Reduced Virulence and Enhanced Host Adaption during Antibiotics Therapy: a Story of a Within-Host Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Evolution in a Patient with a Serious Scrotal Abscess

Ye, Meiping; Liao, Chunjie; Shang, Mengya; Zou, Danyang; Feng, Xin; Lu, Xing; Zhang, Yixin; Yan, Jingmin; Hu, Zhixiang; Xu, Xiaogang; Jiang, Jianping; Zhou, Pingyu

doi:10.1128/msystems.01342-21

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…Further analyses, including gene knockout and phenotypic tests, indicated that the ntrd morphotype was caused by capsule deficiency mediated by point mutations, or disruption of the cps genes by diverse ISs (include ISKpn74 and ISKpn26). A recent study by Ye et al also indicated that deletion of the acyltransferase gene ( act ) from the cps locus plays a crucial role in the evolution of virulence of ST11 CRKP [ 38 ]. The capsule is a critical virulence factor, and was shown to be costly in nutrient-rich media in a study by Buffet et al [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae

Chen,

Wang,

Chi

et al. 2024

Virulence

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ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the “mcsw” morphotype. Two distinct morphotypes (“ntrd” and “msdw”) were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis ( wza , wzc , and wbaP ), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.

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Section: Discussionmentioning

confidence: 99%

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae

Chen,

Wang,

Chi

et al. 2024

Virulence

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“…Such microdiversity is a result of either repetitive infections or in vivo diversifying evolution of a single clone during prolonged infections, and it could be clinically important when different strains have different AMR susceptibilities. For example, ST11-KPC-2 isolates have been reported to gain additional resistance to ceftazidime-avibactam and tigecycline by mutations in D179Y and the ramR gene during long-term treatments ( 20 , 38 ). Here, we compared genomic sequences of 19 sets of CRKPs that were each isolated from the same patients.…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis Revealed the International and Domestic Transmission of Carbapenem-Resistant Klebsiella pneumoniae in Chinese Pediatric Patients

Jiang

Liu

et al. 2023

Microbiol Spectr

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Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in pediatric patients differs from that in adults patients in terms of both genetic and phenotypic features, which remain to be elucidated. We present a summary of prevalent CRKP isolates from Chinese pediatric patients over 8 years, demonstrating the prevalence and clinical importance of New Delhi metallo-β-lactamase genes in pediatric patients, mainly describing the genomic features of two predominant CRKP clones (ST11 and ST14) in Chinese children, and identifying four carbapenemase-encoding plasmids that contribute to the transmission of most carbapenemase genes in hospitals.

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“…One of the potential reasons for this may be stated as increased AMR and prolonged antimicrobial exposure, which come with a fitness cost to bacteria such as reduced virulence and altered pathogenesis [38,39]. In previously published studies, it has been observed that A. baumannii has diminished its biofilm formation ability, in vivo dissemination, and surface motility upon conferring colistin resistance [40,41].…”

Section: Discussionmentioning

confidence: 99%

Does Emerging Carbapenem Resistance in Acinetobacter baumannii Increase the Case Fatality Rate? Systematic Review and Meta-Analysis

Boral,

Pınarlık,

Ekinci

et al. 2023

Infectious Disease Reports

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Background: In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. Methods: Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. Results: A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). Conclusions: Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate.

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Reduced Virulence and Enhanced Host Adaption during Antibiotics Therapy: a Story of a Within-Host Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Evolution in a Patient with a Serious Scrotal Abscess

Cited by 9 publications

References 43 publications

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae

Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant Klebsiella pneumoniae

Genomic Analysis Revealed the International and Domestic Transmission of Carbapenem-Resistant Klebsiella pneumoniae in Chinese Pediatric Patients

Does Emerging Carbapenem Resistance in Acinetobacter baumannii Increase the Case Fatality Rate? Systematic Review and Meta-Analysis

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