Related Experiment Videos
Development of resistance during antimicrobial therapy caused by insertion sequence interruption of porin genes
S Hernández-Allés1, V J Benedí, L Martínez-Martínez
1Departamento de Biología, Universidad de las Islas Baleares, Palma de Mallorca, Spain.
Abstract:
We have demonstrated by using an in vitro approach that interruption of the OmpK36 porin gene by insertion sequences (ISs) is a common type of mutation that causes loss of porin expression and increased resistance to cefoxitin in Klebsiella pneumoniae. This mechanism also operates in vivo: of 13 porin-deficient cefoxitin-resistant clinical isolates of K. pneumoniae, 4 presented ISs in their ompK36 gene.
Insights
Insertion sequences (ISs) commonly disrupt the OmpK36 porin gene in Klebsiella pneumoniae, leading to cefoxitin resistance. This genetic mechanism was observed both in vitro and in vivo clinical isolates.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Klebsiella pneumoniae is an opportunistic pathogen frequently associated with hospital-acquired infections.
- Antibiotic resistance, particularly to beta-lactam antibiotics like cefoxitin, is a growing global health concern.
- Porins, such as OmpK36, play a crucial role in the outer membrane permeability of Gram-negative bacteria, influencing antibiotic susceptibility.
Purpose of the Study:
- To investigate the role of porin gene mutations in cefoxitin resistance in Klebsiella pneumoniae.
- To identify the specific genetic mechanisms underlying the loss of OmpK36 porin expression.
- To determine the prevalence of these mutations in both laboratory and clinical settings.
Main Methods:
- In vitro studies involving genetic manipulation to assess the impact of insertion sequences on OmpK36 expression.
- Analysis of clinical isolates of Klebsiella pneumoniae exhibiting porin deficiency and cefoxitin resistance.
- Molecular techniques to identify and characterize insertion sequences within the ompK36 gene.
Main Results:
- Insertion sequences (ISs) were identified as a frequent cause of OmpK36 porin gene disruption.
- Disruption of the OmpK36 gene by ISs resulted in a loss of porin expression.
- This loss of porin expression correlated with increased resistance to the antibiotic cefoxitin.
- The identified mechanism was validated in vivo, with 4 out of 13 clinical isolates showing ISs in their ompK36 gene.
Conclusions:
- Interruption of the OmpK36 porin gene by insertion sequences is a significant mechanism contributing to cefoxitin resistance in Klebsiella pneumoniae.
- This genetic alteration impacts bacterial virulence and antibiotic treatment outcomes.
- Understanding these resistance mechanisms is vital for developing effective therapeutic strategies against Klebsiella pneumoniae infections.