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Sublethal concentrations of carbapenems alter cell morphology and genomic
expression of Klebsiella pneumoniae biofilms
#MMPMID25583711
Van Laar TA
; Chen T
; You T
; Leung KP
Antimicrob Agents Chemother
2015[Mar]; 59
(3
): 1707-17
PMID25583711
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Klebsiella pneumoniae, a Gram-negative bacterium, is normally associated with
pneumonia in patients with weakened immune systems. However, it is also a
prevalent nosocomial infectious agent that can be found in infected surgical
sites and combat wounds. Many of these clinical strains display multidrug
resistance. We have worked with a clinical strain of K. pneumoniae that was
initially isolated from a wound of an injured soldier. This strain demonstrated
resistance to many commonly used antibiotics but sensitivity to carbapenems. This
isolate was capable of forming biofilms in vitro, contributing to its increased
antibiotic resistance and impaired clearance. We were interested in determining
how sublethal concentrations of carbapenem treatment specifically affect K.
pneumoniae biofilms both in morphology and in genomic expression. Scanning
electron microscopy showed striking morphological differences between untreated
and treated biofilms, including rounding, blebbing, and dimpling of treated
cells. Comparative transcriptome analysis using RNA sequencing (RNA-Seq)
technology identified a large number of open reading frames (ORFs) differentially
regulated in response to carbapenem treatment at 2 and 24 h. ORFs upregulated
with carbapenem treatment included genes involved in resistance, as well as those
coding for antiporters and autoinducers. ORFs downregulated included those coding
for metal transporters, membrane biosynthesis proteins, and motility proteins.
Quantitative real-time PCR validated the general trend of some of these
differentially regulated ORFs. Treatment of K. pneumoniae biofilms with sublethal
concentrations of carbapenems induced a wide range of phenotypic and gene
expression changes. This study reveals some of the mechanisms underlying how
sublethal amounts of carbapenems could affect the overall fitness and pathogenic
potential of K. pneumoniae biofilm cells.
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