Analysis of a novel class A β-lactamase OKP-B-6 of Klebsiella quasipneumoniae: structural characterisation and interaction with commercially available drugs
Mem. Inst. Oswaldo Cruz
;
117: e220102, 2022. tab, graf
Article
in English
|
LILACS-Express
| LILACS
| ID: biblio-1405992
ABSTRACT
BACKGROUND Gram-negative and Gram-positive bacteria produce beta-lactamase as factors to overcome beta-lactam antibiotics, causing their hydrolysis and impaired antimicrobial action. Class A beta-lactamase contains the chromosomal sulfhydryl reagent variable (SHV, point mutation variants of SHV-1), LEN (Klebsiella pneumoniae strain LEN-1), and other K. pneumoniae beta-lactamase (OKP) found mostly in Klebsiella's phylogroups. The SHV known as extended-spectrum β-lactamase can inactivate most beta-lactam antibiotics. Class A also includes the worrisome plasmid-encoded Klebsiella pneumoniae carbapenemase (KPC-2), a carbapenemase that can inactivate most beta-lactam antibiotics, carbapenems, and some beta-lactamase inhibitors. OBJECTIVES So far, there is no 3D crystal structure for OKP-B, so our goal was to perform structural characterisation and molecular docking studies of this new enzyme. METHODS We applied a homology modelling method to build the OKP-B-6 structure, which was compared with SHV-1 and KPC-2 according to their electrostatic potentials at the active site. Using the DockThor-VS, we performed molecular docking of the SHV-1 inhibitors commercially available as sulbactam, tazobactam, and avibactam against the constructed model of OKP-B-6. FINDINGS From the point of view of enzyme inhibition, our results indicate that OKP-B-6 should be an extended-spectrum beta-lactamase (ESBL) susceptible to the same drugs as SHV-1. MAIN CONCLUSIONS This conclusion advantageously impacts the clinical control of the bacterial pathogens encoding OKP-B in their genome by using any effective, broad-spectrum, and multitarget inhibitor against SHV-containing bacteria.
Full text:
Available
Index:
LILACS (Americas)
Type of study:
Prognostic study
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2022
Type:
Article
/
Project document
Affiliation country:
Brazil
Institution/Affiliation country:
Laboratório Nacional de Computação Científica/BR
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