Development of ciprofloxacin resistance in <i>Brucella melitensis</i>

Al-Sibai, M. Badawi; Qadri, S. M. Hussain

doi:10.1093/jac/25.2.302

Cited by 29 publications

(17 citation statements)

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“…In addition, a lack of effective bactericidal activity of fluoroquinolones against Brucella spp. has often been reported (5,6,30,64,68). In this regard, it should be noted that TolC-dependent efflux processes (Fig.…”

Section: Discussionmentioning

confidence: 75%

The TolC Homologue of Brucella suis Is Involved in Resistance toAntimicrobial Compounds and Virulence

Posadas

Martín

García³

et al. 2007

Infect Immun

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Brucella spp., like other pathogens, must cope with the environment of diverse host niches during the infection process. In doing this, pathogens evolved different type of transport systems to help them survive and disseminate within the host. Members of the TolC family have been shown to be involved in the export of chemically diverse molecules ranging from large protein toxins to small toxic compounds. The role of proteins from the TolC family in Brucella and other ␣-2-proteobacteria has been explored little. The gene encoding the unique member of the TolC family from Brucella suis (BepC) was cloned and expressed in an Escherichia coli mutant disrupted in the gene encoding TolC, which has the peculiarity of being involved in diverse transport functions. BepC fully complemented the resistance to drugs such as chloramphenicol and acriflavine but was incapable of restoring hemolysin secretion in the tolC mutant of E. coli. An insertional mutation in the bepC gene strongly affected the resistance phenotype of B. suis to bile salts and toxic chemicals such as ethidium bromide and rhodamine and significantly decreased the resistance to antibiotics such as erythromycin, ampicillin, tetracycline, and norfloxacin. Moreover, the B. suis bepC mutant was attenuated in the mouse model of infection. Taken together, these results suggest that BepC-dependent efflux processes of toxic compounds contribute to B. suis survival inside the host.Brucella spp. are responsible for a zoonosis that causes a serious economical impact worldwide and a human disease that is difficult to treat (8,16,22). Brucella enters the host via the nasal, oral, and pharyngeal cavities, and after penetrating the mucosal epithelium, the organism is transported to the lymph nodes. During early infection, innate immunity mechanisms from the host contribute to reduce the initial number of infecting Brucella cells (38). Brucella has the ability to invade and survive within macrophages and nonphagocytic cells. After entering the host cell, Brucella is found in a membrane-associated vacuole (phagosome). Brucella subverts the intracellular endocytic pathway, bypassing the classical lysosomal pathway; the bacteria multiplicate and survive in a compartment associated with rough endoplasmic reticulum (for recent reviews, see references 33 and 69). By using this strategy, the bacterium escapes some bactericidal mechanisms (10).The outer membrane of Brucella is considerably hydrophobic compared to those of other ␣-2-proteobacteria and therefore more permeable to lipophilic compounds (54). Conversely, the hydrophobic character of the outer membrane makes Brucella relatively resistant to polycationic peptides. In other species, low permeability to hydrophobic compounds goes together with efflux systems to increase protection against toxic molecules (47). Therefore, this unusual characteristic of the outer membrane raises interesting questions about the physiology of Brucella spp. Some outer membrane proteins (76) and the O side chain component of the lipopolysaccharid...

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Section: Discussionmentioning

confidence: 75%

The TolC Homologue of Brucella suis Is Involved in Resistance toAntimicrobial Compounds and Virulence

Posadas

Martín

García³

et al. 2007

Infect Immun

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“…All the 104 isolates of B. melitensis shown in Table 1 responded in vitro to 0.5-2.0 mg/L of CI-990. One of the isolates from a patient with acute discitis developed resistance to ciprofloxacin with an MIC of >4.0 mg/L, while under treatment with this drug [12][13][14]. The parent strain was susceptible to ciprofloxacin, CI-990 and other fluoroquinolones with an MIC of 0.06-2.0 mg/L.…”

Section: Resultsmentioning

confidence: 99%

CI-990 (PD 131112): A New Quinolone Prodrug

Ueno

Saldin

et al. 1993

Ann Saudi Med

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In vitro susceptibility of 1021 strains of recent clinical isolates was determined against the new fluoroquionolone CI-990 (PD 131112) and compared with CI-960, ciprofloxacin, fleroxacin, lomefloxacin, norfloxacin, pefloxacin. sparfloxacin. and temafloxacin. The minimum inhibitory concentrations (MIC) of CI-990 in mg/L required for >90% isolates were 0.03-0.5 for members of Enterobacteriaceae, 0.12-2.0 for Pseudomonas aeruginosa, 0.03-1.0 for Aeromonas hydrophila, 1.0-2.0 for Acinetobacter calcoaceticus, 0.5-2.0 for Brucella melitensis, 0.06-1.0 for staphylococci, and 1.0-2.0 for enterococci. Its antibacterial activity was comparable or superior to other fluoroquinolones tested against most gram-negative and grampositive bacteria, including enterococci.

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“…However, resistance to the fluoroquinolones has been found following therapy of infections caused by P. aeruginosa, S. aureus, and B. melitensis [3,19,20]. It remains to be seen whether widespread use will lead to a significant increase in resistance.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity of Fluoroquinolones Local Clinical Isolates from a Referral Center in Riyadh

1992

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A total of 1,034 clinical isolates from a tertiary care center were tested against six fluoroquinolones, namely norfloxacin, ciprofloxacin, lomefloxacin, sparfloxacin, temafloxacin, and CI-960. Bacteria tested consisted of 579 strains of Enterobacteriaceae, 98 pseudomonads, 51 Acinetebacter, 56 enterococci and 250 isolates of staphylococci. All six fluoroquinolones showed excellent in vitro activity inhibiting >90% of Escherichia coli at an MIC of < 0.03-0.5 mg/L, Klebsiella pneumoniae at 0.12-2.0 mg/L, Enterobacter at 0.12-2.0 mg/L, Serratia marcescens at 0.12-2.0 mg/L, Pseudomonas aeruginosa at 0.5-2.0 mg/L, Staphylococus aureus at < 0.03-1.0 mg/L, and coagulase negative staphylococci at an MIC of 0.12-2.0 mg/L Xanthomonas maltophilia showed some resistance to norfloxacin, ciprofloxacin, lomefloxacin and temafloxacin, but was inhibited by sparfloxacin and CI-960. A majority of isolates of enterococci were resistant to norfloxacin, ciprofloxacin, lomefloxacin and CI-960, but sparfloxacin and temafloxacin inhibited 92% and 82% of these strains, respectively. The newer fluoroquinolones are a major advance in antimicrobial chemotherapy and have evolved from chemical modifications of nalidixic acid [1]. The first breakthrough occurred during the early 1980s when norfloxacin, a second generation quinolone with 6-flourine and 7-piperazine substituents, was synthesized. The enhanced activity of this drug as an orally active agent for urinary tract infections resulted in further development of other fluoroquinolones such as ciprofloxacin and later by third generation quinolones such as lomefloxacin, sparfloxacin, temafloxacin, and CI-960 [2]. The newer 4-quinolone antibacterial agents possess a carboxyl group at position four. The addition of a piperazine at position seven confers increased antimicrobial activity, especially against P. aeruginosa. Fluorination of the nucleus at position six increases antibacterial potency. In fact, the trend in the synthesis of newer third generation agents has been to increase the number of flourine residues. Structural changes of the parent compound (Figure 1) have thus resulted in extended spectrum of activity, better penetration, and improved pharmacokinetic properties.

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Development of ciprofloxacin resistance in Brucella melitensis

Cited by 29 publications

References 0 publications

The TolC Homologue of Brucella suis Is Involved in Resistance toAntimicrobial Compounds and Virulence

The TolC Homologue of Brucella suis Is Involved in Resistance toAntimicrobial Compounds and Virulence

CI-990 (PD 131112): A New Quinolone Prodrug

Antibacterial Activity of Fluoroquinolones Local Clinical Isolates from a Referral Center in Riyadh

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