Ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae accompanied hypermucoviscosity acquisition.
Klebsiella pneumoniae
/ genetics
Ceftazidime
/ pharmacology
Azabicyclo Compounds
/ pharmacology
Drug Combinations
beta-Lactamases
/ genetics
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ genetics
Humans
Klebsiella Infections
/ microbiology
Microbial Sensitivity Tests
Drug Resistance, Multiple, Bacterial
/ genetics
K. pneumoniae
wzc
Ceftazidime-avibactam resistance
Hypermucoviscosity
KPC
Journal
BMC microbiology
ISSN: 1471-2180
Titre abrégé: BMC Microbiol
Pays: England
ID NLM: 100966981
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
26
03
2024
accepted:
09
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp). The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI. These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process.
Sections du résumé
BACKGROUND
BACKGROUND
Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp).
RESULTS
RESULTS
The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI.
CONCLUSIONS
CONCLUSIONS
These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process.
Identifiants
pubmed: 39468460
doi: 10.1186/s12866-024-03508-w
pii: 10.1186/s12866-024-03508-w
doi:
Substances chimiques
Ceftazidime
9M416Z9QNR
Azabicyclo Compounds
0
avibactam, ceftazidime drug combination
0
Drug Combinations
0
beta-Lactamases
EC 3.5.2.6
Anti-Bacterial Agents
0
Bacterial Proteins
0
carbapenemase
EC 3.5.2.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
439Subventions
Organisme : Special Foundation for National Science and Technology Basic Research Program of China
ID : 2019FY101200
Organisme : National Natural Science Foundation of China
ID : 81861138056
Informations de copyright
© 2024. The Author(s).
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