systems in bacteria including use of radio labelled substrates, fluorometric assays or the determination of the MIC in the presence of efflux inhibitors (DeMarco et al, 2007;Patel et al, 2010;Kaatz et al, 2000). In our work from 13 clinical isolates only 8 isolates (61.5%) were found to be NorA and NorB efflux pumps positive.…”

Section: Discussionmentioning

confidence: 75%

“…In our work from 13 clinical isolates only 8 isolates (61.5%) were found to be NorA and NorB efflux pumps positive. A previous work reported 49% prevalence of NorB type efflux pump among S. aureus clinical isolates recovered from blood (DeMarco et al, 2007). Another study also demonstrated occurrence of NorB, MdeA or MepA type efflux pumps in S. aureus (Costa et al, 2011).…”

Section: Discussionmentioning

confidence: 76%

Evaluation of Different Drugs in Down-Regulation of Efflux Pump Genes expression in Methicillin-Resistant <I>Staphylococcus aureus</I> Strains

Chaudhary¹,

Patnaik²,

Payasi³

2014

American Journal of Infectious Diseases

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Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

Cited by 185 publications

References 31 publications

Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

Skin bacteria after chlorhexidine exposure—is there a difference in response to human β-Defensin-3?

Evaluation of Different Drugs in Down-Regulation of Efflux Pump Genes expression in Methicillin-Resistant <I>Staphylococcus aureus</I> Strains

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