Appearance of Macrolide-Resistant Bordetella pertussis Strains in China

Wang, Zengguo; Li, Yarong; Hou, Tiejun; Liu, Xiaoguai; Liu, Ying; Yu, Tianzhi; Chen, Zhijun; Gao, Yuan; Li, Hengxin; He, Qiushui

doi:10.1128/aac.01081-13

Cited by 38 publications

(42 citation statements)

References 7 publications

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“…Macrolide-resistant B. pertussis has been isolated in the USA, China and, for the first time in the year 2012, in Europe [27][28][29]. The erythromycin-resistant B. pertussis isolated is mutated in a region critical for erythromycin binding, an A to G transition at nucleotide position 2047 of the 23S rRNA gene [27][28][29].…”

Section: Macrolide Resistancementioning

confidence: 99%

“…The erythromycin-resistant B. pertussis isolated is mutated in a region critical for erythromycin binding, an A to G transition at nucleotide position 2047 of the 23S rRNA gene [27][28][29]. As macrolide resistance is rare, antimicrobial susceptibility testing is not routinely recommended; however, it is indicated in case of suspected treatment failure [12].…”

Section: Macrolide Resistancementioning

confidence: 99%

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Management and prevention of pertussis infection in neonates

Berti

Venturini

Galli

et al. 2014

Expert Review of Anti-infective Therapy

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Despite the fact that universal immunization against pertussis led to a dramatic decrease in the incidence and mortality in high-income countries, it has left a window of vulnerability for newborns. Although specific guidelines concerning management of neonatal whooping cough have not yet been developed, the present review summarizes the main available recommendations on diagnostic work-up and treatment of neonatal pertussis. Additionally, new prevention strategies are explored, including the use of an additional booster dose of vaccine to adolescents and adults, vaccination of healthcare workers, immunization of household contacts and caregivers (cocooning strategy), vaccination of pregnant women and, finally, neonatal immunization with novel vaccines. These strategies are analyzed and discussed in terms of efficacy, safety and cost-effectiveness.

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Section: Macrolide Resistancementioning

confidence: 99%

Section: Macrolide Resistancementioning

confidence: 99%

Management and prevention of pertussis infection in neonates

Berti

Venturini

Galli

et al. 2014

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

show abstract

“…from USA 3 , indicate that the number of cases is increasing. Moreover, macrolide resistant B. pertussis strains have been reported 4, 5 . Sizeable outbreaks have also been witnessed 1 , but the reasons for the resurgence are incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

Discovery of compounds inhibiting the ADP-ribosyltransferase activity of pertussis toxin

Ashok

Miettinen

Oliveira

et al. 2019

Preprint

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Targeted pathogen-selective approach to antibiotic development holds promise to minimize collateral damage to the beneficial microbiome. The AB5-topology pertussis toxin (PtxS1-S5, 1:1:1:2:1) is a major virulence factor of Bordetella pertussis, the causative agent of the highly contagious respiratory disease whooping cough. Once internalized into the host cell, PtxS1 ADP-ribosylates α-subunits of the heterotrimeric Gαi-superfamily, thereby disrupting G-protein-coupled receptor signaling. Here, we report the discovery of the first small molecules inhibiting the ADP-ribosyltransferase activity of pertussis toxin. We developed protocols to purify mg-levels of truncated but highly active recombinant B. pertussis PtxS1 from Escherichia coli and an in vitro high throughput-compatible assay to quantify NAD+ consumption during PtxS1-catalyzed ADP-ribosylation of Gαi. Two inhibitory compounds (NSC228155 and NSC29193) with low micromolar IC50-values (3.0 µM and 6.8 µM) were identified in the in vitro NAD+ consumption assay that also were potent in an independent in vitro assay monitoring conjugation of ADP-ribose to Gαi. Docking and molecular dynamics simulations identified plausible binding poses of NSC228155 and in particular of NSC29193, most likely owing to the rigidity of the latter ligand, at the NAD+-binding pocket of PtxS1. NSC228155 inhibited the pertussis AB5 holotoxin-catalyzed ADP-ribosylation of Gαi in living human cells with a low micromolar IC50-value (2.4 µM). NSC228155 and NSC29193 might prove useful hit compounds in targeted B. pertussis-selective drug development.

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“…The first erythromycin-resistant Bordetella pertussis was discovered in 1994 (2). Although resistant strains are still rare, they have been reported in several countries, including China (3)(4)(5)(6)(7), where macrolide-resistant B. pertussis has become prevalent (7).…”

mentioning

confidence: 99%

“…Several studies have proven the association between macrolide resistance and the A2047G mutation in the 23S rRNA of B. pertussis (3)(4)(5)(6)(7). Based on the molecular mechanism identified, methods have been developed for detection of the point mutation in 23S rRNA of B. pertussis in order to study the susceptibility to macrolides when B. pertussis isolates are available (3,5).…”

mentioning

confidence: 99%

Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical Specimens by PCR

et al. 2015

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Resistance of Bordetella pertussis to erythromycin has been increasingly reported. We developed an allele-specific PCR method for rapid detection of erythromycin-resistant B. pertussis directly from nasopharyngeal (NP) swab samples submitted for diagnostic PCR. Based on the proven association of erythromycin resistance with the A2047G mutation in the 23S rRNA of B. pertussis, four primers, two of which were designed to be specific for either the wild-type or the mutant allele, were used in two different versions of the allele-specific PCR assay. The methods were verified with results obtained by PCR-based sequencing of 16 recent B. pertussis isolates and 100 NP swab samples submitted for diagnostic PCR. The detection limits of the two PCR assays ranged from 10 to 100 fg per reaction for both erythromycin-susceptible and -resistant B. pertussis. Two amplified fragments of each PCR, of 286 and 112 bp, respectively, were obtained from a mutant allele of the isolates and/or NP swab samples containing B. pertussis DNAs. For the wild-type allele, only a 286-bp fragment was visible when the allele-specific PCR assay 1 was performed. No amplification was found when a number of non-Bordetella bacterial pathogens and NP swab samples that did not contain the DNAs of B. pertussis were examined. This assay can serve as an alternative for PCR-based sequencing, especially for local laboratories in resource-poor countries. P ertussis has resurged in many countries. Macrolides, especially erythromycin, are considered the first-choice antibiotics for treatment of pertussis and postexposure prophylaxis (1). The first erythromycin-resistant Bordetella pertussis was discovered in 1994 (2). Although resistant strains are still rare, they have been reported in several countries, including China (3-7), where macrolide-resistant B. pertussis has become prevalent (7).B. pertussis is a fastidious bacterium. The culture positivity rate is low in immunized populations. The PCR method has been developed and used for diagnosis of pertussis in many laboratories all over the world. However, it is possible that resistant B. pertussis strains are missed due to failure of the culture and when culture is not performed (8).Several studies have proven the association between macrolide resistance and the A2047G mutation in the 23S rRNA of B. pertussis (3-7). Based on the molecular mechanism identified, methods have been developed for detection of the point mutation in 23S rRNA of B. pertussis in order to study the susceptibility to macrolides when B. pertussis isolates are available (3, 5). In a previous study, we developed a PCR-based sequencing method for identification of the A2047G mutation in cultured B. pertussis isolates and clinical nasopharyngeal (NP) specimens (7).Although the sequencing is widely used, it is not available or accessible everywhere because it takes longer to obtain the results in many of the local laboratories, especially in resource-poor countries. In this study, we aimed to develop a simple allele-specific PCR method for di...

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Appearance of Macrolide-Resistant Bordetella pertussis Strains in China

Cited by 38 publications

References 7 publications

Management and prevention of pertussis infection in neonates

Management and prevention of pertussis infection in neonates

Discovery of compounds inhibiting the ADP-ribosyltransferase activity of pertussis toxin

Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical Specimens by PCR

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