Antibiotic tolerance in biofilm persister cells of Staphylococcus aureus and expression of toxin-antitoxin system genes

Karimaei, Samira; Aghamir, Seyed Mohammad Kazem; Foroushani, Abbas Rahimi; Pourmand, Mohammad Reza

doi:10.1016/j.micpath.2021.105126

Cited by 18 publications

(12 citation statements)

References 30 publications

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“…RelBE was demonstrated to be essential for M. tuberculosis persistence and upregulated in K. pneumoniae and S. aureus upon antibiotic challenge [14,23,24,34,35]. In E. coli, RelE overexpression enhances persistence towards all the antibiotics tested except mitomycin C [28].…”

Section: Relbementioning

confidence: 99%

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Bacterial survivors: evaluating the mechanisms of antibiotic persistence

Shi¹,

Zarkan

2022

Microbiology

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Bacteria withstand antibiotic onslaughts by employing a variety of strategies, one of which is persistence. Persistence occurs in a bacterial population where a subpopulation of cells (persisters) survives antibiotic treatment and can regrow in a drug-free environment. Persisters may cause the recalcitrance of infectious diseases and can be a stepping stone to antibiotic resistance, so understanding persistence mechanisms is critical for therapeutic applications. However, current understanding of persistence is pervaded by paradoxes that stymie research progress, and many aspects of this cellular state remain elusive. In this review, we summarize the putative persister mechanisms, including toxin–antitoxin modules, quorum sensing, indole signalling and epigenetics, as well as the reasons behind the inconsistent body of evidence. We highlight present limitations in the field and underscore a clinical context that is frequently neglected, in the hope of supporting future researchers in examining clinically important persister mechanisms.

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Section: Relbementioning

confidence: 99%

“…Moreover, it has been indicated that MazEF is independent of (p)ppGpp [32,44]. In S. aureus, ΔmazF represses persistence in biofilms and some planktonic cultures, and mazEF is upregulated in both S. aureus and K. pneumoniae upon antibiotic treatments [24,34,35,52].…”

Section: Mazefmentioning

confidence: 99%

Bacterial survivors: evaluating the mechanisms of antibiotic persistence

Shi¹,

Zarkan

2022

Microbiology

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“…At present, in addition to drug resistance, S. aureus can also form biofilms and persisters on the surface of human tissues and organs or implants, causing chronic infections and non-healing. 5 The biofilm formed by S. aureus is composed of proteins, extracellular polysaccharides (EPS), and some small molecules (such as eDNA), which are conducive to their survival in extreme environments and can greatly limit the diffusion and penetration of commonly used antimicrobials, making them difficult to be completely cured. 6 Now, it was found that S. aureus can produce persisters under the influence of antimicrobials, and S. aureus biofilms also contain a large number of persisters, which are resistant to antimicrobials through complex dormancy mechanisms, resulting in repeated infections and difficulty to treat.…”

Section: ■ Introductionmentioning

confidence: 99%

“…6 Now, it was found that S. aureus can produce persisters under the influence of antimicrobials, and S. aureus biofilms also contain a large number of persisters, which are resistant to antimicrobials through complex dormancy mechanisms, resulting in repeated infections and difficulty to treat. 5,7 Thus, now, it remains critical to explore new antimicrobials with an inhibitory effect on the biofilm formation and persisters of S. aureus. 8 However, the development of new antimicrobials often requires a long time, high investment costs, and huge risks.…”

Section: ■ Introductionmentioning

confidence: 99%

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In Vitro Inhibition of Growth, Biofilm Formation, and Persisters of Staphylococcus aureus by Pinaverium Bromide

et al. 2023

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Biofilm or persister cells formed by Staphylococcus aureus are closely related to pathogenicity. However, no antimicrobials exist to inhibit biofilm formation or persister cells induced by S. aureus in clinical practice. This study found that pinaverium bromide had antibacterial activity against S. aureus, with the MIC50/MIC90 at 12.5/25 μM, respectively. Pinaverium bromide (at 4 × MIC) showed a rapid bactericidal effect on S. aureus planktonic cells, and it was more effective (at least 1-log10 cfu/mL) than linezolid, vancomycin, and ampicillin at 4 h of the time-killing test. Pinaverium bromide (at 10 × MIC) significantly inhibited the formation of S. aureus persister cells (at least 3-log10 cfu/mL) than linezolid, vancomycin, and ampicillin at 24, 48, 72, 96, and 120 h of the time-killing test. Biofilm formation and adherent cells of S. aureus isolates were significantly inhibited by pinaverium bromide (at 1/2 or 1/4 × MICs). The fluorescence intensity of the membrane polarity of S. aureus increased with the treatment of pinaverium bromide (≥1 × MIC), and the MICs of pinaverium bromide increased by 4 times with the addition of cell membrane phospholipids, phosphatidyl glycerol and cardiolipin. The cell viabilities of human hepatocellular carcinoma cells HepG2 and Huh7, mouse monocyte-macrophage cells J774, and human hepatic stellate cells LX-2 were slightly inhibited by pinaverium bromide (<50 μM). There were 54 different abundance proteins detected in the pinaverium bromide-treated S. aureus isolate by proteomics analysis, of which 33 proteins increased, whereas 21 proteins decreased. The abundance of superoxide dismutase sodM and ica locus proteins icaA and icaB decreased. While the abundance of global transcriptional regulator spxA and Gamma-hemolysin component B increased. In conclusion, pinaverium bromide had an antibacterial effect on S. aureus and significantly inhibited the formation of biofilm and persister cells of S. aureus.

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