Acquired Inducible Antimicrobial Resistance in Gram-Positive Bacteria

Chancey, Scott; Zähner, Dorothea; Stephens, David S.

doi:10.2217/fmb.12.63

Cited by 99 publications

(73 citation statements)

References 113 publications

(138 reference statements)

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“…Although the operon is transcribed constitutively, it is only upon exposure to Tc that translation occurs (19, 44–46). Similar mechanisms of inducible antibiotic resistance have also been reported for Tc induction in the Enterococcus Tn 916 and related elements, as well as vancomycin induction of the Gram-positive Tn 1546 (47). …”

Section: Ctndot Overviewsupporting

confidence: 70%

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Waters

Salyers

2013

mBio

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CTnDOT is a 65-kb conjugative transposon that is found in Bacteroides spp., which are one of the more abundant members within the lower human gastrointestinal tract. CTnDOT encodes resistance to the antibiotics erythromycin and tetracycline (Tc). An interesting feature of CTnDOT is that exposure to low levels of Tc induces a cascade of events that ultimately results in CTnDOT conjugative transfer. However, Tc is apparently not a switch that activates transfer but rather a signal that appears to override a series of negative regulators that inhibit premature excision and transfer of CTnDOT. In this minireview, we summarize over 20 years of research that focused on elucidating the highly coordinated regulation of excision, mobilization, and transfer of CTnDOT.

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Section: Ctndot Overviewsupporting

confidence: 70%

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Waters

Salyers

2013

mBio

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“…Ribosomesensed induction and efflux-pump activation are examples of mechanisms that initially protect the cell through induction of expression (38) and allow it to survive low levels of antibiotics. Subsequently, mutations are promoted by the SOS response that stimulate the horizontal exchange of resistance genes (11) or stress-induced modulation of genetic instability (39) and result in resistance to higher concentrations.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Mutations and Regulation of Gene Expression during Development of De Novo Antibiotic Resistance

Händel

Schuurmans

Feng

et al. 2014

Antimicrob Agents Chemother

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bBacteria can become resistant not only by horizontal gene transfer or other forms of exchange of genetic information but also by de novo by adaptation at the gene expression level and through DNA mutations. The interrelationship between changes in gene expression and DNA mutations during acquisition of resistance is not well documented. In addition, it is not known whether the DNA mutations leading to resistance always occur in the same order and whether the final result is always identical. The expression of >4,000 genes in Escherichia coli was compared upon adaptation to amoxicillin, tetracycline, and enrofloxacin. During adaptation, known resistance genes were sequenced for mutations that cause resistance. The order of mutations varied within two sets of strains adapted in parallel to amoxicillin and enrofloxacin, respectively, whereas the buildup of resistance was very similar. No specific mutations were related to the rather modest increase in tetracycline resistance. Ribosome-sensed induction and efflux pump activation initially protected the cell through induction of expression and allowed it to survive low levels of antibiotics. Subsequently, mutations were promoted by the stress-induced SOS response that stimulated modulation of genetic instability, and these mutations resulted in resistance to even higher antibiotic concentrations. The initial adaptation at the expression level enabled a subsequent trial and error search for the optimal mutations. The quantitative adjustment of cellular processes at different levels accelerated the acquisition of antibiotic resistance. The de novo acquisition of resistance against antibiotics is known to be accompanied by certain mutations and differential expression of specific genes (1-5). The "radical-based" theory (6, 7) proposes that bactericidal antibiotics cause cell death by a single mechanism, driven by the accumulation of oxygen radicals in the cells. In that case, the cellular response to sublethal concentrations of antibiotics should be similar even for compounds belonging to different classes of bactericidal drugs, such as beta-lactams or fluoroquinolones. The outcome might differ for bacteriostatic drugs, for example, tetracycline. The radical-based theory, however, is the subject of debate (8). The revelation of a common denominator for the adaptation processes to different antibiotics might illuminate the question of a single mechanism from a different angle.Resistance can easily be induced in Escherichia coli by exposure to stepwise increasing sublethal antibiotic concentrations (9). The effects of the acquisition of resistance to amoxicillin on the overall physiology is a complex set of adaptations at the gene expression level, preventing metabolic costs at the expense of the ecological range (10). After the initial stage, the prolonged exposure to antibiotics modulates the SOS response, leading in turn to mutations that cause resistance (11). The mutations generate more permanent resistance, which remains long after the antibiotic pressure has been ...

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“…Antibiotic resistance is defined as the ability of a specific bacterium to survive in the presence of an antibiotic that was originally effective to treat infections caused by the bacterium, or acquisition of a specific antibiotic resistance mechanism[20, 21]. There are four major mechanisms of bacterial antibiotic resistance: production of enzymes that inactivate the drug; production of modified targets against which the antibiotic has a reduced effect; reduction of permeability to the drug; and active export antibiotics using various pumps[22].…”

Section: The Rise Of Antimicrobial Resistancementioning

confidence: 99%

“…Mechanisms of antimicrobial resistance in bacteria. Am J Infect Control 2006,34:S3–10; discussion S64–73, with supplemental information from other sources[20, 102–105]. …”

Section: Figurementioning

confidence: 99%

Antibiotic Use and Emerging Resistance: How Can Resource-Limited Countries Turn the Tide?

2014

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Antibiotic resistance is a global crisis driven by appropriate and inappropriate antibiotic use to treat human illness and promote animal growth. The antimicrobial resistance epidemic continues to spread due to the triple threat of unfettered access, minimal product regulation and oversight of antibiotic prescription, and lack of clinical diagnostic tools to support antibiotic de-escalation in low-resource settings. In high-resource settings, evidence-based strategies have improved appropriateness of antibiotic use, limiting the spread of drug-resistant organisms and reducing hospital-associated infections, which may also be effective to stop the spread of resistance in resource-poor countries. Current research and surveillance efforts on antimicrobial resistance and hospital-associated infections in low-resource settings are extremely limited, largely focused intensive care units. Many challenges exist to improving antibiotic use and infection control in resource-limited settings, and turning the tide requires intensifying research and surveillance, antimicrobial stewardship, and developing new bedside diagnostic tools for bacterial infections and antimicrobial susceptibility.

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Acquired Inducible Antimicrobial Resistance in Gram-Positive Bacteria

Cited by 99 publications

References 113 publications

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Regulation of CTnDOT Conjugative Transfer Is a Complex and Highly Coordinated Series of Events

Interaction between Mutations and Regulation of Gene Expression during Development of De Novo Antibiotic Resistance

Antibiotic Use and Emerging Resistance: How Can Resource-Limited Countries Turn the Tide?

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