A pursuit of Staphylococcus aureus continues: a role of persister cells

Chang, JuOae; Lee, Rho-Eun; Lee, Wonsik

doi:10.1007/s12272-020-01246-x

Cited by 43 publications

(36 citation statements)

References 62 publications

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“…Another particular trait of S. aureus that makes it notoriously difficult to combat in the clinical setting is phenotypic heterogeneity. An example of this is the phenomenon of persister cells, where sub-populations of S. aureus gain a resistance phenotype against antibiotic treatment resulting from arrested growth [ 10 ]. Persister cells may be generated in numerous ways, one of which is the formation of Small Colony Variants (SCVs) that are characterized by auxotrophy for various compounds involved in the electron transport chain and slow growth, allowing them to escape the effects of many antibiotics [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

Gor

Morikawa

2021

Microorganisms

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Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field.

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Section: Introductionmentioning

confidence: 99%

No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

Gor

Morikawa

2021

Microorganisms

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“…When the body has low resistance or deep wounds, S. aureus easily invades and causes infection. Infection with S. aureus during hospital surgery easily causes pneumonia, pseudomembranous enteritis, pericarditis, and even systemic infections such as sepsis [27]. However, S. aureus is resistant to the currently available antibiotics, so the existing antibiotic drugs cannot meet the treatment needs.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library

Zheng

Liao

et al. 2021

Molecules

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Staphylococcus aureus is an opportunistic pathogen that can cause fatal bacterial infections. MurD catalyzes the formation of peptide bond between UDP-N-acetylehyl-l-alanine and d-glutamic acid, which plays an important role in the synthesis of peptidoglycan and the formation of cell wall by S. aureus. Because S. aureus is resistant to most existing antibiotics, it is necessary to develop new inhibitors. In this study, Schrodinger 11.5 Prime homology modeling was selected to prepare the protein model of MurD enzyme, and its structure was optimized. We used a virtual screening program and similarity screening to screen 47163 compounds from three marine natural product libraries to explore new inhibitors of S. aureus. ADME provides analysis of the physicochemical properties of the best performing compounds during the screening process. To determine the stability of the docking effect, a 100 ns molecular dynamics was performed to verify how tightly the compound was bound to the protein. By docking analysis and molecular dynamics analysis, both 46604 and 46608 have strong interaction with the docking pocket, have good pharmacological properties, and maintain stable conformation with the target protein, so they have a chance to become drugs for S. aureus. Through virtual screening, similarity screening, ADME study and molecular dynamics simulation, 46604 and 46608 were selected as potential drug candidates for S. aureus.

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“…SCVs are defined as slow-growing pin-prick-sized colonies that are less sensitive to antibiotic treatments compared to wildtype pathogens and can revert to a normal phonotype after stress removal [97]. Since the first report about associations between SCVs and persistent infection in 1995 [98], researchers have found that SCVs exist in a wide range of bacteria and are linked to several chronic diseases [99]. In addition, SCVs can promote pathogenicity by promoting biofilm formation [81], presumably facilitated by overexpressing adhesins [100] and by impairing host immunity via necroptosis induction [101].…”

Section: Small Colony Variantsmentioning

confidence: 99%

“…SCVs form in Salmonella planktonic and biofilm cultures when exposed to a high concentration of ciprofloxacin and ceftazidime [106]. Moreover, the formation of SCVs is recognized as part of persistent Salmonella [99] infection. Such SCVs, localized within host cells, can last for several weeks and contribute to a relapse of infection.…”

Section: Small Colony Variantsmentioning

confidence: 99%

Bacterial Persister-Cells and Spores in the Food Chain: Their Potential Inactivation by Antimicrobial Peptides (AMPs)

Liu

Brul

Zaat

2020

IJMS

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The occurrence of bacterial pathogens in the food chain has caused a severe impact on public health and welfare in both developing and developed countries. Moreover, the existence of antimicrobial-tolerant persisting morphotypes of these pathogens including both persister-cells as well as bacterial spores contributes to difficulty in elimination and in recurrent infection. Therefore, comprehensive understanding of the behavior of these persisting bacterial forms in their environmental niche and upon infection of humans is necessary. Since traditional antimicrobials fail to kill persisters and spores due to their (extremely) low metabolic activities, antimicrobial peptides (AMPs) have been intensively investigated as one of the most promising strategies against these persisting bacterial forms, showing high efficacy of inactivation. In addition, AMP-based foodborne pathogen detection and prevention of infection has made significant progress. This review focuses on recent research on common bacterial pathogens in the food chain, their persisting morphotypes, and on AMP-based solutions. Challenges in research and application of AMPs are described.

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A pursuit of Staphylococcus aureus continues: a role of persister cells

Cited by 43 publications

References 62 publications

No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

Identification of Potential Inhibitors of MurD Enzyme of Staphylococcus aureus from a Marine Natural Product Library

Bacterial Persister-Cells and Spores in the Food Chain: Their Potential Inactivation by Antimicrobial Peptides (AMPs)

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