A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 β-Lactamase

Marciano, David C.; Karkouti, Omid Y; Palzkill, Timothy

doi:10.1534/genetics.106.069443

Cited by 55 publications

(52 citation statements)

References 63 publications

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“…Alternatively, Marciano et al suggested that the signal peptide of the class A carbapenemase SME-1 might be responsible for cell lysis and plasmid rearrangements in an E. coli strain, either by forming pores on the bacterial cell wall or by hijacking the protein synthesis machinery (33). Whether the signal peptide of VIM-2 is accountable for the deleterious effects observed in S. Typhimurium remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Cordeiro

Chabalgoity

Yim

et al. 2014

Antimicrob Agents Chemother

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Antibiotic resistance, especially due to ␤-lactamases, has become one of the main obstacles in the correct treatment of Salmonella infections; furthermore, antibiotic resistance determines a gain of function that may encompass a biological cost, or fitness reduction, to the resistant bacteria. The aim of this work was to determine in vitro if the production of the class B ␤-lactamase VIM-2 determined a fitness cost for Salmonella enterica serovar Typhimurium. To that end the gene bla VIM-2 was cloned into the virulent strain S. Typhimurium SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid pST12, for inducible and constitutive expression, respectively. Fitness studies were performed by means of motility, growth rate, invasiveness in epithelial cells, and plasmid stability. The expression of bla VIM-2 was accompanied by alterations in micro-and macroscopic morphology and reduced growth rate and motility, as well as diminished invasiveness in epithelial cells. These results suggest that VIM-2 production entails a substantial fitness cost for S. Typhimurium, which in turn may account for the extremely low number of reports of metallo-␤-lactamase-producing Salmonella spp.

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Section: Discussionmentioning

confidence: 99%

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Cordeiro

Chabalgoity

Yim

et al. 2014

Antimicrob Agents Chemother

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“…A recent study by Call et al (6) showed that the bla CMY-2 region of pAR060302 is prone to stochastic excision and, in the absence of selection pressure, populations of E. coli harboring bla CMY-2 were outcompeted by bla CMY-2 -lacking plasmids over many generations. Other studies have shown a significant cost of carrying other variants of AmpC-like ␤-lactamase genes (18,26). It was hypothesized that this cost is a result of unregulated expression and that this cost of carriage results in reduced dissemination.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Mapping of pAR060302, a bla _CMY-2 -Positive Broad-Host-Range IncA/C Plasmid

Lang

Danzeisen

et al. 2012

Appl Environ Microbiol

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The multidrug resistance-encoding plasmids belonging to the IncA/C incompatibility group have recently emerged among Escherichia coli and Salmonella enterica strains in the United States. These plasmids have a unique genetic structure compared to other enterobacterial plasmid types, a broad host range, and a propensity to acquire large numbers of antimicrobial resistance genes via their accessory regions. Using E. coli strain DH5␣ harboring the prototype IncA/C plasmid pAR060302, we sought to define the baseline transcriptome of IncA/C plasmids under laboratory growth and in the face of selective pressure. The effects of ampicillin, florfenicol, or streptomycin exposure were compared to those on cells left untreated at logarithmic phase using Illumina platform-based RNA sequencing (RNA-Seq). Under growth in Luria-Bertani broth lacking antibiotics, much of the backbone of pAR060302 was transcriptionally inactive, including its putative transfer regions. A few plasmid backbone genes of interest were highly transcribed, including genes of a putative toxin-antitoxin system and an H-NS-like transcriptional regulator. In contrast, numerous genes within the accessory regions of pAR060302 were highly transcribed, including the resistance genes floR, bla CMY-2 , aadA, and aacA. Treatment with ampicillin or streptomycin resulted in no genes being differentially expressed compared to controls lacking antibiotics, suggesting that many of the resistance-associated genes are not differentially expressed due to exposure to these antibiotics. In contrast, florfenicol treatment resulted in the upregulation of floR and numerous chromosomal genes. Overall, the transcriptome mapping of pAR060302 suggests that it mitigates the fitness costs of carrying resistance-associated genes through global regulation with its transcriptional regulators.

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“…Genes whose presence significantly reduces cell fitness are rapidly lost in the absence of selection, whereas those that come at a low cost can stably persist in the cells, even when pathogens are not exposed to antibiotics (1,3,10,18,23,24,35,44). Therefore, knowing the fitness cost of a resistance mechanism is important for predicting the efficiency of its maintenance and the rate of expansion.…”

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Low Fitness Cost of the Multidrug Resistance Gene cfr

LaMarre

Locke

Shaw

et al. 2011

Antimicrob Agents Chemother

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The recently described rRNA methyltransferase Cfr that methylates the conserved 23S rRNA residue A2503, located in a functionally critical region of the ribosome, confers resistance to an array of ribosomal antibiotics, including linezolid. A number of reports of linezolid-resistant cfr-positive clinical strains indicate the possible rapid spread of this resistance mechanism. Since the rate of dissemination and the efficiency of maintenance of a resistance gene depend on the fitness cost associated with its acquisition, we investigated the fitness cost of cfr expression in a laboratory Staphylococcus aureus strain. We found that acquisition of the cfr gene does not produce any appreciable reduction in the cell growth rate. Only in a cogrowth competition experiment was some loss of fitness observed because Cfr-expressing cells slowly lose to the cfr-negative control strain. Interestingly, cells expressing wild-type and catalytically inactive Cfr had very similar growth characteristics, indicating that the slight fitness cost associated with cfr acquisition stems from expression of the Cfr polypeptide rather than from the modification of the conserved rRNA residue. In some clinical isolates, cfr is coexpressed with the erm gene, which encodes a methyltransferase targeting another 23S rRNA residue, A2058. Dimethylation of A2058 by Erm notably increases the fitness cost associated with the Cfr-mediated methylation of A2503. The generally low fitness cost of cfr acquisition observed in our experiments with the laboratory S. aureus strain offers a microbiological explanation for the apparent spread of the cfr gene among pathogens.

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A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 β-Lactamase

Cited by 55 publications

References 63 publications

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Transcriptome Mapping of pAR060302, a bla _CMY-2 -Positive Broad-Host-Range IncA/C Plasmid

Low Fitness Cost of the Multidrug Resistance Gene cfr

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A Fitness Cost Associated With the Antibiotic Resistance Enzyme SME-1 β-Lactamase

Cited by 55 publications

References 63 publications

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Transcriptome Mapping of pAR060302, a bla CMY-2 -Positive Broad-Host-Range IncA/C Plasmid

Low Fitness Cost of the Multidrug Resistance Gene cfr

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Transcriptome Mapping of pAR060302, a bla _CMY-2 -Positive Broad-Host-Range IncA/C Plasmid