Abstract
Bacterial resistance is caused by several biochemical factors, the formation of biofilm being one of the main causes. This process is triggered by Quorum Sensing (QS), through the production of endogenous molecules, although other substances such as natural products can also do this. In this work, we aimed to determine whether some drugs are involved in the induction of biofilm formation in Klebsiella pneumoniae ATCC 13884, and thus, increase bacterial resistance. For this, the effect of 22 drugs on K. pneumoniae ATCC 13884 growth was determined at sub-plasmatic concentrations; the production of autoinducer lactones was established by HPLC and with a biosensor. The induction of biofilm formation was determined through crystal violet assay at 585 nm in a microplate reader and using urethral catheters. According to the in vitro assays, some drugs were found to induce biofilm formation in K. pneumoniae ATCC 13884. The effect of acetaminophen, hydrochlorothiazide, and progesterone stood out. The first drug caused several changes in the biochemistry of K. pneumoniae ATCC 13884 related to QS: high synthesis of N-hexanoyl-homoserine lactone, increasing bacterial populations by 27% and biofilm formation by 49%, and a more gentamicin resistant biofilm. Furthermore, it increased the colonization area of urethral catheters. Hydrochlorothiazide showed the biggest increase in the induction of biofilm formation of 51%, and progesterone displayed the greatest ability to provoke bacterial mass adherence but had no effects on K. pneumoniae ATCC 13884 bacterial population growth.
Highlights
Antibiotic resistance has become a threat to humanity causing hundreds of thousands of deaths annually and dramatically increasing treatment time and its costs
To determine the effects on quorum sensing mechanisms without interference from the biocide effect, all drugs were analyzed at sub-lethal concentrations; these concentrations were established by finding the concentration range at which bacteria exhibited a growth equal to or higher than that of untreated bacteria
The results demonstrate that some drugs play an active role in biofilm formation in K. pneumoniae
Summary
Antibiotic resistance has become a threat to humanity causing hundreds of thousands of deaths annually and dramatically increasing treatment time and its costs. Klebsiella pneumoniae is the causal agent of several diseases including pneumonia, meningitis, bloodstream infections, and surgical site infections. Some strains are resistant to carbapenem antibiotics, including gentamicin and ciprofloxacin [1], and are the most commonly isolated bacterium from medical devices [2,3]. The World Health Organization classified K. pneumoniae as a critical priority and established the need to promote the search for new antimicrobial agents [4]. K. pneumoniae and other bacteria exhibit Quorum Sensing (QS), a mechanism of bacterial communication, which regulates some biochemical processes in planktonic cells, and biofilms [5]. QS is Antibiotics 2018, 7, 103; doi:10.3390/antibiotics7040103 www.mdpi.com/journal/antibiotics
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