Transferable resistance to cefoxitin in Bacteroides thetaiotaomicron

Rashtchian, Ayoub; Dubes, George R.; Booth, Samuel

doi:10.1128/aac.22.4.701

Cited by 20 publications

(10 citation statements)

References 13 publications

(6 reference statements)

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“…This is uncharacteristic of commonly described beta-lactamases of the B. fragilis group which inactivate cephalosporins at higher rates than penicillins and represents the acquisition of a qualitatively different resistance mechanism transfer capability (18,22). Finally, cefoxitin resistance transfer has been reported in a strain of B. thetaiotaomicron by Rashtchian et al (16). However, the mechanism of the resistance in this isolate was not determined.…”

Section: Resultsmentioning

confidence: 99%

Cefoxitin inactivation by Bacteroides fragilis

Cuchural¹,

Tally²,

Jacobus³

et al. 1983

Antimicrob Agents Chemother

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We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of 264 Ug/lml. These isolates were also resistant to other beta-lactam antibiotics. Of 11 isolates, 4 were able to inactivate cefoxitin in broth cultures, as measured by microbiological and high-pressure liquid chromatography assays. Two distinct patterns of cefoxitin breakdown products were detected by high-pressure liquid chromatography analysis. The beta-lactamase inhibitors clavulanic acid and sulbactam failed to show synergism with cefoxitin. These data demonstrate that members of the B.fragilis group have acquired a novel resistance mechanism enabling them to inactivate cefoxitin.Cefoxitin possesses excellent in vitro activity against the Bacteroides fragilis group of organisms (20) and has been shown to be efficacious in the treatment of mixed aerobic and anaerobic infections involving these pathogens (21). The B. fragilis group, which includes: B. fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, and Bacteroides vulgatus, is resistant to many commonly used antimicrobial agents including penicillins and cephalosporins. Bacteroides uniformis has recently been considered with the B. fragilis group because of similar susceptibilities. These organisms are known to possess beta-lactamases which inactivate most of the first and second generation cephalosporins and penicillins (18,22). Of the currently available beta-lactam antibiotics, cefoxitin has the best in vitro activity (4,19). The enhanced activity of cefoxitin against these pathogens has been attributed to the resistance of the drug to the beta-lactamases of B. fragilis (3,5,7,11,22). Although there have been rare reports documenting the inactivation of the drug, the most common reported mechanism of cefoxitin resistance in this group of organisms has been the failure of the drug to penetrate through the outer membrane (6).Our laboratory has been the reference center for a multicenter study of the susceptibility of the B. fragilis group of organisms in the United States (19

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Section: Resultsmentioning

confidence: 99%

Cefoxitin inactivation by Bacteroides fragilis

Cuchural¹,

Tally²,

Jacobus³

et al. 1983

Antimicrob Agents Chemother

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“…B. fragilis strain TAL4 170 was shown to transfer P-lactamase-mediated cefoxitin resistance to a susceptible B. fragilis recipient by conjugation [90]. Also, cefoxitin resistance transfer has been demonstrated in a strain of B. thetaiotaomicron, although the precise resistance mechanism for this isolate was not determined [91].…”

Section: P-lactamasesmentioning

confidence: 99%

Resistance to -Lactam Antibiotics in Bacteroides Spp.

Edwards¹

1997

Journal of Medical Microbiology

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Bacteroides spp., particularly B. fragilis, are well-recognised bacterial pathogens. Production of the typical P-lactamases of Bacteroides restricts the therapeutic use of P-lactam agents mainly to the P-lactamase inhibitor combinations and carbapenems. These compounds have the advantage of broad-spectrum activity and the ability to combat polymicrobial infections. Resistance of Bacteroides spp. to P-lactam antibiotics appears to be increasing, largely because of an overall increase in P-lactamase activity. There has been a rise in the prevalence of isolates showing high-level production of typical Bacteroides P-lactamases and an increase in reports other potent p-lactamase types. In the case of B. fragilis, metallo-enzymes are a particular threat to current therapeutic practice, as they are not inhibited by common P-lactamase inhibitors and are able to hydrolyse carbapenems. The presence of permeability barriers may confer low-level p-lactam resistance and supplement the effect of P-lactamase activity. There are also sporadic reports of loss of /?-lactam activity because of reduced affinity of the penicillin-binding proteins.

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confidence: 99%

“…In contrast to the transmissible Tcr and erm systems, there is no detailed information available on the genetic elements encoding transmissible 3-lactam resistance. In previous reports, plasmid-free transfer of cefoxitin (FX) resistance was observed, but there was no further characterization of the determinants responsible for transfer (6,24,26).Recently, we described the cloning and nucleotide sequence analysis of a novel, widely disseminated P-lactamase gene (cfr4) encoding Fxr in Bacteroides species (21). This resistance gene is not plasmid encoded, but preliminary evidence showed that the resistance phenotype was transmissible when donor cells were grown in the presence of TC 2682…”

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Identification of a circular intermediate in the transfer and transposition of Tn4555, a mobilizable transposon from Bacteroides spp

Smith

Parker

1993

J Bacteriol

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Transmissible cefoxitin (FX) resistance in Bacteroides vulgatus CLA341 was associated with the 12.5-kb, mobilizable transposon, Tn4555, which encoded the 13-lactamase gene cfxA. Transfer occurred by a conjugation-like mechanism, was stimulated by growth of donor cells with tetracycline (TC) [44]) that has arisen in the past few decades. The first studies of Tcr transfer described the unusual effect of TC pretreatment on conjugation frequency, and it was shown that growth of donor cells with TC for five or more generations enhanced transfer frequency severalfold (23). Subsequent studies documented the lack of plasmid involvement in the transfer process (17,19,41), but it became apparent that these chromosomal elements could promote or increase the transfer of plasmids such as pBFTM10, several classes of the small cryptic Bacteroides plasmids, and the nonreplicating Bacteroides units (19,31,32). Thus, the ability of TET elements to enhance gene transfer may play a central role in the dissemination of antibiotic resistance in these organisms.The mechanisms of gene transfer and mobilization in Bacteroides species are not well characterized, and the way in which TC treatment affects these processes is not understood. Very low TC concentrations (0.1 ,ug/ml) did not enhance Tcr transfer in Bacteroides fragilis V479-1 (41), and in Bacteroides uniformis, the production of the nonreplicating Bacteroides units was detected after overnight growth * Corresponding author. with 0.3 pug but not 0.1 jig of TC per ml (32). At the drug concentrations used in these experiments, it is not clear whether the TC effects are due to a true induction or a selection. In this regard, experiments focusing on the temporal expression of TC-enhanced functions have not been done, but two genetic loci, rteA and rteB, responsible for controlling TC-dependent transfer of a TET element, have been identified elsewhere (43). These genes also seem to be required for the TC-dependent appearance of the nonreplicating Bacteroides units, and they appear to be part of a TC signal transduction pathway with homology to two-component regulatory systems.Another Bacteroides conjugation system that has been studied is pBFTM10. Two genes required for efficient transfer of the plasmid, btgA and btgB, were identified and sequenced (12). The protein encoded by btgA possessed a DNA-binding motif, but overall the btgA and btgB gene products had no homology to known transfer proteins from other bacterial systems. However, a region containing a putative nick site and general structural similarity to the oriT of IncP plasmids was identified (12). In contrast to the transmissible Tcr and erm systems, there is no detailed information available on the genetic elements encoding transmissible 3-lactam resistance. In previous reports, plasmid-free transfer of cefoxitin (FX) resistance was observed, but there was no further characterization of the determinants responsible for transfer (6,24,26).Recently, we described the cloning and nucleotide sequence analysis of a novel, wide...

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Transferable resistance to cefoxitin in Bacteroides thetaiotaomicron

Cited by 20 publications

References 13 publications

Cefoxitin inactivation by Bacteroides fragilis

Cefoxitin inactivation by Bacteroides fragilis

Resistance to -Lactam Antibiotics in Bacteroides Spp.

Identification of a circular intermediate in the transfer and transposition of Tn4555, a mobilizable transposon from Bacteroides spp

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