A bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis

Biswas, Sanket; Raoult, Didier; Rolain, Jean‐Marc

doi:10.1016/j.ijantimicag.2008.03.017

Cited by 68 publications

(60 citation statements)

References 132 publications

(158 reference statements)

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“…Thus, looking at in vitro and in silico results, it was found that O. tsutsugamushi strain Kato was intrinsically resistant to ciprofloxacin and that all available sequences of the O. tsutsugamushi QRDR domain of gyrA had an intrinsic mutation at position 83 known to be associated with fluoroquinolone resistance, as has been established in other intracellular bacteria including Ehrlichia spp., Bartonella spp. and Tropheryma whipplei [11,12]. Therefore, these data provide evidence that O. tsutsugamushi is naturally resistant to fluoroquinolones, explaining clinical failures reported using such antibiotics in the treatment of scrub typhus.…”

Section: Resultsmentioning

confidence: 73%

“…Fluoroquinolone activity is due to inhibition of bacterial DNA gyrase (topoisomerase II) and topoisomerase IV. It has been demonstrated that resistance to quinolones in intracellular bacteria was mainly due to point mutations in the quinolone resistance-determining region (QRDR) of DNA gyrase (gyrA) [11,12]. Surprisingly, there are only a few reports regarding in vitro and/or in vivo antibiotic susceptibility in cell culture or animal models of O. tsutsugamushi, especially for fluoroquinolones.…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Tantibhedhyangkul

Angelakis

Tongyoo

et al. 2010

International Journal of Antimicrobial Agents

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Scrub typhus is a public health concern for a population of over a billion humans, with an estimated incidence of one million cases/year in endemic areas. Although doxycycline remains the standard therapy, fluoroquinolones have been used successfully in a few patients. However, there is also clinical evidence that fluoroquinolones are ineffective in the treatment of scrub typhus. To clarify this matter, we determined the in vitro susceptibility of Orientia tsutsugamushi strain Kato to ciprofloxacin and sequenced the quinolone resistance-determining region (QRDR) of the gyrA gene, the target of fluoroquinolones, of 18 fresh isolates from Lao PDR.Orientia tsutsugamushi strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum inhibitory concentration = 8 g/mL). All sequences obtained, including those from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda), had a Ser83Leu mutation in their QRDR domain that is known to be associated with fluoroquinolone resistance. These findings re-emphasise the usefulness of in silico analysis for the prediction of antibiotic resistance and suggest that fluoroquinolones should not be used in the treatment of scrub typhus.

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Section: Resultsmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Tantibhedhyangkul

Angelakis

Tongyoo

et al. 2010

International Journal of Antimicrobial Agents

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“…Conversely, clinical data indicate that the bacteria may be more resistant in vivo. For Bartonella, in which potential mechanisms of drug efflux are not known, the other antibiotic resistance systems such as tetracycline resistance protein and macrolide-specific efflux proteins were identified by in silico genome analysis of Bartonella (Biswas et al, 2008), suggesting that some drug resistance systems including BH10650 may play an important role in vivo or in overexpressions.…”

Section: Discussionmentioning

confidence: 99%

Proteomic and bioinformatic analysis of outer membrane proteins of the protobacterium Bartonella henselae (Bartonellaceae)

Dm¹,

Qy²,

Zhao³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Bartonella henselae, an infectious agent causing catscratch disease and vasculoproliferative disorders in humans, is a fastidious facultative intracellular pathogen. The outer membrane proteins of B. henselae are key molecules that play a primary role in host-cell interactions. We isolated B. henselae outer membrane proteins, using the ionic detergent N-lauroyl sarcosine sodium salt and sodium carbonate, purification by two-dimensional (2-D) gel electrophoresis, and protein identification using mass spectrometry. Treatment with buffers containing ASB-14 and ZWITTERGENT 3-10 increased solubilization of B. henselae proteins, particularly proteins with basic pI. Three hundred and sixty- eight spots were detected from the sarcosine-insoluble outer membrane fraction; 94 distinct protein species were identified from 176 spots. In the outer membrane fraction from carbonate incubation, 471 spots were calculated and 259 spots were identified, which included 139 protein entries. There were six outer membrane proteins in the sarcosine-insoluble outer membrane fraction compared with nine outer membrane proteins from samples subjected to carbonate incubation. We used bioinformatic analysis to identify 44 outer membrane proteins by prediction of their domains and tertiary structures and documented the potential virulence factors. We established the 2-D reference maps of the outer membrane subproteome of B. henselae using the two different extraction methods, which were partly complementary to each other. Sodium carbonate extraction isolated low-abundance and basic proteins better than the lauroyl sarcosine sodium salt extraction, which enriched high-abundance porins.

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“…Being an obligate intracellular parasite, its 2 forms EBs and RBs develop diverse strategies to survive within this compartment. The barrier to its antibiotic treatment is the difference between the localization of antibiotics within the cellular compartment of infected cells and the localization of bacteria; hence, antibiotics need to reach and concentrate within intracellular compartments [30][31][32] . Azithromycin is known to have a high penetration and accumulation capacity intracellularly as compared to other antibiotics found to be more effective against intracellular pathogens [33] .…”

Section: Discussionmentioning

confidence: 99%

Decreased Susceptibility to Azithromycin and Doxycycline in Clinical Isolates of<i> Chlamydia trachomatis</i> Obtained from Recurrently Infected Female Patients in India

et al. 2010

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Background: Recurrent genital Chlamydia trachomatis infection often results in serious sequelae and has a major impact on reproductive health. Materials and Methods: Recurrent infections were determined in symptomatic female patients. In vitro susceptibility assay was performed for azithromycin and doxycycline using the cell culture technique against 21 clinical isolates obtained from C. trachomatis-positive patients including those who were recurrently infected. Results: Thirteen isolates (61.9%) were found to be susceptible to azithromycin and doxycycline with minimum inhibitory concentration (MIC) values ≤0.125 and ≤0.25 µg/ml, respectively. Eight isolates (38%) were found to be less susceptible to the drugs. Two of them had MICs of 8 µg/ml for both the drugs and could not be completely eradicated as observed by minimum bactericidal concentration assay. Conclusions: Decreased antibiotic susceptibility to the current first-line drugs (azithromycin and doxycycline) for chlamydial infection treatment was observed in isolates obtained from recurrently infected patients.

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A bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis

Cited by 68 publications

References 132 publications

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi

Proteomic and bioinformatic analysis of outer membrane proteins of the protobacterium Bartonella henselae (Bartonellaceae)

Decreased Susceptibility to Azithromycin and Doxycycline in Clinical Isolates of<i> Chlamydia trachomatis</i> Obtained from Recurrently Infected Female Patients in India

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