SdiA Enhanced the Drug Resistance of Cronobacter sakazakii and Suppressed Its Motility, Adhesion and Biofilm Formation

Cheng, Chuansong; Yan, Xiangbin; Liu, Binxiong; Jiang, Tao; Zhou, Ziwen; Guo, Fengting; Zhang, Qianwen; Li, Changcheng; Fang, Ting

doi:10.3389/fmicb.2022.901912

Cited by 12 publications

(3 citation statements)

References 45 publications

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“…Studies such as Pacheco et al (2021) and Ahmed et al (2021) have validated the role of SdiA in the production of QS autoinducers in K. pneumoniae and other Enterobacteriaceae, as noticed in enterohemorrhagic Escherichia coli (EHEC), Salmonella enteritica (Cheng et al, 2022). The crystal structure of SdiA has been reported in E. coli as PDB ID: 4LFU, 4LGW, 2AVX (Almeida et al, 2016).…”

Section: Introductionmentioning

confidence: 90%

Molecular modelling of SdiA protein by selected flavonoid and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

Adeosun

Baloyi

Aljoundi

et al. 2022

Journal of Biomolecular Structure and Dynamics

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Klebsiella pneumoniae is one of the perturbing multidrug resistant (MDR) and ESKAPE pathogens contributing to the mounting morbidity, mortality and extended rate of hospitalization. Its virulence, often regulated by quorum sensing (QS) reinforces the need to explore alternative and prospective antivirulence agents, relatively from plants secondary metabolites. Computer aided drug discovery using molecular modelling techniques offers advantage to investigate prospective drugs to combat MDR pathogens. Thus, this study employed virtual screening of selected terpenes and flavonoids from medicinal plants to interrupt the QS associated SdiA protein in K. pneumoniae to attenuate its virulence. 4LFU was used as a template to model the structure of SdiA. ProCheck, Verify3D, Ramachandran plot scores, and ProSA-Web all attested to the model's good quality. Since SdiA protein in K. pneumoniae leads to the expression of virulence, 31 prospective bioactive compounds were docked for antagonistic potential. The stability of the protein-ligand complex, atomic motions and inter-atomic interactions were further investigated through molecular dynamics simulations (MDS) at 100 ns production runs. The binding free energy was estimated using the molecular mechanics/poisson-boltzmann surface area (MM/PB-SA). Furthermore, the drug-likeness properties of the studied compounds were validated. Docking studies showed phytol possesses the highest binding affinity (−9.205 kcal/mol) while glycitein had −9.752 kcal/mol highest docking score. The MDS of the protein in complex with the best-docked compounds revealed phytol with the highest binding energy of −44.2625 kcal/mol, a low root-mean-square deviation (RMSD) value of 1.54 Å and rootmean-square fluctuation (RMSF) score of 1.78 Å. Analysis of the drug-likeness properties prediction and bioavailability of these compounds revealed their conformed activity to lipinski's rules with bioavailability scores of 0.55 F. The studied terpenes and flavonoids compounds effectively thwart SdiA protein, therefore regulate inter-or intra cellular communication and associated in virulence Enterobacteriaceae, serving as prospective antivirulence drugs.

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Section: Introductionmentioning

confidence: 90%

Molecular modelling of SdiA protein by selected flavonoid and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

Adeosun

Baloyi

Aljoundi

et al. 2022

Journal of Biomolecular Structure and Dynamics

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“…We will test more plasmids for complementation in our future studies examining the additional function of ptsH or other genes in C. sakazakii . We hope that the current findings using the deletion mutant [ 31 , 68 ] could still contribute to our understanding the role of ptsH in C. sakazakii .…”

Section: Discussionmentioning

confidence: 99%

“…In order to determine the impact of ptsH gene in C. sakazakii BAA-894, transcriptomic analysis was performed according to previous studies [ 21 , 31 ]. RNA was purified respectively from the WT strain ( n = 3) and Δ ptsH mutant ( n = 3), in which both strains had been cultured earlier in LB broth with proper antibiotics and grown to an OD 600 of 1.0.…”

Section: Methodsmentioning

confidence: 99%

The Role of ptsH in Stress Adaptation and Virulence in Cronobacter sakazakii BAA-894

Sun

Yang

et al. 2022

Foods

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Cronobacter sakazakii, an emerging foodborne pathogen that was isolated primarily from powdered infant formula, poses an important issue in food safety due to its high stress tolerance and pathogenicity. The Hpr (encoded by ptsH gene) has been shown to regulate carbon metabolism as well as stress response and virulence. However, the functional properties of ptsH in C. sakzakii have not been investigated. In this study, we clarified the role of ptsH in the C. sakzakii stress response and virulence, and explored its possible regulatory mechanism by RNA-seq. Compared with wild-type, the ΔptsH mutant showed a slower growth rate in the log phase but no difference in the stationary phase. Moreover, the resistance to heat stress (65 °C, 55 °C), simulated gastric fluid (pH = 2.5), biofilm formation and adhesion to HT-29 cells of ΔptsH mutant were significantly decreased, whereas the oxidative resistance (1, 5, 10 mM H2O2), osmotic resistance (10%, 15%, 20% NaCl), and superoxide dismutase activity were enhanced. Finally, RNA-seq analysis revealed the sulfur metabolism pathway is significantly upregulated in the ΔptsH mutant, but the bacterial secretion system pathway is dramatically downregulated. The qRT-PCR assay further demonstrated that the ΔptsH mutant has elevated levels of genes that are related to oxidative and osmotic stress (sodA, rpoS, cpxA/R, osmY). This study provides a great understanding of the role of ptsH in diverse stress responses and virulence in C. sakazakii, and it contributes to our understanding of the genetic determinant of stress resistance and pathogenicity of this important foodborne pathogen.

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Biofilm formation and associated gene expression changes in Cronobacter from cereal related samples in China

Lou,

Wu,

Huang

et al. 2024

Food Microbiology

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SdiA Enhanced the Drug Resistance of Cronobacter sakazakii and Suppressed Its Motility, Adhesion and Biofilm Formation

Cited by 12 publications

References 45 publications

Molecular modelling of SdiA protein by selected flavonoid and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

Molecular modelling of SdiA protein by selected flavonoid and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

The Role of ptsH in Stress Adaptation and Virulence in Cronobacter sakazakii BAA-894

Biofilm formation and associated gene expression changes in Cronobacter from cereal related samples in China

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