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Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Found Persisting Silently in Infant Gut Microbiota
I Y Vasilyev1, I V Nikolaeva2, M N Siniagina1
1Institute of Fundamental Medicine and Biology, Federal University, 420008 Ulitsa Kremlyovskaya 18, Kazan, Russia.
Abstract:
Since the spread of multidrug-resistant Klebsiella pneumoniae (MDRKP) strains is considered as a challenge for patients with weakened or suppressed immunity, the emergence of isolates carrying determinants of hypervirulent phenotypes in addition may become a serious problem even for healthy individuals. The aim of this study is an investigation of the nonoutbreak K. pneumoniae emergence occurred in early 2017 at a maternity hospital of Kazan, Russia. Ten bacterial isolates demonstrating multiple drug resistance phenotypes were collected from eight healthy full-term breastfed neonates, observed at the maternity hospital of Kazan, Russia. All the infants and their mothers were dismissed without symptoms or complaints, in a satisfactory condition. Whole-genome shotgun (WGS) sequencing was performed with the purpose to track down a possible spread source(s) and obtain detailed information about resistance determinants and pathogenic potential of the collected isolates. Microdilution tests have confirmed production of extended-spectrum β-lactamases (ESBL) and their resistance to aminoglycoside, β-lactam, fluoroquinolone, sulfonamide, nitrofurantoin, trimethoprim, and fosfomycin antibiotics and Klebsiella phage. The WGS analysis has revealed the genes that are resistant to aminoglycosides, fluoroquinolones, macrolides, sulfonamides, chloramphenicols, tetracyclines, and trimethoprim and ESBL determinants. The pangenome analysis had split the isolates into two phylogenetic clades. The first group, a more heterogeneous clade, was represented by 5 isolates with 4 different in silico multilocus sequence types (MLSTs). The second group contained 5 isolates from infants born vaginally with the single MLST ST23, positive for genes corresponding to hypervirulent phenotypes: yersiniabactin, aerobactin, salmochelin, colibactin, hypermucoid determinants, and specific alleles of K- and O-antigens. The source of the MDRKP spread was not defined. Infected infants have shown no developed disease symptoms.
Insights
Multidrug-resistant Klebsiella pneumoniae (MDRKP) strains were found in healthy neonates. Some isolates possessed hypervirulent genes, posing a potential risk even to healthy individuals, though the source remains unknown.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Multidrug-resistant Klebsiella pneumoniae (MDRKP) poses a significant threat, particularly to immunocompromised individuals.
- The emergence of hypervirulent MDRKP strains presents a novel challenge, potentially affecting even healthy populations.
- Understanding the genetic basis and transmission dynamics of MDRKP is crucial for public health.
Purpose of the Study:
- To investigate the emergence of nonoutbreak MDRKP isolates in healthy neonates at a maternity hospital in Kazan, Russia.
- To characterize the antimicrobial resistance determinants and pathogenic potential of these isolates using whole-genome sequencing.
- To identify the phylogenetic relationships and potential sources of MDRKP transmission within the hospital setting.
Main Methods:
- Collection and phenotypic characterization of ten MDRKP isolates from eight healthy neonates.
- Antimicrobial susceptibility testing including microdilution assays.
- Whole-genome shotgun (WGS) sequencing for comprehensive genetic analysis.
- Pangenome analysis and in silico multilocus sequence typing (MLST) for phylogenetic classification.
Main Results:
- All ten isolates exhibited multidrug resistance, including resistance to extended-spectrum beta-lactamases (ESBLs) and various antibiotic classes.
- WGS identified genes conferring resistance to aminoglycosides, fluoroquinolones, macrolides, sulfonamides, chloramphenicols, tetracyclines, and trimethoprim.
- Pangenome analysis revealed two distinct phylogenetic clades; one clade (ST23) carried genes associated with hypervirulence (yersiniabactin, aerobactin, salmochelin, colibactin, hypermucoid factors, specific K- and O-antigens).
- The source of the MDRKP spread could not be determined, and infected infants remained asymptomatic.
Conclusions:
- The study identified MDRKP strains with hypervirulent potential in healthy neonates, highlighting a potential emerging public health concern.
- Despite the presence of virulence factors, the infected infants showed no clinical signs of disease.
- Further investigation is needed to elucidate the transmission dynamics and clinical implications of hypervirulent MDRKP in neonatal populations.
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