Abstract
Pseudomonas aeruginosa is the most common Gram-negative pathogen causing nosocomial multidrug resistant infections. It is a good biofilm producer and has the potential for contaminating medical devices. Despite the widespread use of antibacterial-impregnated catheters, little is known about the impacts of antibacterial coating on the pathogenesis of P. aeruginosa. In this study, we investigated the adaptive resistance potential of P. aeruginosa strain PAO1 in response to continuous antibiotic exposure from clindamycin/rifampicin-impregnated catheters (CR-IC). During exposure for 144 h to clindamycin and rifampicin released from CR-IC, strain PAO1 formed biofilms featuring elongated and swollen cells. There were 545 and 372 differentially expressed proteins (DEPs) identified in the planktonic and biofilm cells, respectively, by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Both Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the planktonic cells responded to the released antibiotics more actively than the biofilm cells, with metabolism and ribosomal biosynthesis-associated proteins being significantly over-expressed. Exposure to CR-IC increased the invasion capability of P. aeruginosa for Hela cells and upregulated the expression of certain groups of virulence proteins in both planktonic and biofilm cells, including the outer membrane associated (flagella, type IV pili and type III secretion system) and extracellular (pyoverdine) virulence proteins. Continuous exposure of P. aeruginosa to CR-IC also induced the overexpression of antibiotic resistance proteins, including porins, efflux pumps, translation and transcription proteins. However, these upregulations did not change phenotypic minimum inhibitory concentration (MIC) during the experimental timeframe. The concerning association between CR-IC and overexpression of virulence factors in P. aeruginosa suggests the need for additional investigation to determine if it results in adverse clinical outcomes.
Highlights
Licensee MDPI, Basel, Switzerland.More than 30 million urinary tract catheters and five million central venous catheters are annually used in the US [1]
We investigated the response of P. aeruginosa PAO1 to the antibiotics eluted from clindamycin/rifampicin-impregnated catheters (CR-IC) by using genetic, minimum inhibitory concentration (MIC) and proteomic analyses to evaluate the potential development of adaptive-resistance and cross-resistance
P. aeruginosa PAO1 survived well when it was grown with CR-IC in the continuous culture but S. aureus strains ATCC 25923 and ATCC BAA-1717 did not
Summary
Licensee MDPI, Basel, Switzerland.More than 30 million urinary tract catheters and five million central venous catheters are annually used in the US [1]. Medical devices are widely used for therapeutic treatments, infections associated with the presence of a device result in significant morbidity and mortality for patients [2]. Nosocomial bacteria can contaminate the surgical site surrounding implants and adhere to their surface to form biofilm, resulting in the evasion of the host immune response and strong resistance to many antimicrobials [3]. Antibacterial therapy is discontinued, persister cells can detach from the biofilm and cause recurrent infections [4]. Host factors and material surface characteristics influence biofilm formation [5,6]. Biofilm can prevent devices from functioning properly [2]. Biofilms formed on intravascular catheters or central lines are recognized to be the most common cause of hospital acquired bloodstream infections [7]
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