Download Diversity of mutations of oprD in clinical isolates of carbapenem

Diversity of mutations of oprD in clinical isolates of
carbapenem-resistant Pseudomonas aeruginosa
Date: 2012/5/25
Speaker: Chen-Chi Tsai
Advisor: Min-Jen Tseng
Gram-negative
is
Abstract
Pseudomonas
aeruginosa,
immunocompromised patients.
a
bacterium
an
opportunistic
pathogen
for
Carbapenem is a kind of the -lactam antibiotics against P. aeruginosa.
OprD porin, a specific porin protein, functions as a channel for passive uptake of positively charged
amino acids such as lysine and glutamate across the outer membrane.
resistance of P. aeruginosa to carbapenem antibiotics.
Loss of OprD porin may confer
In this study, a total of 21 strains of clinical
carbapenem-resistant P. aeruginosa (CRPA) were isolated from a regional hospital.
We cloned and
sequenced 16S rDNA of all strains to confirm they indeed be the species of Pseudomonas aeruginosa and
used restriction fragment length polymorphisms (RFLP) to analyze their clonal relatedness.
The
bacterial membrane fractions of a standard ATCC27853 and three clinical strains were extracted and
SDS-PAGE showed these clinical strains lacked the OprD porins as compared to the standard strain.
The oprD of all strains were cloned and sequenced, the clinical isolates showed diverse mutations,
including premature termination of translation caused by single base mutations, deletions and insertions, a
5 base pairs deletion that shifts the translation frame to get a larger but mutant protein, and a large
insertion element (IS) inserts into the beginning of open reading frame.
In conclusion, the diversity of
oprD mutations contributes to the disappearance of OprD porin in the outer membrane of clinical isolates
of CRPA.
Recent reports suggested all classes of bactericidal antibiotics, including carbapenems, promote the
generation of lethal hydroxyl radicals in both Gram-negative and Gram-positive bacteria.
Lethal
hydroxyl radicals can cause DNA damage which induced SOS-related expression of error-prone
polymerase.
In the future work, we like to study whether the mutations of oprD are the outcome of
antibiotics-induced SOS response.
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Diversity of mutations of oprD in clinical isolates of carbapenem-resistant Pseudomonas
aeruginosa
Date: 2012/05/25
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Speaker: Chen-Chi Tsai
Advisor: Min-Jen Tseng
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