Bacterial Death Comes Full Circle: Targeting Plasmid Replication in Drug‐Resistant Bacteria

DeNap, Johna C. B.; Hergenrother, Paul J.

doi:10.1002/chin.200531262

Cited by 10 publications

(12 citation statements)

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“…It has been suggested that activation of TA systems could be an attractive antimicrobial strategy, as the released toxin would kill the host bacterial cell DeNap & Hergenrother, 2005;Gerdes et al, 2005;Alonso et al, 2007;Williams & Hergenrother, 2008). While the presence of TA systems in sequenced prokaryotic genomes has been established, before this work the prevalence of TA systems in clinical isolates of MRSA and PA was unknown.…”

Section: Discussionmentioning

confidence: 98%

“…Exploitation of the inherent toxicity of TA systems has been proposed as a novel antibacterial target, as activation of the latent toxin via direct TA complex disruption or some alternative mechanism would result in bacterial cell death DeNap & Hergenrother, 2005;Alonso et al, 2007;Williams & Hergenrother, 2008). However, a prerequisite for the success of this strategy is the identification of clinically important bacteria that would be susceptible to a compound that activates TA systems.…”

Section: Introductionmentioning

confidence: 99%

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Toxin-antitoxin (TA) systems are prevalent and transcribed in clinical isolates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

Williams

Halvorsen

Dwyer

et al. 2011

FEMS Microbiology Letters

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The percentage of bacterial infections refractory to standard antibiotic treatments is steadily increasing. Among the most problematic hospital and community-acquired pathogens are methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA). One novel strategy proposed for treating infections of multidrug resistant bacteria is the activation of latent toxins of toxin-antitoxin (TA) protein complexes residing within bacteria; however, the prevalence and identity of TA systems in clinical isolates of MRSA and PA has not been defined. We isolated DNA from 78 MRSA and 42 PA clinical isolates and used PCR to probe for the presence of various TA loci. Our results showed that the genes for homologs of the mazEF TA system in MRSA, and the relBE and higBA TA systems in P. aeruginosa were present in 100% of the respective strains. Additionally, RT-PCR analysis revealed that these transcripts are produced in the clinical isolates. These results indicate that TA genes are prevalent and transcribed within MRSA and PA and suggest that activation of the toxin proteins could be an effective antibacterial strategy for these pathogens.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Toxin-antitoxin (TA) systems are prevalent and transcribed in clinical isolates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

Williams

Halvorsen

Dwyer

et al. 2011

FEMS Microbiology Letters

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“…Identification and classification of plasmids should be based on genetic traits that are present and constant. These criteria are best met by traits concerned with plasmid maintenance, especially replication controls (DeNap and Hergenrother, 2005). In 1971 Datta and Hedges proposed a plasmid classification scheme based on the stability of plasmids during conjugation, a phenomenon called plasmid incompatibility (Datta and Hedges, 1971).…”

Section: Detection and Classification Of Plasmids Carrying Esbl And/omentioning

confidence: 99%

Scientific Opinion on the public health risks of bacterial strains producing extended-spectrum β-lactamases and/or AmpC β-lactamases in food and food-producing animals

2011

EFSA Journal

246

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The potential contribution of food-producing animals or foods to public health risks by ESBL and/or AmpCproducing bacteria is related to specific plasmid-mediated ESBL and/or AmpC genes encoded by a number of organisms. The predominant ESBL families encountered are CTX-M, TEM, and SHV; the predominant AmpCfamily is CMY. The most common genes associated with this resistance in animals are bla CTX-M-1 (the most commonly identified ESBL), and bla CTX-M-14 , followed by bla and bla Among the genes encoding AmpC-type β-lactamases, bla CMY-2 is the most common.The bacterial species most commonly identified with these genes are Escherichia coli and non-typhoidal Salmonella. ESBL/AmpC transmission is mainly driven by integrons, insertion sequences, transposons and plasmids, some of which are homologous in isolates from both food-production animals and humans. Cefotaxime is used as the drug of choice for optimum detection of bla ESBL and/or bla AmpC genes. The preferred method for isolation of ESBL-and/or AmpC-producers is screening on selective agar preceded by selective enrichment in a broth.The establishment of risk factors for occurrence of ESBL/AmpC-producing bacteria is particularly complicated by the data unavailability or lack of its accuracy. The use of antimicrobials is a risk factor for the selection and spread of resistant clones, resistance genes and plasmids. Since most ESBL-and AmpC-producing strains carry additional resistances to other commonly-used veterinary drugs, generic antimicrobial use is a risk factor for ESBL/AmpC and it is not restricted specifically to the use of cephalosporins. An additional risk factor is extensive trade of animals in EU MS. There are no data on the comparative efficiency of individual control options in reducing public health risks caused by ESBL and/or AmpC-producing bacteria related to food-producing animals. Prioritisation is complex, but it is considered that a highly effective control option would be to stop all uses of cephalosporins/systemically active 3 rd /4 th generation cephalosporins, or to restrict their use (use only allowed under specific circumstances). As co-resistance is an important issue, it is also of high priority to decrease the total antimicrobial use in animal production in the EU. KEY WORDSResistance, ESBLs, AmpC, occurrence, transmission, control options, public health microbiology. SUMMARYFollowing a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a Scientific Opinion on the public health risks of bacterial strains producing extended-spectrum beta (β)-lactamases (ESBL) and/or AmpC β-lactamases (AmpC) in food and foodproducing animals. In particular, the Panel was asked: (i) to propose a definition of the ESBL-and/or AmpC-producing bacterial strains and genes relevant for public health and linked to food-producing animals or food borne transmission; (ii) to review the information on the epidemiology of acquired resistance to broad spectrum cephalosporins including the genes coding for ...

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“…49,50 Furthermore, antibiotic nonsusceptibility is not always a clear one-to-one relationship between antibiotic exposure and resistance to that same antibiotic, but is likely complicated by bacterial acquisition of plasmids that often confer resistance to multiple antibiotics. [51][52][53] Finally, macrolide use in the private clinics may have contributed to penicillin resistance despite low levels of reported penicillin use. [54][55][56] S. pneumoniae serotypes/groups 19, 23, and 6 were the most commonly isolated, and a small percentage of each group was nonsusceptible to all four antibiotics tested.…”

Section: Discussionmentioning

confidence: 99%

Increasing penicillin and trimethoprim–sulfamethoxazole resistance in nasopharyngeal Streptococcus pneumoniae isolates from Guatemalan children, 2001–2006

Dueger

Asturias

Matheu

et al. 2008

International Journal of Infectious Diseases

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Bacterial Death Comes Full Circle: Targeting Plasmid Replication in Drug‐Resistant Bacteria

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 10 publications

References 1 publication

Toxin-antitoxin (TA) systems are prevalent and transcribed in clinical isolates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

Toxin-antitoxin (TA) systems are prevalent and transcribed in clinical isolates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus

Scientific Opinion on the public health risks of bacterial strains producing extended-spectrum β-lactamases and/or AmpC β-lactamases in food and food-producing animals

Increasing penicillin and trimethoprim–sulfamethoxazole resistance in nasopharyngeal Streptococcus pneumoniae isolates from Guatemalan children, 2001–2006

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