A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China

Abstract

BackgroundPrevious limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.MethodsThe present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.ResultsA total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2–9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips.ConclusionThe present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.

Macrolide Resistance in Bordetella pertussis: Current Situation and Future Challenges

“…However, the method was only performed with extracted DNA from cultured B. pertussis , and its usability among DNA extracted from NP samples needs further evaluation. In general, the above-described methods are currently widely used, especially in China, where most of the macrolide-resistant B. pertussis isolates have appeared [ 28 , 40 , 53 ].…”

“…Until recently, macrolide resistance in B. pertussis in China has been associated almost exclusively with the ptxP1 lineage of the bacterium [ 22 , 27 , 29 , 30 , 31 , 32 , 37 ]. However, a recent cross-sectional study describes two ptxP3 isolates from eastern China that had acquired the A2047G mutation in their 23S rRNA gene [ 40 ]. The ptxP3 lineage is currently the dominating B. pertussis circulating in most of the high-income countries that have switched to acellular pertussis vaccine in recent decades [ 51 , 52 ].…”

“…The emergence of macrolide resistance has raised new questions regarding the optimal treatment of young infants with infection caused by macrolide-resistant B. pertussis . In vitro, several classes of antibiotics seem to be effective against B. pertussis , including SMZ-TMP, levofloxacin, ampicillin, 3rd-generation cephalosporins, gentamicin and piperacillin-tazobactam [ 17 , 34 , 38 , 40 , 46 , 63 ]. However, no data regarding clinical benefit of these antibiotics in infants with severe pertussis caused by a macrolide-resistant strain exist.…”

Pertussis upsurge, age shift and vaccine escape post-COVID-19 caused byptxP3macrolide-resistantBordetella pertussisMT28 clone in China: a genomic epidemiology study

“…18 The circulating B. pertussis stains and pertussis epidemiology in China differ significantly from those in other countries. ptxP1 strains have been predominant in China until 2019, [19][20][21] rather than globally prevalent ptxP3 strains. Moreover, the incidence of MRBP in China is notably high, accounting for over 50% and even 90% of strains in various regions, [21][22][23][24] while MRBP remains rare in other countries.…”

Bordetella spp. utilize the type 3 secretion system to manipulate the VIP/VPAC2 signaling and promote colonization and persistence of the three classical Bordetella in the lower respiratory tract

“…Macrolides are the most common antibiotic given to patients infected with Bordetella spp. However, in Asia, antibiotic resistance is emerging, posing a risk of worldwide dissemination ( Feng et al., 2021 ; Wu et al., 2022 ). Current research focuses on immunotherapies that prevent pathology associated with disease.…”