Selection of Bacillus anthracis isolates resistant to antibiotics

Athamna, Abed; Athamna, Muhammad; Abu-Rashed, N.; Medlej, B.; Bast, Darrin J.; Rubinstein, Ethan

doi:10.1093/jac/dkh258

Cited by 110 publications

(78 citation statements)

References 11 publications

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“…For example, although penicillin is considered the treatment of choice for all forms of anthrax, many penicillin-resistant strains and treatment failures have been reported in the literature [5][6][7] . Reports of B anthracis resistance to ciprofloxacin and other antibiotics have likewise appeared [8][9][10][11] . It is, therefore, important to reevaluate the spectrum of antibiotics and to develop new drugs that are available for anthrax treatment.…”

Section: Introductionmentioning

confidence: 97%

Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Xing

Wang

Dai³

et al. 2013

Acta Pharmacol Sin

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Aim: To examine whether the novel cyclic lipopeptide antibiotic daptomycin could be used to treat anthrax and to study the mechanisms underlying its bactericidal action against Bacillus anthracis. Methods: Spore-forming B anthracis AP422 was tested. MIC values of antibiotics were determined. Cell membrane potential was measured using flow cytometric assays with membrane potential-sensitive fluorescent dyes. Cell membrane integrity was detected using To-Pro-3 iodide staining and transmission electron microscopy. K + efflux and Na + influx were measured using the fluorescent probes PBFI and SBFI-AM, respectively. Results: Daptomycin exhibited rapid bactericidal activity against vegetative B anthracis with a MIC value of 0.78 μg/mL, which was comparable to those of ciprofloxacin and penicillin G. Furthermore, daptomycin prevented the germinated spores from growing into vegetative bacteria. Daptomycin concentration-dependently dissipated the membrane potential of B anthracis and caused K + efflux and Na + influx without disrupting membrane integrity. In contrast, both ciprofloxacin and penicillin G did not change the membrane potential of vegetative bacteria or spores. Penicillin G disrupted membrane integrity of B anthracis, whereas ciprofloxacin had no such effect. Conclusion: Daptomycin exerts rapid bactericidal action against B anthracis via reducing membrane potential without disrupting membrane integrity. This antibiotic can be used as an alternate therapy for B anthracis infections.

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Section: Introductionmentioning

confidence: 97%

Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Xing

Wang

Dai³

et al. 2013

Acta Pharmacol Sin

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“…In addition, B. anthracis has been shown to be able to acquire resistance to certain antibiotics with relative ease (1,3,5,29). Should infections occur with a resistant strain of B. anthracis that cannot be treated with conventional antibiotics, cell wall-cleaving enzymes such as PlyPH may be considered as an alternative form of therapy.…”

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confidence: 99%

PlyPH, a Bacteriolytic Enzyme with a Broad pH Range of Activity and Lytic Action against Bacillus anthracis

et al. 2006

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“…However, this treatment option may prove ineffective in the face of a bioweaponized B. anthracis strain that is resistant to these drugs. B. anthracis strains have been shown to exhibit significant rates of spontaneous resistance to ciprofloxacin and doxycycline (3,9,26), while high levels of intrinsic resistance to other generally useful antibiotics, such as trimethoprim, further limit alternative methods of treatment (1,5,6,46). Moreover, Soviet scientists are now known to have purposely engineered multiple drug resistance mechanisms into B. anthracis strains intended for bioweapon production (50,60).…”

mentioning

confidence: 99%

Evaluation of the metS and murB Loci for Antibiotic Discovery Using Targeted Antisense RNA Expression Analysis in Bacillus anthracis

Kedar

Brown-Driver

Reyes

et al. 2007

Antimicrob Agents Chemother

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The biowarfare-relevant bacterial pathogen Bacillus anthracis contains two paralogs each of the metS and murB genes, which encode the important antibiotic target functions methionyl-tRNA synthetase and UDP-Nacetylenolpyruvoylglucosamine reductase, respectively. Empirical screens were conducted to detect and characterize gene fragments of each of these four genes that could cause growth reduction of B. anthracis when inducibly expressed from a plasmid-borne promoter. Numerous such gene fragments that were overwhelmingly in the antisense orientation were identified for the metS1 and murB2 alleles, while no such orientation bias was seen for the metS2 and murB1 alleles. Gene replacement mutagenesis was used to confirm the essentiality of the metS1 and murB2 alleles, and the nonessentiality of the metS2 and murB1 alleles, for vegetative growth. Induced transcription of RNA from metS1 and murB2 antisense-oriented gene fragments resulted in specific reduction of mRNA of their cognate genes. Attenuation of MetS1 enzyme expression hypersensitized B. anthracis cells to a MetS-specific antimicrobial compound but not to other antibiotics that affect cell wall assembly, fatty acid biosynthesis, protein translation, or DNA replication. Antisense-dependent reduction of MurB2 enzyme expression caused hypersensitivity to beta-lactam antibiotics, a synergistic response that has also been noted for the MurA-specific antibiotic fosfomycin. These experiments form the basis of mode-ofaction detection assays that can be used in the discovery of novel MetS-or MurB-specific antibiotic drugs that are effective against B. anthracis or other gram-positive bacterial pathogens.

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Selection of Bacillus anthracis isolates resistant to antibiotics

Abstract: The ease with which B. anthracis can be made resistant in vitro suggests that close monitoring of patients treated for anthrax is mandatory.

Cited by 110 publications

References 11 publications

Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

Daptomycin exerts rapid bactericidal activity against Bacillus anthracis without disrupting membrane integrity

PlyPH, a Bacteriolytic Enzyme with a Broad pH Range of Activity and Lytic Action against Bacillus anthracis

Evaluation of the metS and murB Loci for Antibiotic Discovery Using Targeted Antisense RNA Expression Analysis in Bacillus anthracis

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