Abstract
Klebsiella species are regarded as terrifying pathogens that threaten different healthcare systems. These pathogens possess a variety of virulence factors which markedly account for their pathogenicity. Three virulence factors (capsule formation, hypermucoviscosity and biofilm formation) were screened, phenotypically and genotypically, among selected Egyptian Klebsiella clinical isolates. Two safe edible agents, clove oil and citric acid, were tested for their effect on bacterial capsules using the Anthony capsular staining method and the transmission electron microscopy. The antibiotic-resistance modifying activity of both agents was studied against selected troublesome isolates showing resistance to amikacin, meropenem and cefotaxime. Molecular docking of citric acid and eugenol with NDM-1, as well as the docking of citric acid with AAC(6′)-Ib and CTX-M-15 were carried out to explain the resistance modifying activity of the tested agents. Capsule formation was the most prominent virulence factor that was detected in all isolates. Both citric acid and clove oil could effectively reduce the size of the formed bacterial capsules. Citric acid showed promising synergistic effects when combined with the studied antibiotics against all the tested isolates. However, clove oil showed a synergistic effect only against 50% of the tested isolates when combined with meropenem. Relying on their binding efficiency mode obtained from molecular docking studies, the tested agents were recognized as promising inhibitors of the studied enzymes. In conclusion, both citric acid and clove oil are auspicious anti-virulence and resistance-modifying agents that can be combined with conventional antibiotics to combat virulent and multidrug resistant Klebsiella isolates.
Highlights
Klebsiella sp. continue to represent a real threat and fear in different healthcare systems as they frequently result in numerous nosocomial infections and are commonly associated with elevated morbidity and mortality rates (Pereira and Vanetti, 2015)
Both citric acid and clove oil are auspicious anti-virulence and resistance-modifying agents that can be combined with conventional antibiotics to combat virulent and multidrug resistant Klebsiella isolates
Depending on the results of the experiment of the antibiotic-resistance modifying activity, we studied the molecular docking of each of citric acid with NDM-1 (New Delhi metallo-beta lactamase (NDM): a metallo-β- lactamase capable of hydrolyzing all β- lactams except aztreonam) (Khan et al, 2017), AAC(6′)-Ib (Aminoglycoside 6’-N-Acetyltransferase type Ib enzyme mediating resistance to amikacin in Klebsiella) (Chiem et al, 2015) and CTX-M-15 (Farhadi et al, 2017)
Summary
Klebsiella sp. continue to represent a real threat and fear in different healthcare systems as they frequently result in numerous nosocomial infections and are commonly associated with elevated morbidity and mortality rates (Pereira and Vanetti, 2015). Possess diverse virulence factors which significantly participate in their pathogenicity (Podschun and Ullmann, 1998). Klebsiella can develop capsules formed from acidic polysaccharides Such capsules can protect the bacteria from phagocytosis by polymorphonuclear granulocytes. Hypermucoviscosity, characterized by the mucoid appearance of the bacterial colonies, is another prominent virulence factor of Klebsiella (Pereira and Vanetti, 2015; Catalan-Najera et al, 2017), where the hypermucoviscous variants possess an obviously greater amount of sialic acid in their capsular extracts, and have a striking phagocytosis-resistance phenotype (Catalan-Najera et al, 2017). The prevalence of antibiotic-resistant bacteria is a major problem encountered in different healthcare systems worldwide. Scientists have become extremely interested in studying the anti-virulence properties of natural and edible agents as novel therapeutic and anti-infective agents, instead of conventional antibiotics (Asfour, 2017)
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