Responses of Wild-Type and Resistant Strains of the Hyperthermophilic Bacterium<i>Thermotoga maritima</i>to Chloramphenicol Challenge

Montero, Clemente I.; Johnson, Matthew R.; Chou, Chin Cheng; Conners, Shannon B.; Geouge, Sarah G.; Tachdjian, Sabrina; Nichols, Jason M.; Kelly, Robert M.

doi:10.1128/aem.00453-07

Cited by 20 publications

(15 citation statements)

References 78 publications

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“…It is a bacteriostatic agent, occasionally also with bactericidal activity, that binds to the 50S ribosomal subunit and blocks the elongation of peptides during the biosynthesis of proteins (39,56). The response to treatments with chloramphenicol in sensitive clinical strains such as Streptococcus pneumoniae (42), Bacillus subtilis (31), Yersinia pestis (51), and Enterococcus faecalis (1) has been analyzed, and it was shown that in addition to protein biosynthesis inhibition, chloramphenicol provokes oxidative stress in sensitive bacteria (1,3).…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms of Resistance to Chloramphenicol in Pseudomonas putida KT2440

Fernández

Conde

Torre

et al. 2012

Antimicrob Agents Chemother

104

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Pseudomonas putida KT2440 is a chloramphenicol-resistant bacterium that is able to grow in the presence of this antibiotic at a concentration of up to 25 g/ml. Transcriptomic analyses revealed that the expression profile of 102 genes changed in response to this concentration of chloramphenicol in the culture medium. The genes that showed altered expression include those involved in general metabolism, cellular stress response, gene regulation, efflux pump transporters, and protein biosynthesis. Analysis of a genome-wide collection of mutants showed that survival of a knockout mutant in the TtgABC resistance-nodulation-division (RND) efflux pump and mutants in the biosynthesis of pyrroloquinoline (PQQ) were compromised in the presence of chloramphenicol. The analysis also revealed that an ABC extrusion system (PP2669/PP2668/PP2667) and the AgmR regulator (PP2665) were needed for full resistance toward chloramphenicol. Transcriptional arrays revealed that AgmR controls the expression of the pqq genes and the operon encoding the ABC extrusion pump from the promoter upstream of open reading frame (ORF) PP2669.

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Section: Discussionmentioning

confidence: 99%

“…Resistance to chloramphenicol may also be due to target site mutation/modification (39), decreased outer membrane permeability (10), and the presence of efflux pumps that often act as multidrug extrusion transporters, thereby reducing the effective intracellular drug concentration (15,53).…”

mentioning

confidence: 99%

Mechanisms of Resistance to Chloramphenicol in Pseudomonas putida KT2440

Fernández

Conde

Torre

et al. 2012

Antimicrob Agents Chemother

104

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“…Although the peptidyl transferase centre is the main target site for many antibiotics and substrate analogs (Spahn & Prescott, 1996), chloramphenicol binds to the 23S rRNA of the 50S ribosomal subunit and blocks the elongation of peptides during biosynthesis of proteins (Montero et al, 2007). Chloramphenicol induces oxida- (Aakra et al, 2010), while β-lactams interfere with the production of peptidoglycan and break the cell of active dividing microorganisms in an iso-osmotic environment (Yellanki et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…These resistance mechanisms may include altered penicillinbinding proteins, presence of various β-lactamases and loss of porins (Bou & Martïnez-Beltran, 2000). While active efflux and enzymatic inactivation are the mechanisms responsible for resistance to aminoglycosides (Smith et al, 2007), the most common mechanisms of resistance to chloramphenicol are decreased outer membrane permeability (Burns et al, 1989), enzymatic inactivation by acetylation essentially by acetyltransferase or by chloramphenicol phosphotransferases (Schwartz et al, 2004;Aakra et al, 2010), target site modulation (Montero et al, 2007) and presence of efflux pump (Daniels & Ramos, 2009). To overcome various resistance mechanisms and dissemination of antibiotic resistance genes, exploring the possible synergy between conventional antibiotics becomes necessary.…”

Section: Introductionmentioning

confidence: 99%

Effects and time-kill assessment of amoxicillin used in combination with chloramphenicol against bacteria of clinical importance

2017

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With the emergence of multidrug-resistant organisms in an era when drug development faces challenges causing pharmaceutical companies to curtail or abandon research on anti-infective agents, the use of combined existing antimicrobial agents may be an alternative. This study evaluated the effects of combining amoxicillin and chloramphenicol, to which many bacteria have become resistant, in vitro against Gram positive and Gram negative bacteria by agar diffusion, checkerboard and time-kill assays. The test isolates were susceptible to amoxicillin with minimum inhibitory concentrations (MICs) ranging between 0.448 and 500 µg/ml and between 1.953 and 31.25 µg/ml for chloramphenicol. Upon combining these agents, there was a drastic reduction in their MICs indicating an increased antibacterial activity that showed synergistic interaction against all the bacteria. At the highest concentrations, the inhibition zones ranges were 20.33-38.33±0.58 µg/ml for amoxicillin, 27.67-37.67±0.58 µg/ml for chloramphenicol and 31.67-39.33±0.58 µg/ml for the combined agents. The fractional inhibitory concentration indices (FICIs) showed synergy ranging from 0.129 to 0.312 while FICIs for additive interaction were between 0.688 and 1.0. There was no antagonistic interaction. At the /MICs of the combined antibiotics, all the tested bacteria, except for Klebsiella pneumoniae ATCC 4352, Proteus vulgaris CSIR 0030 and Enterococcus cloacae ATCC 13047 were eliminated before 24 h. At the MICs, all the tested bacteria were eliminated except Enterococcus cloacae ATCC 13047 which was almost totally eliminated. Post-antibiotic assessment after 48 h showed that all the cultures were sterile except for that of Enterococcus cloacae ATCC 13047. The lack of antagonism between these antibacterial agents in checkerboard and time-kill assays suggested that combining amoxicillin with chloramphenicol can provide an improved therapy in comparison to the use of each antibiotic individually. The study indicates the potential beneficial value of combining amoxicillin and chloramphenicol in the treatment of microbial infections in clinical settings.

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“…For example, spontaneous mutation characteristics in target genes in Thermusthermophilus (a bacterium) and Sulfolobusacidocaldarius (an archaeon) were found to be comparable, despite the phylogenetic and physiological differences that exist between the two microorganisms (Mackwan et al 2008). Also, a chloramphenicol-resistant, mutant of the hyperthermophilic bacterium Thermotogamaritima containedseveral nucleotide changes in ribosomal genes, resulting in significant transcriptomic differences between the mutant and wild-type during growth in the presence and absence of the antibiotic (Montero et al 2007). Mutations were identified in a laboratory strain of the hyperthermophilicarchaeon, Pyrococcusfuriosus DSM 3638(Bridger et al 2012).…”

Section: Introductionmentioning

confidence: 99%

A mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus, lacking flagella, has unusual growth physiology

et al. 2014

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A mutant(‘lab strain’) of the hyperthermophilicarchaeonPyrococcusfuriosusDSM3638 exhibited an extended exponential phase andatypical cell aggregation behavior. Genomic DNA from the mutant culturewas sequenced and compared to wild-type (WT) DSM3638, revealing145genes with one or more insertions, deletions, or substitutions (12 silent, 33amino acid substitutions, and 100 frame-shifts). Approximately half of the mutated genes weretransposases or hypothetical proteins.The WT transcriptomerevealednumerous changes in amino acid and pyrimidine biosynthesis pathways coincidental with growth phase transitions, unlike the mutant whose transcriptome reflected the observedprolonged exponential phase. Targeted gene deletions,based on frame-shifted ORFs in the mutant genome, in a genetically tractable strain of P. furiosus (COM1) could not generate the extended exponential phase behavior observed for the mutant. For example, a putative radical SAM family protein (PF2064) was the most highly up-regulated ORF (>25-fold) in the WT between exponential and stationary phase, although this ORF was unresponsive in the mutant; deletion of this gene in P. furiosus COM1 resulted in no apparent phenotype. On the other hand, frame-shifting mutations in the mutantgenome negatively impacted transcription ofa flagellar biosynthesis operon (PF0329-PF0338).Consequently, cells in the mutant culture lacked flagella and, unlike the WT, showed minimal evidence of exopolysaccharide-based cell aggregation in post-exponential phase. Electron microscopyofPF0331-PF0337 deletionsin P. furiosus COM1 showed that absence of flagella impacted normal cell aggregation behavior and, furthermore,indicatedthat flagella play a key role, beyond motility, in thegrowthphysiology ofP. furiosus.

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Responses of Wild-Type and Resistant Strains of the Hyperthermophilic BacteriumThermotoga maritimato Chloramphenicol Challenge

Cited by 20 publications

References 78 publications

Mechanisms of Resistance to Chloramphenicol in Pseudomonas putida KT2440

Mechanisms of Resistance to Chloramphenicol in Pseudomonas putida KT2440

Effects and time-kill assessment of amoxicillin used in combination with chloramphenicol against bacteria of clinical importance

A mutant (‘lab strain’) of the hyperthermophilic archaeon Pyrococcus furiosus, lacking flagella, has unusual growth physiology

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