Abstract
Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.
Highlights
Klebsiella spp. are Gram-negative rod shaped bacteria that cause bacterial pneumonia with a high fatality rate if infection remains untreated in the clinical setting [1]
Comparative proteome profiling of K. pneumoniae carbapenemase (KPC)-Klebsiella pneumoniae (KP) treated with CBO
The Pearson correlation values between non-treated and CBOtreated KPC-producing K. pneumoniae (KPC-KP) were of high confidence (0.788 to 0.822), indicating that both the compared groups are of the same organism with no contamination within the samples (Fig 1B)
Summary
Klebsiella spp. are Gram-negative rod shaped bacteria that cause bacterial pneumonia with a high fatality rate if infection remains untreated in the clinical setting [1]. Carbapenems are one of the last lines of antibiotic treatment for severe drug-resistant bacterial infections, and are the treatment of choice for serious infections caused by pathogens carrying the ESBL gene. K. pneumoniae remains the most prevalent bacterial species carrying KPCs, the enzyme has been identified in several other Gramnegative bacilli such as Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica due to horizontal gene transfer [6]. To worsen this issue, KPC-producing K. pneumoniae (KPC-KP) possesses innate antibiotic resistance in the form of an efflux pump, which generally removes the antibiotics that have penetrated the bacterial membrane, from the cytoplasm into the extracellular environment. Membrane permeability can be altered in the presence of antibiotics; preventing the access of antibiotics into the cells, which when coupled to the other mechanisms, enables resistance against higher concentrations of antibiotics [7]
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